Publications

Alturki, R & Gay, V 2019, 'Augmented and Virtual Reality in Mobile Fitness Applications: A Survey' in Applications of Intelligent Technologies in Healthcare, Springer International Publishing, pp. 67-75.
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Obesity is a major issue around the world. It is the main reason for several chronic diseases. Obesity can be stopped by encouraging people to do physical activities and making behaviour intervention regarding lifestyle. Mobile fitness apps are emerging because of the unique features that are provided. They are seen as a vital tool to motivate people suffering from obesity to perform physical activities and make behaviour intervention regarding health and fitness. Augmented reality (AR) and virtual reality (VR) technologies have been used successfully in different kinds of mobile apps. This paper presents a systematic review of some of the most recent AG and VR researches in mobile apps. It discusses the main findings of applying both technologies in different fields of mobile apps. Based on this systematic review, a fitness mobile app for obese individuals that consider both AR and VR technology will be developed.

Ben-Nissan, B, Cazalbou, S & Choi, AH 2019, 'Bioceramics' in Encyclopedia of Biomedical Engineering, Elsevier, pp. 16-33.
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© 2019 Elsevier Inc. All rights reserved. During the last five decades, the capability to engineer or repair new functional tissues by using porous and monolithic ceramics has been a very effective approach to improve the quality of life of patients. Although the use of natural and synthetic materials in body reconstruction and repair goes back to pre-historic times their use have been accelerated considerable during the last few decades in both scientific research and clinical applications. Over the years, many questions concerning their interactions with both hard and soft tissues have been answered with multidisciplinary teams of surgeons, scientists, and engineers. Since 1970s monolithic ceramics such as alumina and partially stabilized zirconia, silicon nitride and sialon ceramics have been used and investigated clinically. Ceramics can be both inert and modified to be bioactive, they have good wettability hence ideal for lubrication under articulating conditions and they have high wear resistance. Although pure zirconia or PSZ is not currently used commercially, alumina and mixtures and their composites with zirconia have been clinically applied widely. In addition a number of clinical glasses such as Bioglass® and other similar compositions are being also used for bone augmentation and restoration in orthopedic, dental and maxillofacial surgery. They have proved to be efficient and effective and in some instances even much better than current metal prostheses. Calcium phosphates, although arguably most important bioceramic in most cases, is used in porous form and it is not covered in this article which was aimed to be on monolithic bioceramics. It is our aim in this article to present the development of these important monolithic bioceramics focusing on the history, synthesis, properties and the current development in clinical applications.

Ben-Nissan, B, Choi, AH & Green, DW 2019, 'Marine Derived Biomaterials for Bone Regeneration and Tissue Engineering: Learning from Nature' in Springer Series in Biomaterials Science and Engineering, Springer Singapore, Switzerland, pp. 51-78.
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Marine structures, biogenic materials, and biomimetic approaches applied to the fabrication of advanced biomaterials and implants are used to address the shortcomings of existing scaffold designs that are biologically un-responsive throughout the regeneration process and lack necessary versatility. Bioactive ceramics converted from biostructures or natural marine-based materials such as corals, sea urchin, sponges and shells are being designed into functional scaffolds that can adapt and evolve to changing environment during regeneration process. They can regulate cell responses at nanostructured surfaces, and as modules for self-assembling by the patient’s own cells and as smart devices that possess tissue specific homing capabilities. These natural structures can be converted to bioactive ceramics such as hydroxyapatite to assist osseointegration. This chapter covers biomimicry, evolution of marine structures, and their specific use and current research on natural materials such as coral, sponge, sea urchin, sponge nacre, and foraminifera as models and raw materials for bioactive bone scaffolding materials and tissue engineering.

Ben-Nissan, B, Choi, AH, Green, DW, Karacan, I, Akyol, S & Cazalbou, S 2019, 'Thoughts and Tribulations on Bioceramics and Marine Structures' in Springer Series in Biomaterials Science and Engineering, Springer Singapore, pp. 1-25.
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Chen, H, Chan, YL, Oliver, BG, Pollock, CA & Saad, S 2019, 'Maternal Smoking and Fetal Brain Outcome: Mechanisms and Possible Solutions' in Preedy, V (ed), Neuroscience of Nicotine, Elsevier, New York, pp. 9-16.
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Although it is well known that maternal cigarette smoke exposure (SE) is detrimental to the health of children, more than 20% of women continue to smoke during pregnancy. Children exposed to maternal smoking in utero have changes in their brain structure and size, often accompanied by cognitive defects. This may be due to increased brain oxidative stress and inflammatory response in the neonatal period, leading to neuron damage in adulthood. The mitochondria, a major source of cellular oxidative stress, are particularly vulnerable to the damage caused by the free radicals they produce. Interestingly, the female offspring seem to be protected by such adverse impact of maternal smoking. This chapter will specifically review the changes in brain inflammation and oxidative stress and the mechanism of mitophagy machinery. Potential therapeutic strategies will be suggested to mitigate the impact of maternal smoking.

Choi, AH & Ben-Nissan, B 2019, 'Marine-Derived Biomaterials for Tissue Engineering Applications' in Marine-Derived Biomaterials for Tissue Engineering Applications, Springer, pp. 99-111.
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This book presents the latest advances in marine structures and related biomaterials for applications in both soft- and hard-tissue engineering, as well as controlled drug delivery.

Coutts, A, Hocking, J & Bilsborough, J 2019, 'Australian Football', Human Kinetics, pp. 393-410.
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DiGiacomo, M, Kochovska, S, Cahill, P, Virdun, C & Phillips, JL 2019, 'Family-Focused Care Span' in Textbook of Palliative Care, Springer International Publishing, pp. 779-797.
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Hansen, T, Saleh, S, Figtree, GA & Gentile, C 2019, 'The Role of Redox Signalling in Cardiovascular Regeneration' in Oxidative Stress in Heart Diseases, Springer Singapore, pp. 19-37.
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© Springer Nature Singapore Pte Ltd. 2019. Cardiovascular disease (CVD) is a major public health problem, particularly in the industrialised world, with diverse causes. Central to these underlying aetiologies is a progressive loss of functional cardiomyocytes, maladaptive remodelling, and resultant cardiac dysfunction. The ageing heart is characterised by perturbations in numerous signalling pathways, impairing its ability to repair and replace injured cardiomyocytes. This is caused at least in part by dysregulation of redox signalling- both in regard to production of reactive oxygen species (ROS), and disruption of cellular protective mechanisms. Cardiac regeneration is one area of particular therapeutic promise, which seeks to ameliorate cardiac function by either (1) direct application of stem cells, (2) modification of molecular signalling pathways to restore the endogenous reparative capacity of the heart, or (3) a combination of these two approaches. Unravelling these molecular and cellular signalling pathways is paramount to unlocking the potential of cardiac regenerative therapies, and theoretically revolutionising the medical management of patients with heart failure. In this chapter, we will review the role of oxidative stress in cardiovascular disease, and the pathophysiological molecular signalling pathways that are involved in the transition from young to ageing heart. We will then provide an overview of the molecular therapies that are used to target these pathways to enhance heart regeneration, future directions involving cellular and novel ‘bio-printing’ based approaches, in addition to current promising clinical trials.

Karacan, I, Ben-Nissan, B & Sinutok, S 2019, 'Marine-Based Calcium Phosphates from Hard Coral and Calcified Algae for Biomedical Applications' in Springer Series in Biomaterials Science and Engineering, Springer Singapore, Switzerland, pp. 137-153.
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The materials that are developed from the different kind of marine organisms have a broad range of properties and characteristics that can explain their potential functions in the biomedical area. Accordingly, new opportunities are created by biomaterials produced from marine-based sources such as calcium phosphate-based bioceramics, composites, and polymers within the biomedical fields such as new drug delivery systems, the design of novel implantable devices, and various applications in tissue engineering. The major aim of this chapter is to explain the importance of marine structures applicable for biomedical applications as well as choosing the appropriate conversion technique in order to obtain designs and structures best suited for their intended use. Therefore, we will highlight various conversion techniques used in the synthesis of calcium phosphate bioceramics from various marine sources such as Tubipora musica , Foraminifera , Porites Hard Corals and Halimeda cylindracea calcified algae, and their biomedical applications in this chapter.

Kulasinghe, A, Warkiani, ME & Punyadeera, C 2019, 'The Isolation and Characterization of Circulating Tumor Cells from Head and Neck Cancer Patient Blood Samples Using Spiral Microfluidic Technology' in Methods in Molecular Biology, Springer New York, pp. 129-136.
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Metastasis is responsible for 90% of cancer-related deaths. The study of circulating tumor cells (CTCs) enables the study of the units of disease responsible for the process of metastasis. While the biology of the primary tissue is relatively known, little is understood about the cells en route to distant sites. Here we describe the isolation of CTCs using the spiral microfluidic technology for the efficient sorting of CTCs from head and neck cancer (HNC) patient blood samples. Furthermore, the molecular characterization of CTCs can aid in stratifying patients for targeted therapy such as immunotherapy, which is having a profound impact in the treatment of metastatic HNC.

Macha, IJ, Ben-Nissan, B, Müller, WH & Cazalbou, S 2019, 'Marine Nanopharmaceuticals for Drug Delivery and Targeting' in Springer Series in Biomaterials Science and Engineering, Springer Singapore, pp. 207-221.
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Oliver, BGG 2019, 'Techniques for detection and research' in Rhinovirus Infections, Elsevier, pp. 265-283.
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© 2019 Elsevier Inc. All rights reserved. This chapter contains practical concepts pertaining to the sampling of the upper and lower airways for human rhinovirus.

Phillips, JL & Currow, D 2019, 'Challenges and Future Directions of Palliative Care' in Textbook of Palliative Care, Springer International Publishing, pp. 111-130.
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Phillips, JL, Virdun, C, Bhattarai, P & Fraser, C 2019, 'Nursing and Palliative Care' in Textbook of Palliative Care, Springer International Publishing, pp. 541-555.
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Rickert, W, Morozova, A, Müller, WH, Vilchevskaya, EN, Ben-Nissan, B & Macha, I 2019, 'Drug Delivery from Polymer-Based Nanopharmaceuticals—Simulations of Selected Diffusion Processes' in Advanced Structured Materials, Springer International Publishing, Switzerland, pp. 207-226.
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© 2019, Springer Nature Switzerland AG. Knowledge about the release behavior of drugs into the human body is essential for correct long-term medication. This paper complements a previous work by providing details of the numerical methods that were used before. Therefore, we shortly explain the experimental setup and state the governing equations. For the numerical solution, two different methods, the finite element method and the finite volume technique, are used. In addition, three different boundary conditions are employed: Dirichlet conditions and classical as well as non-classical convection Robin-type boundary conditions.

Slattery, K & Coutts, AJ 2019, 'The Application of Heat Stress to Team Sports: Football/Soccer, Australian Football and Rugby' in Heat Stress in Sport and Exercise, Springer International Publishing, Switzerland, pp. 181-202.
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This chapter addresses how an added heat stress affects football, Australian football and rugby players during both training and competition. Although these sports are typically played in the cooler winter months, players can still be exposed to hot conditions and this may affect health and performance. It is therefore important to understand how an increased thermal load influences the tactical, technical, physical and psychological constructs that contribute to team sport performance. A review of the literature shows that players modify their physical activity patterns in the heat. This preserves the capacity to maintain technical skills, tactical awareness and perform explosive, high-intensity efforts when required. Nonetheless, players should still be prepared to tolerate the heat from both a performance and health perspective. Practical recommendations for heat acclimatisation, hydration and cooling strategies are provided in line with the current research and each code’s respective heat policy. As the information to date on heat stress in football, Australian football and rugby is based on a relatively small number of studies, further investigation is required to confirm these initial findings, optimise performance in hot conditions and protect players from the adverse effects of heat stress.

Stratton-Powell, AA, Pasko, KM, Lal, S, Brockett, CL & Tipper, JL 2019, 'Biologic Responses to Polyetheretherketone (PEEK) Wear Particles' in Kurtz, SM (ed), PEEK Biomaterials Handbook, Elsevier, Cambridge MA, pp. 367-384.
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The biological response to wear particles is associated with failure and decreased longevity of total joint replacements. Particles in the size range of 0.1–10 μm are considered the most biologically reactive, particularly submicron-sized polymer particles. In bulk form, polyetheretherketone (PEEK) composites are generally considered to be biocompatible. In particulate form, however, the biological response remains unclear, with limited in vitro and in vivo studies defining the cellular reactions to particulates. Only three studies to date have analyzed retrieved periprosthetic human tissue samples to characterize the response to PEEK wear particles. In one study, PEEK particles were observed within macrophages, however, multinucleated giant cells were not present. In two other studies, rod-like carbon particulates and granular-shaped PEEK particles were identified in human tissue by histological analysis. A number of studies have quantified PEEK particles produced from PEEK bearings in joint replacement simulators. The mean particle size (i.e., Feret’s diameter) was reported to be between 0.23 and 2.0 μm, with a range of 0.01–50 μm. In vivo the biological response to PEEK-based particles was reported to be similar to ultrahigh-molecular-weight polyethylene (UHMWPE) particles. Inflammatory cytokine release [e.g., tumor necrosis factor-alpha (TNF)-α] was identified in more than one study without affecting macrophage viability. Only one study has investigated the effects of particle size on cytotoxicity and cytokine release and found unfilled PEEK particles (~ 13 μm) to have a toxic effect; UHMWPE particles in the same size range showed a similar cytotoxic effect. Further research is required to isolate and characterize PEEK-based particles from retrieved human tissue and, to elucidate the effect of particle characteristics, size, and dose on the biological response in both spinal and synovial joint models.

Wadhwa, R, Aggarwal, T, Thapliyal, N, Chellappan, DK, Gupta, G, Gulati, M, Collet, T, Oliver, B, Williams, K, Hansbro, PM, Dua, K & Maurya, PK 2019, 'Nanoparticle-Based Drug Delivery for Chronic Obstructive Pulmonary Disorder and Asthma' in Nanotechnology in Modern Animal Biotechnology, Elsevier, The Netherlands, pp. 59-73.
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Pulmonary diseases including chronic obstructive pulmonary disease (COPD) and asthma affect millions of people all over the world. Conventional treatment methodologies are not sufficient to cure or prevent the disease. With the advent of nanotechnology, drug delivery to specific target site is still challenging, but targeted delivery can be achieved by physiochemical properties of the nanoparticles. Delivery of nanoparticles, liposomes, dendrimers, and others has been extensively studied for successful delivery by inhalation and aerosols. Several factors such as size, density, surface, and physical-chemical properties of nanoparticle are essential to cross airway barriers. In this chapter, different nanoparticle-mediated drug delivery systems have been highlighted along with their applications and toxicity in COPD and asthma.

Wadhwa, R, Shukla, SD, Chellappan, DK, Gupta, G, Collet, T, Hansbro, N, Oliver, B, Williams, K, Hansbro, PM, Dua, K & Maurya, PK 2019, 'Phytotherapy in Inflammatory Lung Diseases: An Emerging Therapeutic Interventional Approach' in Phytochemistry: An in-silico and in-vitro Update, Springer Singapore, Singapore, pp. 331-347.
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Chronic obstructive pulmonary disease (COPD) and asthma are the most common inflammatory respiratory diseases related to an increase in mortality and morbidity. Generally, bronchodilators, ß- agonists, anticholinergics and theophylline used for treatment in these conditions and administered by inhalation for delivery, have localized and systematic effects. The adverse effects are due to pharmacodynamic and pharmacokinetic changes and especially drug-drug and drug-disease interactions. However, phytotherapy is classical and widespread throughout the world for the treatment of ailments. This chapter highlights cellular and molecular mediators involved in COPD and asthma, the shortcomings of current therapies and the emerging need of phytomedicines. Phytomedicine supports respiratory physiology, bronchial action and possesses antioxidants to maintain homeostasis.

Watson, K, Lewis, J & Parker, D 2019, 'Communicating with older people' in Critical Conversations for Patient Safety An Essential Guide for Healthcare Students, pp. 138-150.
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A practical text designed for all health professionals.

Abbasi, QH, Kiourti, A, Heidari, H, He, Y, Warkiani, M & Alomainy, A 2019, 'IEEE Access Special Section Editorial: Wearable and Implantable Devices and Systems', IEEE Access, vol. 7, pp. 139512-139517.
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© 2013 IEEE. Circuit techniques, sensors, antennas and communications systems are envisioned to help build new technologies over the next several years. Advances in the development and implementation of such technologies have already shown us their unique potential in realizing next-generation sensing systems. Applications include wearable consumer electronics, healthcare monitoring systems, and soft robotics, as well as wireless implants. There have been some interesting developments in the areas of circuits and systems, involving studies related to low-power electronics, wireless sensor networks, wearable circuit behaviour, security, real-time monitoring, connectivity of sensors, and Internet of Things (IoT). The direction for the current technology is electronics systems on large area electronics, integrated implantable systems and wearable sensors. So far, the research in the field has focused on materials, new processing techniques and one-off devices, such as diodes and transistors. However, current technology is not sufficient for future electronics to be useful in new applications; a great demand exists to scale up the research towards circuits and systems. Recent developments indicate that, in addition to fabrication technology, special attention should also be given to design, simulation and modeling of electronics, while keeping sensing system integration, power management, and sensors network under consideration.

Ajuyah, P, Hill, M, Ahadi, A, Lu, J, Hutvagner, G & Tran, N 2019, 'MicroRNA (miRNA)-to-miRNA Regulation of Programmed Cell Death 4 (PDCD4)', Molecular and Cellular Biology, vol. 39, no. 18, pp. 1-15.
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Copyright © 2019 Ajuyah et al. The regulation of tumor suppressor genes by microRNAs (miRNAs) is often demonstrated as a one-miRNA-to-one-target relationship. However, given the large number of miRNA sites within a 3= untranslated region (UTR), most targets likely undergo miRNA cooperation or combinatorial action. Programmed cell death 4 (PDCD4), an important tumor suppressor, prevents neoplastic events and is commonly downregulated in cancer. This study investigates the relationship between miRNA 21 (miR-21) and miR-499 in regulating PDCD4. This was explored using miRNA overexpression, mutational analysis of the PDCD4 3= UTR to assess regulation at each miRNA site, and 50% inhibitory concentration (IC50) calculations for combinatorial behavior. We demonstrate that the first miR-499 binding site within PDCD4 is inactive, but the two remaining sites are both required for PDCD4 suppression. Additionally, the binding of miR-21 to PDCD4 influenced miR-499 activity through an increase in its silencing potency and stabilization of its mature form. Furthermore, adjoining miRNA sites more than 35 nucleotides (nt) apart could potentially regulate thousands of 3= UTRs, similar to that observed between miR-21 and miR-499. The regulation of PDCD4 serves as a unique example of regulatory action by multiple miRNAs. This relationship was predicted to occur on thousands of targets and may represent a wider mode of miRNA regulation.

Akyol, S, Ben Nissan, B, Karacan, I, Yetmez, M, Gokce, H, Suggett, DJ & Oktar, FN 2019, 'Morphology, characterization, and conversion of the corals Goniopora spp. and Porites cylindrica to hydroxyapatite', Journal of the Australian Ceramic Society, vol. 55, no. 3, pp. 893-901.
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© 2019, Australian Ceramic Society. The aim of this study is to obtain pure natural hydroxyapatite (HAp) and tricalcium phosphate (TCP) from a Goniopora spp. and from hump coral (Porites cylindrica), both sourced from Australia. Due to the nature of the conversion process, commercial coralline HAp has retained coral or CaCO3, and the structure possesses both nano- and mesopores within the interpore trabeculae resulting in high dissolution rates. To overcome these limitations, a newly patented coral double-conversion technique has been developed. The current technique involves a two-stage application route where in the first-stage complete conversion of coral to pure HAp is achieved. In the second stage, a sol-gel-derived HAp nanocoating is directly applied to cover the meso- and nanopores within the intrapore material, while maintaining the large pores. Here, we specifically investigated the morphological changes and characterized these corals prior to and after conversion. For this purpose, four groups designated as C0, C1, C2, and C3 were used. C0 is Porites, Goniopora, and cylindrica; the original coral is calcium carbonate with aragonite structure that contains proteins and polysaccharides. C1 is coral cleaned under ultrasound in bleach diluted with water. C2 is coral converted to hydroxyapatite (HAp) by hydrothermal treatment method at 200 °C under pressure in the presence of ammonium biphosphate. C3 is obtained by coating C2 with sol-gel alkoxide-derived nanohydroxyapatite to obtain a more bioactive osteoconductive material and improve mechanical properties. All groups were characterized by XRD, EDAX, DTA/TGA, and SEM. The results showed that the biaxial strengths of the C2 and C3 were significantly higher than the original coral. The work also showed the advantages of the hydrothermal conversion method and the effect of the nanocoating which is expected to improve the final bioactivity through microstructural changes of the surfaces.

Alghalayini, A, Garcia, A, Berry, T & Cranfield, C 2019, 'The Use of Tethered Bilayer Lipid Membranes to Identify the Mechanisms of Antimicrobial Peptide Interactions with Lipid Bilayers', Antibiotics, vol. 8, no. 1, pp. 12-12.
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This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, Australia and New Zealand in particular. More and more, tBLMs are replacing liposome release assays, black lipid membranes and patch-clamp electrophysiological techniques because they use fewer reagents, are able to obtain results far more quickly and can provide a uniformity of responses with fewer artefacts. In this work, we describe how tBLM technology can and has been used to identify the actions of numerous antimicrobial agents.

Alturki, R & Gay, V 2019, 'The Development of an Arabic Weight-Loss App Akser Waznk: Qualitative Results', JMIR Formative Research, vol. 3, no. 1, pp. e11785-e11785.
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Argha, A, Su, SW & Celler, BG 2019, 'Control allocation-based fault tolerant control', Automatica, vol. 103, pp. 408-417.
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© 2019 Elsevier Ltd This paper describes a novel scheme for fault tolerant control using a robust optimal control design method. This scheme can also be employed as actuator redundancy management for over-actuated linear systems. In contrast to many existing methods in the literature, this scheme can be applied to systems whose control input matrix cannot be factorised into two matrices whose ranks are equal and less than the minimum of the number of columns and rows of the input matrix. The so-called virtual control, in this scheme, is calculated using a robust ℋ 2 -based feedback design approach constructed to be robust against uncertainties emanating from visibility of the control allocator to the controller and imperfection in the estimated effectiveness gain. Then, using a new control allocation scheme along with a novel Tikhonov-based re-distributor mechanism, the obtained virtual control signal is re-distributed among remaining (redundant or non-faulty) set of actuators. As the proposed scheme is modular-based, it can be employed as a real-time fault tolerant control scheme with no need to reconfigure the controller in the case of actuator faults or failures. The effectiveness of the proposed scheme is demonstrated by a numerical example.

Argha, A, Su, SW & Celler, BG 2019, 'Static output feedback fault tolerant control using control allocation scheme', International Journal of Robust and Nonlinear Control, vol. 29, no. 1, pp. 98-116.
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SummaryThis paper describes two novel schemes for fault tolerant control using robust suboptimal static output feedback design methods. These schemes can also be employed as actuator redundancy management for overactuated uncertain linear systems. In contrast to many existing methods in the literature that assume the control input matrix (i) is not of full‐rank such that it can be factorized into two matrices and (ii) it does not involve uncertainty, these schemes can be applied to systems whose control input matrix cannot be factorized and/or involve uncertainty. The so‐called virtual control, in these schemes, is calculated using suboptimal ‐based static output feedback design schemes constructed to be robust against uncertainties emanating from inherent input matrix uncertainty and visibility of the control allocator to the controller. Then, using two proposed control allocation schemes (fixed and on‐line), the obtained virtual control signal is redistributed among remaining (redundant or nonfaulty) set of actuators. As the proposed schemes are modular‐based, they can be employed as real‐time fault tolerant control schemes with no need to reconfigure the controller in the case of actuator faults or failures. The effectiveness of the proposed schemes is discussed and compared with numerical examples.

Argha, A, Su, SW, Savkin, A & Celler, B 2019, 'A framework for optimal actuator/sensor selection in a control system', International Journal of Control, vol. 92, no. 2, pp. 242-260.
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© 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group. When dealing with large-scale systems, manual selection of a subset of components (sensors/actuators), or equivalently identification of a favourable structure for the controller, that guarantees a certain closed-loop performance, is not very feasible. This paper is dedicated to the problem of concurrent optimal selection of actuators/sensors which can equivalently be considered as the structure identification for the controller. In the context of a multi-channel H 2 dynamic output feedback controller synthesis, we formulate and analyse a framework in which we incorporate two extra terms for penalising the number of actuators and sensors into the variational formulations of controller synthesis problems in order to induce a favourable controller structure. We then develop an explicit scheme as well as an iterative process for the purpose of dealing with the multi-objective problem of controller structure and control law co-design. It is also stressed that the immediate application of the proposed approach lies within the fault accommodation stage of a fault tolerant control scheme. By two numerical examples, we demonstrate the remarkable performance of the proposed approach.

Argha, A, Su, SW, Savkin, A & Celler, B 2019, 'Design of optimal sliding-mode control using partial eigenstructure assignment', International Journal of Control, vol. 92, no. 7, pp. 1511-1523.
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© 2017 Informa UK Limited, trading as Taylor & Francis Group This paper describes a new framework for the design of a sliding surface for a given system while multi-channel (Formula presented.) performances of the closed-loop system are under control. In contrast to most of the current sliding surface design schemes, in this new method, the level of control effort required to maintain sliding is penalised. The proposed method for the design of optimal sliding mode control is implemented in two stages. In the first stage, a state feedback gain is derived using a linear matrix inequality (LMI)-based scheme that can assign a number of the closed-loop eigenvalues to a known value whilst satisfying performance specifications. The sliding function matrix related to the particular state feedback derived in the first stage is obtained in the second stage by using one of the two different methods developed for this goal. The proposed theory is evaluated by using numerical examples including the problem of steady-state output tracking via a state-feedback SMC for flight control.

Argha, A, Su, SW, Zheng, WX & Celler, BG 2019, 'Sliding‐mode fault‐tolerant control using the control allocation scheme', International Journal of Robust and Nonlinear Control, vol. 29, no. 17, pp. 6256-6273.
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SummaryThis paper is devoted to the design of a novel fault‐tolerant control (FTC) using the combination of a robust sliding‐mode control (SMC) strategy and a control allocation (CA) algorithm, referred to as a CA‐based sliding‐mode FTC (SMFTC). The proposed SMFTC can also be considered a modular‐design control strategy. In this approach, first, a high‐level SMC, designed without detailed knowledge of systems' actuators/effectors, commands a vector of virtual control signals to meet the overall control objectives. Then, a CA algorithm distributes the virtual control efforts among the healthy actuators/effectors using the real‐time information obtained from a fault detection and reconstruction mechanism. As the underlying system is not assumed to have a rank‐deficient input matrix, the control allocator module is visible to the SMC module resulting in an uncertainty. Hence, the virtual control, in this scheme, is designed to be robust against uncertainties emanating from the visibility of the control allocator to the controller and imperfections in the estimated effectiveness gain. The proposed CA‐based SMFTC scheme is a unified FTC, which does not need to reconfigure the control system in the case of actuator fault or failure. Additionally, to cope with actuator saturation limits, a novel redistributed pseudoinverse‐based CA mechanism is proposed. The effectiveness of the proposed schemes is discussed with a numerical example.

Argha, A, Wu, J, Su, SW & Celler, BG 2019, 'Blood Pressure Estimation From Beat-by-Beat Time-Domain Features of Oscillometric Waveforms Using Deep-Neural-Network Classification Models', IEEE Access, vol. 7, pp. 113427-113439.
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In general, existing machine learning based approaches, developed for systolic and diastolic blood pressure (SBP and DBP) estimation from oscillometric waveforms (OWs), employ features extracted from the OW envelope (OWE) alone and ignore important beat-by-beat (BBB) features which represent fundamental physical properties of the entire non-invasive blood pressure (NIBP) measurement system. Unlike the existing literature, this paper proposes a novel deep-learning based method for BP estimation trained with BBB time-domain features extracted from OWs. First, we extract six time-domain features from each beat of the OW, relative to the preceding beat. Second, using the extracted BBB features along with the corresponding cuff pressures, we form a feature vector for each OW beat and locate it in one of three different classes, namely pre-systolic (PS), between systolic and diastolic (BSD) and after diastolic (AD). We then devise a deep-belief network (DBN)-deep neural network (DNN) classification model as well as a novel artificial feature extraction method for estimating SBP and DBP from feature vectors extracted from OWs and their corresponding deflation curves. The proposed DBN-DNN classification approach can effectively learn the complex nonlinear relationship between the artificial feature vectors and target classes. The SBP and DBP points are then obtained by mapping the beats at which the network output sequence switches from PS phase to BSD phase and from BSD phase to AD phase, respectively, to the deflation curve. Adopting a 5-fold cross-validation scheme and using a data base of 350 NIBP recordings gave an average mean absolute error of 1.1±2.9 mmHg for SBP and 3.0±5.6 mmHg for DBP relative to reference values. We experimentally show that the proposed DBN-DNN-based classification algorithm trained with BBB time-domain features can outperform traditional deep-learning based methods for BP estimation trained with features extracted only from OWEs.

Arhin, SK, Zhao, J, Ji, X, Shi, C, Tang, J, Gu, Y, Xi, H, Cheng, J, Qu, X, Shi, H, Jin, XL & Lv, JQ 2019, 'Multiple facilitated glucose transporters SLC2As are required for normal mouse preimplantation embryo development', American Journal of Translational Research, vol. 11, no. 6, pp. 3412-3425.
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Background: Glucose metabolism is an essential energy source for mammalian preimplantation embryonic development. Therefore, we aimed to analyze the expression of all 12 known glucose transporters (facilitated solute carrier family 2, Slc2a) during early mouse embryo development. Methods: Gene and protein expression of Slc2a transporters in oocytes and embryos were assessed by the TaqMan gene expression assay and confocal immunofluorescence, respectively. Results: Except for Slc2a2, the other 11 Slc2a transcripts were detected in oocytes. Transcripts of Slc2a1, Slc2a3, Slc2a4, and Slc2a8 were the most enriched and detected in preimplantation embryos. The transcription of other Slc2a isoforms was barely detectable or absent after fertilization; however, they were detected in blastocysts, except for Slc2a10 and Slc2a13. Embryo culture in the simple defined medium caused a reduction in transcription of Slc2a1, Slc2a3, Slc2a4, and Slc2a8 in blastocyst; yet, amino acids partially reversed this impaired transcription of Slc2a1 and Slc2a4. SLC2A1 and SLC2A4 proteins were detected at all embryonic stages with nuclear accumulation in the embryos at the early cleavage stage. SLC2A3 and SLC2A8 were not detected in embryos until the eight-cell stage. The cellular membrane localization of SLC2A1, SLC2A3, and SLC2A8 occurred after compaction and was characterized in blastocysts. SLC2A4 was evenly distributed in the cytoplasm and nuclei without its characteristic membrane localization. Indinavir sulfate (a SLC2A4 inhibitor) decreased the rate of development and prevented glucose utilization in embryos after compaction. These inhibitory activities were partially reversed by exogenous insulin. Conclusion: The results unveil distinct expression patterns of individual Slc2a glucose transporters during early embryo development. Taken together, they provide novel insights into the understanding and management of glucose metabolic infertility in assisted-reproductive technologies (ART).

Ashtari, K, Nazari, H, Ko, H, Tebon, P, Akhshik, M, Akbari, M, Alhosseini, SN, Mozafari, M, Mehravi, B, Soleimani, M, Ardehali, R, Ebrahimi Warkiani, M, Ahadian, S & Khademhosseini, A 2019, 'Electrically conductive nanomaterials for cardiac tissue engineering', Advanced Drug Delivery Reviews, vol. 144, pp. 162-179.
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© 2019 Elsevier B.V. Patient deaths resulting from cardiovascular diseases are increasing across the globe, posing the greatest risk to patients in developed countries. Myocardial infarction, as a result of inadequate blood flow to the myocardium, results in irreversible loss of cardiomyocytes which can lead to heart failure. A sequela of myocardial infarction is scar formation that can alter the normal myocardial architecture and result in arrhythmias. Over the past decade, a myriad of tissue engineering approaches has been developed to fabricate engineered scaffolds for repairing cardiac tissue. This paper highlights the recent application of electrically conductive nanomaterials (carbon and gold-based nanomaterials, and electroactive polymers) to the development of scaffolds for cardiac tissue engineering. Moreover, this work summarizes the effects of these nanomaterials on cardiac cell behavior such as proliferation and migration, as well as cardiomyogenic differentiation in stem cells.

Atto, B, Eapen, MS, Sharma, P, Frey, U, Ammit, AJ, Markos, J, Chia, C, Larby, J, Haug, G, Weber, HC, Mabeza, G, Tristram, S, Myers, S, Geraghty, DP, Flanagan, KL, Hansbro, PM & Sohal, SS 2019, 'New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways', Clinical Science, vol. 133, no. 14, pp. 1663-1703.
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AbstractChronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial–host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen–host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.

Azadi, S, Aboulkheyr Es, H, Razavi Bazaz, S, Thiery, JP, Asadnia, M & Ebrahimi Warkiani, M 2019, 'Upregulation of PD-L1 expression in breast cancer cells through the formation of 3D multicellular cancer aggregates under different chemical and mechanical conditions', Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol. 1866, no. 12, pp. 118526-118526.
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© 2019 Elsevier B.V. Expression of programmed death-ligand 1 (PD-L1) in cancer cells plays an important role in cancer-immune cell interaction. The emerging evidence suggests regulation of PD-L1 expression by several tumor microenvironmental cues. However, the association of PD-L1 expression with chemical and mechanical features of the tumor microenvironment, specifically epidermal growth factor receptor (EGFR) signaling and matrix stiffness, remains elusive. Herein, we determine whether EGFR targeting and substrate stiffness affect the regulation of PD-L1 expression. Breast carcinoma cell lines, MCF7 and MDA-MB-231, were cultured under different conditions targeting EGFR and exposing cells to distinct substrate stiffness to evaluate PD-L1 expression. Furthermore, the ability to form aggregates in short-term culture of breast carcinoma cells and its effect on expression level of PD-L1 was probed. Our results indicated that PD-L1 expression was altered in response to both EGFR inhibition and substrate stiffness. Additionally, a positive association between the formation of multicellular aggregates and PD-L1 expression was observed. MDA-MB-231 cells expressed the highest PD-L1 level on a stiff substrate, while inhibition of EGFR reduced expression of PD-L1. The results suggested that both physical and chemical features of tumor microenvironment regulate PD-L1 expression through alteration of tumor aggregate formation potential. In line with these results, the in-silico study highlighted a positive correlation between PD-L1 expression, EGFR signaling, epithelial to mesenchymal transition related transcription factors (EMT-TFs) and stemness markers in metastatic breast cancer. These findings improve our understanding of regulation of PD-L1 expression by tumor microenvironment leading to evasion of tumor cells from the immune system.

Azadi, S, Tafazzoli‐Shadpour, M, Soleimani, M & Warkiani, ME 2019, 'Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations', Journal of Biomedical Materials Research Part A, vol. 107, no. 8, pp. 1569-1581.
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AbstractTo date, a myriad of strategies has been suggested for targeting the chemical signaling of cancer cells. Also, biomechanical features are gaining much more attention. These features can be used as biomarkers which influence cancer progression. Current approaches on cancer treatment are mainly focused on changing the biochemical signaling of cancer cells, whereas less attention was devoted to their biomechanical properties. Herein, we propose targeting of cancer cell mechanics through the microenvironmental mechanical and chemical cues. As such, we examined the role of substrate stiffness as well as the effect of epidermal growth factor receptor (EGFR) blockade in the cell mechanics. As a mechanical stimulus, stiff and soft polydimethylsiloxane substrates were utilized, while as a chemical stimulus, EGFR blockade was considered. Thus, breast cancer cell lines, MCF7 and MDA‐MB‐231, were cultured among chemical and mechanical groups. The local elasticity of cancer cells was assessed by atomic force microscopy nanoindentation method. Furthermore, we evaluated the effect of mentioned mechanical and chemical treatments on the morphology, actin cytoskeleton structures, and cancer cell migration abilities. The stiffness and migration ability of cancer cells increased by substrate stiffening while Cetuximab treatment demonstrated an elevation in the elastic modulus of cells followed by a reduction in the migration ability. These findings indicate that cancer cell mechanics is modulated not only by the mechanical cues but also by the chemical ones through EGFR signaling pathway. Overall, our results illustrate that manipulation of cell mechanics allows for the possible modulation of tumor cell migration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1569–1581, 2019.

Barakat-Johnson, M, Lai, M, Wand, T, White, K & De Abreu Lourenco, R 2019, 'Costs and consequences of an intervention-based program to reduce hospital-acquired pressure injuries in one health district in Australia', Australian Health Review, vol. 43, no. 5, pp. 516-525.
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Objectives The aims of this study were to determine the costs of hospital-acquired pressure injuries (HAPIs) in one local health district in Australia and compare the costs and consequences of an intervention-based program with current practice to reduce HAPI incidence and prevalence. Methods A retrospective cost–consequence analysis was conducted using HAPI incidence rate per occupied bed days, point prevalence rates, Australian Refined-Diagnosis Related Group (AR-DRG) costs and the costs of the program to reduce the HAPI rate. Data were analysed for two phases: preprogram implementation (1 June 2015–1 June 2016) and postprogram implementation (1 August 2016–31 July 2017). Results The HAPI intervention-based program resulted in a 51.4% reduction in the incidence of HAPI (from 1.46 per occupied bed day in 2014 to 0.71 per occupied bed day in 2017) and a 71.6% reduction in the prevalence of HAPI (from 6.7% in 2014 to 1.9% in 2017). The occurrence of HAPI added an average cost of A$3332 per episode, such that the overall program, including implementation, reduced costs by A$837 387. The greatest cost reduction was due to the cessation of washable and disposable underpads. The largest contributor to the cost of HAPI prevention was for education and training regarding HAPI prevention initiatives. Conclusions The HAPI intervention-based program halved the incidence and substantially reduced the prevalence of HAPI, with a 23.1% cost saving compared with the previous approach to preventing HAPIs. What is known about the topic? HAPIs are costly to the individual, the organisation and health system. The prevention of HAPIs is a priority in Australia. There is limited research on the economic effect of HAPIs and the costs and consequences for hospitals of implementation strategies to reduce their incidence. What does this paper add? This paper informs health policy and decision makers about the costs and consequences for a local...

Barnes-Harris, M, Allgar, V, Booth, S, Currow, D, Hart, S, Phillips, J, Swan, F & Johnson, MJ 2019, 'Battery operated fan and chronic breathlessness: does it help?', BMJ Supportive & Palliative Care, vol. 9, no. 4, pp. 478-481.
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ObjectivesTo examine whether use of a hand-held fan (‘fan’) improves breathlessness and increases physical activity.MethodsA secondary exploratory analysis using pooled data from the fan arms of two feasibility randomised controlled trials in people with chronic breathlessness: (1) fan and activity advice vs activity advice, (2) activity advice alone or with the addition or the ‘calming hand’, or the fan, or both. Descriptive statistics and regression analysis to explore patient characteristics associated with benefit (eg age, sex, diagnosis, general self-efficacy).ResultsForty-one participants were allocated the fan (73 years (IQR 65–76, range 46–88), 59% male, 20 (49%) chronic obstructive pulmonary disease (COPD), three (7%) heart failure, three (7%) cancer). Thirty-five (85%) reported that the fan helped breathing, and 22 (54%) reported increased physical activity.Breathlessness benefit was more likely in older people, those with COPD and those with a carer. However, due to the small sample size none of these findings were statistically significant. Those with COPD were more likely to use the fan than people with other diagnoses (OR 5.94 (95% CI 0.63 to 56.21, p=0.120)).ConclusionsThese exploratory data support that the fan helps chronic breathlessness in most people and adds new data to indicate that the fan is perceived to increase people’s physical activity. There is also a signal of possible particular benefits in people with COPD which is worthy of further study.

Bennett, KJM, Novak, AR, Pluss, MA, Coutts, AJ & Fransen, J 2019, 'Assessing the validity of a video-based decision-making assessment for talent identification in youth soccer', Journal of Science and Medicine in Sport, vol. 22, no. 6, pp. 729-734.
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OBJECTIVES:To investigate the construct and discriminant validity of a video-based decision-making assessment for talent identification in youth soccer. DESIGN:Observational study. METHOD:A total of 328 academy youth soccer players (tier one, tier two, and tier three) from three developmental stages (late childhood, early adolescence, and mid-adolescence) participated in this study. The control group consisted of 59 youth athletes with no soccer experience in the last five years. Players completed a video-based decision-making assessment on an iPad, with response accuracy and response time recorded for various attacking situations (2 vs. 1, 3 vs. 1, 3 vs. 2, 4 vs. 3, and 5 vs. 3). RESULTS:The video-based decision-making assessment showed some construct validity. Response times were significantly faster in early and mid-adolescent players when compared to those in the late childhood group. Furthermore, an overall decline in decision-making performance (i.e. decrease in response accuracy and increase in response time) was observed from the 2 vs. 1 to the 4 vs. 3 situations. The video-based decision-making assessment lacked discriminant validity as minimal differences between academies were evident for response accuracy and response time. Only response accuracy was able to discriminate youth academy soccer players from the control group to some extent. CONCLUSIONS:Coaches and sporting professionals should apply caution when interpreting data from practical, video-based decision-making assessments. There is currently limited conclusive evidence supporting the effectiveness of these assessments for talent identification.

Bhattarai, P, Newton-John, TRO & Phillips, JL 2019, 'Feasibility evaluation of a pain self-management app-based intervention among older people living with arthritic pain: study protocol', Pilot and Feasibility Studies, vol. 5, no. 1, pp. 57-57.
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Background: Optimal management of chronic arthritic pain experienced by older adults involves applying active self-management strategies every day. Cost-effective and innovative strategies to help build older people's pain self-management capability are required. This study protocol is designed to evaluate the feasibility, acceptability, and preliminary outcomes of a pain self-management app among older people living in the community with arthritic pain. Methods/design: This is a phase I feasibility study. A pre-post test study design will be used to trial a freely available pain self-management app named Rheumatoid Arthritis Information Support and Education ('RAISE') for 14 days. Thirty community-dwelling older people living with arthritic pain who use a smartphone will be recruited from (1) various community-based social clubs/organizations/groups or (2) via Facebook groups with potentially high number of older members. In addition, snowballing sampling approach will also be utilized.These participants will trial the RAISE app, which was selected following a systematic evaluation of all available chronic pain apps by the investigator team. A face-to-face or telephone-based meeting will be organized with all consenting participants in order to seek their informed consent, download and set up the intervention app on their mobile device, be provided with app training, and complete the pre-test data (Time 1 (T1)). Participants will be asked to use the RAISE app as desired for 14 days. Post-test data collection (Time 2 (T2)) will occur on day 15. Data collected includes participant's demographic and clinical information, pain scores, pain self-efficacy, and online technology self-efficacy. Participants will be invited to take part in a semi-structured telephone interview at T2 to explore their experiences of using the app.An evaluation of patterns of app use, recruitment, retention, attrition rates, and analysis of the missing data will inform the study a...

Bhimani, A, Bond, D & Sivabalan, P 2019, 'Does greater user representation lead to more user focused standards? An empirical investigation of IASB’s approach to standard setting', Journal of Accounting and Public Policy, vol. 38, no. 2, pp. 65-88.
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© 2019 Elsevier Inc. The International Accounting Standards Board (IASB) has faced calls to act in the interest of users of financial statements given the perception of the greater influence exerted by preparers and professional accounting firm stakeholders. In response, the IASB has, over more than a decade, sought to increase user centricity, adapting its people and processes to more fully engage the views of users. We report on our empirical analysis from the standard setter's perspective of user engagement which is a research objective not documented in the prior literature. Our results draw on interviews conducted with 31 IASB representatives, comprised of 26 staff and 5 Board members representing approximately 60% of IASB's non-support staff as well as publically available archival data. We deploy the Griffiths (1960) citizenship participation framework in reporting on the procedural rigor directed at user utility, to assess IASB's attempt to enhance its perceived relevance (existential enhancement) as a standard setting body. We explain how a “clash” between new user centric practices and the extant practices led to challenges for the IASB in factoring the views of, and acting in the interest of users, as demanded by regulatory authorities. We discuss some of the tensions this has made evident in IASB's objective to function as an effective standard setter. Conceptually, our paper clarifies how more embedded representation modes per Griffith (1960) elicited greater user feedback, but that tensions arose in relation to the IASB's broader objectives to more directly serve users’ interests. Functionally, we offer a more nuanced appreciation for why the IASB might not unilaterally seek to be “user-focused” in the interests of both users and other stakeholders, and in doing so, serve the longer term objectives of accounting standard setting.

Biglari, S, Le, TYL, Tan, RP, Wise, SG, Zambon, A, Codolo, G, De Bernard, M, Warkiani, M, Schindeler, A, Naficy, S, Valtchev, P, Khademhosseini, A & Dehghani, F 2019, 'Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound‐on‐a‐Chip Model', Advanced Healthcare Materials, vol. 8, no. 1, pp. 1801307-1801307.
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AbstractConsiderable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost‐effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs). The wound‐on‐chip model consists of three interconnecting channels and is able to simulate wound inflammation by adding tumor necrosis factor alpha (TNF‐α) or by triculturing with macrophages. Both the approaches significantly increase IL‐1β, IL‐6, IL‐8 in the supernatant (p < 0.05), and increases in cytokine levels are attenuated by cotreatment with an anti‐inflammatory agent, Dexamethasone. Incorporation of M1 and M2 macrophages cocultured with fibroblasts and HUVECs leads to a stimulation of cytokine production as well as vascular structure formation, particularly with M2 macrophages. In summary, this wound‐on‐chip system can be used to model the paracrine component of the early inflammatory phase of wound healing and has the potential for the screening of anti‐inflammatory compounds.

Bliuc, D, Tran, T, van Geel, T, Adachi, JD, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, Josse, R, Kaiser, S, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV & Center, JR 2019, 'Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis', Journal of Bone and Mineral Research, vol. 34, no. 11, pp. 2001-2011.
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ABSTRACT Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39–0.96] and 1.35 [95% CI 0.86–2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%–84%) of the nBP association with mortality was related to a redu...

Bliuc, D, Tran, T, van Geel, T, Adachi, JD, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, Josse, RG, Kaiser, S, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV & Center, JR 2019, 'Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study', Osteoporosis International, vol. 30, no. 4, pp. 817-828.
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© 2019, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Introduction: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. Methods: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. Results: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48–0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66–1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031–0.70)] for n-BP vs. etidronate]. Conclusion: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonat...

Bonou, SAS, Sagbo, E, Aubry, C, Charvillat, C, Ben-Nissan, B & Cazalbou, S 2019, 'Conversion of snail shells (Achatina achatina) acclimatized in Benin to calcium phosphate for medical and engineering use', Journal of the Australian Ceramic Society, vol. 55, no. 4, pp. 1177-1186.
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Bozier, J, Rutting, S, Xenaki, D, Peters, M, Adcock, I & Oliver, BG 2019, 'Heightened response to e-cigarettes in COPD', ERJ Open Research, vol. 5, no. 1, pp. 00192-2018.
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E-cigarettes induce greater inflammatory mediators from COPD lung cells; therefore, the risks of e-cigarette use in COPD might be greater than in people without COPD http://ow.ly/xmnN30nzDhX.

Bradbury, P, Patel, BS, Cidem, A, Nader, CP, Oliver, BG & Ammit, AJ 2019, 'Prostaglandin E2, but not cAMP nor β2-agonists, induce tristetraprolin (TTP) in human airway smooth muscle cells', Inflammation Research, vol. 68, no. 5, pp. 369-377.
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© 2019, Springer Nature Switzerland AG. Tristetraprolin (TTP) is an anti-inflammatory molecule known to post-transcriptionally regulate cytokine production and is, therefore, an attractive drug target for chronic respiratory diseases driven by inflammation, such as asthma and chronic obstructive pulmonary disease. Our recent in vitro studies in primary human airway smooth (ASM) cells have confirmed the essential anti-inflammatory role played by TTP as a critical partner in a cytokine regulatory network. However, several unanswered questions remain. While prior in vitro studies have suggested that TTP is regulated in a cAMP-mediated manner, raising the possibility that this may be one of the ways in which β2-agonists achieve beneficial effects beyond bronchodilation, the impact of β2-agonists on ASM cells is unknown. Furthermore, the effect of prostaglandin E2 (PGE2) on TTP expression in ASM cells has not been reported. We address this herein and reveal, for the first time, that TTP is not regulated by cAMP-activating agents nor following treatment with long-acting β2-agonists. However, PGE2 does induce TTP mRNA expression and protein upregulation in ASM cells. Although the underlying mechanism of action remains undefined, we can confirm that PGE2-induced TTP upregulation is not mediated via cAMP, or EP2/EP4 receptor activation, and occurred in a manner independent of the p38 MAPK-mediated pathway. Taken together, these data confirm that β2-agonists do not upregulate TTP in human ASM cells and indicate that another way in which PGE2 may achieve beneficial effects in asthma and COPD may be via upregulation of the master controller of inflammation—TTP.

Bradbury, P, Rumzhum, NN & Ammit, AJ 2019, 'EP₂ and EP₄ receptor antagonists: Impact on cytokine production and β₂‐adrenergic receptor desensitization in human airway smooth muscle', Journal of Cellular Physiology, vol. 234, no. 7, pp. 11070-11077.
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AbstractProstaglandin E2 (PGE2) is a key prostanoid known to have both proinflammatory and anti‐inflammatory impact in the context of chronic respiratory diseases. We hypothesize that these opposing effects may be the result of different prostanoid E (EP) receptor‐mediated signaling pathways. In this study, we focus on two of the four EP receptors, EP2 and EP4, as they are known to induce cyclic adenosine monophosphate (cAMP)‐dependent signaling pathways. Using primary human airway smooth muscle (ASM) cells, we first focussed on the PGE2‐induced production of two cAMP‐dependent proinflammatory mediators: interleukin 6 (IL‐6) and cyclo‐oxygenase 2 production. We show that PGE2‐induced IL‐6 protein secretion occurs via an EP2‐mediated pathway, in a manner independent of receptor‐mediated effects on messenger RNA (mRNA) expression and temporal activation kinetics of the transcription factor cAMP response element binding. Moreover, stimulation of ASM with PGE2 did not establish a positive, receptor‐mediated, feedback loop, as mRNA expression for EP2 and EP4 receptors were not upregulated and receptor antagonists were without effect. Our studies revealed that the EP2, but not the EP4, receptor is responsible for β2‐adrenergic desensitization induced by PGE2. We demonstrate that PGE2‐induced heterologous receptor desensitization responsible for tachyphylaxis to short‐ (salbutamol) or long‐ (formoterol) β2‐agonists (measured by cAMP release) can be reversed by the EP2 receptor antagonist PF‐04418948. Importantly, this study highlights that inhibiting the EP2

Braytee, A, Liu, W, Anaissi, A & Kennedy, PJ 2019, 'Correlated Multi-label Classification with Incomplete Label Space and Class Imbalance', ACM Transactions on Intelligent Systems and Technology, vol. 10, no. 5, pp. 1-26.
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Multi-label classification is defined as the problem of identifying the multiple labels or categories of new observations based on labeled training data. Multi-labeled data has several challenges, including class imbalance, label correlation, incomplete multi-label matrices, and noisy and irrelevant features. In this article, we propose an integrated multi-label classification approach with incomplete label space and class imbalance (ML-CIB) for simultaneously training the multi-label classification model and addressing the aforementioned challenges. The model learns a new label matrix and captures new label correlations, because it is difficult to find a complete label vector for each instance in real-world data. We also propose a label regularization to handle the imbalanced multi-labeled issue in the new label, and l 1 regularization norm is incorporated in the objective function to select the relevant sparse features. A multi-label feature selection (ML-CIB-FS) method is presented as a variant of the proposed ML-CIB to show the efficacy of the proposed method in selecting the relevant features. ML-CIB is formulated as a constrained objective function. We use the accelerated proximal gradient method to solve the proposed optimisation problem. Last, extensive experiments are conducted on 19 regular-scale and large-scale imbalanced multi-labeled datasets. The promising results show that our method significantly outperforms the state-of-the-art.

Breaden, K, Collier, A, Litster, C, Allcroft, P, Currow, DC & Phillips, JL 2019, 'Stigma and the in(visible) perspectives and expectations of home oxygen therapy among people with chronic breathlessness syndrome: A qualitative study', Palliative Medicine, vol. 33, no. 1, pp. 82-90.
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Background: Chronic breathlessness syndrome in the context of advancing disease is distressing for all concerned. Oxygen is commonly prescribed in this setting; however, little is known about the perspectives of breathless people who either are on oxygen or are yet to have it prescribed. Aim: To understand and describe the perspectives and experiences of breathless people towards oxygen use at home. Design: This qualitative study utilised an interpretive description approach using semi-structured interviews and thematic analysis. Setting/participants: A total of 19 people with chronic breathlessness syndrome living in South Australia participated in semi-structured interviews. Participants were divided into sub-groups according to whether they were chronically breathless and (1) not using home oxygen ( n = 6), (2) using funded home oxygen for severe hypoxaemia ( n = 7) and (3) using home oxygen for palliation outside of funding guidelines ( n = 6). Results: Three main themes were identified: (1) managing distress and living with chronic breathlessness syndrome, with or without oxygen, requires a range of self-management strategies; (2) expectations of oxygen use: ‘Not as good as I thought it would be’; and (3) the stigma of using oxygen: the visible and invisible. Conclusion: People living with chronic breathlessness struggle daily with both the progression of the underlying disease and the distressing nature of the syndrome. While oxygen does provide benefit for some people, its use and the perceptions of its use are often associated with both the visible and invisible manifestations of stigma. Clinic...

Brown, P, Tan, A-C, El-Esawi, MA, Liehr, T, Blanck, O, Gladue, DP, Almeida, GMF, Cernava, T, Sorzano, CO, Yeung, AWK, Engel, MS, Chandrasekaran, AR, Muth, T, Staege, MS, Daulatabad, SV, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C-C, Zhang, Z, Cascella, M, Flegel, WA, Goodyear, CS, van Raaij, MJ, Bukowy-Bieryllo, Z, Campana, LG, Kurniawan, NA, Lalaouna, D, Hüttner, FJ, Ammerman, BA, Ehret, F, Cobine, PA, Tan, E-C, Han, H, Xia, W, McCrum, C, Dings, RPM, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, VD, Bengtsson-Palme, J, Bradshaw, W, Grimm, DG, Kumar, N, Martis, E, Prieto, D, Sabnis, SC, Amer, SEDR, Liew, AWC, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, HP, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K-H, Boehme, KA, Brenneisen, P, Brown, JAL, Dalrymple, BP, Harvey, DJ, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, MD, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, OJ, Kauppila, JH, Zhang, X, Echeverría, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuív, PO, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, FV, Klump, H, Kurgan, L, Smith, SS, Terrier, O, Tuttle, N, Ascher, DB, Janga, SC, Schulte, LN, Becker, D, Browngardt, C, Bush, SJ, Gaullier, G, Ide, K, Meseko, C, Werner, GDA, Zaucha, J, Al-Farha, AA, Greenwald, NF, Popoola, SI, Rahman, MS, Xu, J, Yang, SY, Hiroi, N, Alper, OM, Baker, CI, Bitzer, M, Chacko, G, Debrabant, B, Dixon, R, Forano, E, Gilliham, M, Kelly, S, Klempnauer, K-H, Lidbury, BA, Lin, MZ, Lynch, I, Ma, W, Maibach, EW, Mather, DE, Nandakumar, KS, Ohgami, RS, Parchi, P, Tressoldi, P, Xue, Y, Armitage, C, Barraud, P, Chatzitheochari, S, Coelho, LP, Diao, J, Doxey, AC, Gobet, A, Hu, P, Kaiser, S, Mitchell, KM, Salama, MF, Shabalin, IG, Song, H, Stevanovic, D, Yadollahpour, A, Zeng, E, Zinke, K, Alimba, CG, Beyene, TJ, Cao, Z, Chan, SS, Gatchell, M, Kleppe, A, Piotrowski, M, Torga, G, Woldesemayat, AA, Cosacak, MI, Haston, S, Ross, SA, Williams, R, Wong, A, Abramowitz, MK, Effiong, A, Lee, S, Abid, MB, Agarabi, C, Alaux, C, Albrecht, DR, Atkins, GJ, Beck, CR, Bonvin, AMJJ, Bourke, E, Brand, T, Braun, RJ, Bull, JA, Cardoso, P, Carter, D, Delahay, RM, Ducommun, B, Duijf, PHG, Epp, T, Eskelinen, E-L, Fallah, M, Farber, DB, Fernandez-Triana, J, Feyerabend, F, Florio, T, Friebe, M, Furuta, S, Gabrielsen, M, Gruber, J, Grybos, M, Han, Q & et al. 2019, 'Large expert-curated database for benchmarking document similarity detection in biomedical literature search', Database, vol. 2019, pp. 1-66.
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Abstract Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.

Bryant, C, Aleks Lau, KH, Vuckovic, S, Marsh-Wakefield, F, Kruzins, A, McGuire, H, Yang, S, Fazekas de St. Groth, B, Nassif, N, Byrne, SN, Gibson, J, Brown, C, Larsen, S, McCulloch, D, Boyle, R, Joshua, D & Ho, PJ 2019, 'Accumulation of CD69+ Terminal Effector CD8+ T cells occurs in the bone marrow of newly diagnosed Myeloma patients who lack protective clonal Vb expanded cytotoxic T cells', Clinical Lymphoma Myeloma and Leukemia, vol. 19, no. 10, pp. e29-e29.
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Bulsara, SM, Wainberg, ML, Audet, CM & Newton-John, TRO 2019, 'Retention in HIV Care in Australia: The Perspectives of Clinicians and Clients, and the Impact of Medical and Psychosocial Comorbidity', AIDS Patient Care and STDs, vol. 33, no. 10, pp. 415-424.
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© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019. Significant advances in our understanding and treatment of HIV have led to improvements in the medical management of the illness, as HIV infection has evolved from an acute to a chronic illness. Increasing our understanding of the medical and/or psychosocial comorbidities, which can interact to determine 'clinical complexity' and impact HIV management, will further strengthen this process. Retention in care is a critical step of the HIV Treatment Cascade, which facilitates effective management of these comorbidities and their impact on HIV medical management. This study sought to build on literature regarding medical and/or psychosocial comorbidity that impacts retention in care, and it often leads to clinically complex presentations, by gaining the perspectives of people living with HIV (PLHIV), and medical and allied health clinicians in the field in Sydney, Australia. A total of 16 clinicians (medical doctors, nurses, clinical psychologists, and social workers) and 14 clients participated in a series of focus groups; they were asked to comment on the perceived barriers to retention and the potential solutions to overcome these. The results indicated a significant degree of overlap between clinician and client perspectives, and they identified 'service-specific factors,' 'logistic/practical factors,' 'medical/physical factors,' and 'psychosocial factors' as potential barriers to retention. Results are reviewed in the context of similarities and differences in perspectives between clinicians and PLHIV, and limitations regarding the generalizability of findings are discussed. The broader context of comorbidity and clinical complexity is also examined.

Chacon, D, Braytee, A, Huang, Y, Thoms, J, Subramanian, S, Sauerland, MC, Bohlander, SK, Braess, J, Wörmann, BJ, Berdel, WE, Hiddemann, W, Gabrys, B, Metzeler, KH, Herold, T, Pimanda, J & Beck, D 2019, 'Prospective Identification of Acute Myeloid Leukemia Patients Who Benefit from Gene-Expression Based Risk Stratification', Blood, vol. 134, no. Supplement_1, pp. 1397-1397.
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Background: Acute myeloid leukemia (AML) is a highly heterogeneous malignancy and risk stratification based on genetic and clinical variables is standard practice. However, current models incorporating these factors accurately predict clinical outcomes for only 64-80% of patients and fail to provide clear treatment guidelines for patients with intermediate genetic risk. A plethora of prognostic gene expression signatures (PGES) have been proposed to improve outcome predictions but none of these have entered routine clinical practice and their role remains uncertain. Methods: To clarify clinical utility, we performed a systematic evaluation of eight highly-cited PGES i.e. Marcucci-7, Ng-17, Li-24, Herold-29, Eppert-LSCR-48, Metzeler-86, Eppert-HSCR-105, and Bullinger-133. We investigated their constituent genes, methodological frameworks and prognostic performance in four cohorts of non-FAB M3 AML patients (n= 1175). All patients received intensive anthracycline and cytarabine based chemotherapy and were part of studies conducted in the United States of America (TCGA), the Netherlands (HOVON) and Germany (AMLCG). Results: There was a minimal overlap of individual genes and component pathways between different PGES and their performance was inconsistent when applied across different patient cohorts. Concerningly, different PGES often assigned the same patient into opposing adverse- or favorable- risk groups (Figure 1A: Rand index analysis; RI=1 if all patients were assigned to equal risk groups and RI =0 if all patients were assigned to different risk groups). Differences in the underlying methodological framework of different PGES and the molecular heterogeneity between AMLs contributed to these low-fidelity risk assignments. However, all PGES consistently assigned a significant subset of patients into the same adverse- or favorable-risk groups (40%-70%; Figure 1B: Principal componen...

Chan, YL, Wang, B, Chen, H, Ho, KF, Cao, J, Hai, G, Jalaludin, B, Herbert, C, Thomas, PS, Saad, S & Oliver, BGG 2019, 'Pulmonary inflammation induced by low-dose particulate matter exposure in mice', American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 317, no. 3, pp. L424-L430.
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Air pollution is a ubiquitous problem and comprises gaseous and particulate matter (PM). Epidemiological studies have clearly shown that exposure to PM is associated with impaired lung function and the development of lung diseases, such as chronic obstructive pulmonary disease and asthma. To understand the mechanisms involved, animal models are often used. However, the majority of such models represent high levels of exposure and are not representative of the exposure levels in less polluted countries, such as Australia. Therefore, in this study, we aimed to determine whether low dose PM10 exposure has any detrimental effect on the lungs. Mice were intranasally exposed to saline or traffic-related PM10 (1μg or 5μg/day) for 3 wk. Bronchoalveolar lavage (BAL) and lung tissue were analyzed. PM10 at 1 μg did not significantly affect inflammatory and mitochondrial markers. At 5 μg, PM10 exposure increased lymphocytes and macrophages in BAL fluid. Increased NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and IL-1β production occurred following PM10 exposure. PM10 (5 μg) exposure reduced mitochondrial antioxidant manganese superoxide (antioxidant defense system) and mitochondrial fusion marker (OPA-1), while it increased fission marker (Drp-1). Autophagy marker light-chain 3 microtubule-associated protein (LC3)-II and phosphorylated-AMPK were reduced, and apoptosis marker (caspase 3) was increased. No significant change of remodeling markers was observed. In conclusion, a subchronic low-level exposure to PM can have an adverse effect on lung health, which should be taken into consideration for the planning of roads and residential buildings.

Chen, H & Lim, CED 2019, 'The efficacy of using acupuncture in managing polycystic ovarian syndrome', Current Opinion in Obstetrics & Gynecology, vol. 31, no. 6, pp. 428-432.
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Purpose of review Polycystic ovarian syndrome (PCOS) is a common reproductive disorder, which significantly impairs the fertility of 3–10% of women at reproductive age. It is getting very popular for women with PCOS to seek alternative therapies to treat PCOS, for example, acupuncture. This review examines the currently available evidence from the randomized controlled trial to guide future recommendation on using acupuncture to assist the treatment of PCOS. Recent findings PCOS is manifested by oligo-amenorrhoea, infertility, and hirsutism. The standard treatment of PCOS includes oral pharmacological agents, lifestyle changes, and surgical modalities. Pharmacologically based therapies are only effective in 60% of the patients, which are also associated with different side-effects. As such, acupuncture offered an alternative option. Acupuncture can affect β-endorphin production, which may, in turn, affect gonadotropin-releasing hormone secretion and affecting ovulation and menstrual cycle. Therefore, it is postulated that acupuncture may induce ovulation and restore menstrual cycle via increasing β-endorphin production. Summary Although modern medical science has discovered the action mechanisms underlying how acupuncture may manage the symptoms of PCOS, majority of the trials are small in sample size and lack of consistency in the choice of acupoints. Larger scale trials are needed to provide standardized protocols.

Chen, H, Steele, J, Li, G, Chan, Y, Oliver, B, Saad, S & Machaalani, R 2019, 'E-vapour inhalation – How does it affect memory?', IBRO Reports, vol. 6, pp. S208-S209.
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Chen, X, Chamoli, U, Lapkin, S, Castillo, JV & Diwan, AD 2019, 'Complication rates of different discectomy techniques for the treatment of lumbar disc herniation: a network meta-analysis', European Spine Journal, vol. 28, no. 11, pp. 2588-2601.
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PURPOSE:The aim of this network meta-analysis (NMA) was to compare the complication rates of discectomy/microdiscectomy, percutaneous laser disc decompression (PLDD), percutaneous endoscopic lumbar discectomy (PELD), microendoscopic discectomy (MED), and tubular discectomy for symptomatic lumbar disc herniation (LDH). METHODS:We searched three online databases for randomized controlled trials (RCTs). Overall complication rates, complication rates per general and modified Clavien-Dindo classification schemes, and reoperation rates were considered as primary outcomes. Odds ratio with 95% confidence intervals for direct comparisons and 95% credible intervals for NMA results were reported. Surface under cumulative ranking curve (SUCRA) was used to estimate ranks for each discectomy technique based on the complication rates. RESULTS:In total, 18 RCTs with 2273 patients were included in this study. Our results showed that there was no significant difference in any of the pairwise comparisons. PELD (SUCRA: 0.856) ranked the lowest for overall complication rates. Discectomy/microdiscectomy (SUCRA: 0.599) and PELD (SUCRA: 0.939) ranked the lowest for intraoperative and post-operative complication rates, respectively. Concerning modified Clavien-Dindo classification scheme, PELD (SUCRA: 0.803), MED (SUCRA: 0.730), and PLDD (SUCRA: 0.605) ranked the lowest for the occurrence of type I, II, and III complications, respectively. Tubular discectomy (SUCRA: 0.699) ranked the lowest for reoperation rates. CONCLUSIONS:The results of this NMA suggest that discectomy/microdiscectomy and PELD are the safest procedures for LDH with minimal intraoperative and post-operative complications, respectively. PELD, MED, and PLDD are the safest procedures for LDH in terms of minimal rates for complications necessitating conservative, pharmacological, and surgical treatment, respectively. These slides can be retrieved under Electronic Supplementary Material.

Chepurin, D, Chamoli, U, Sheldrick, K, Lapkin, S, Scott, D, Kuan, J & Diwan, AD 2019, 'Bony stress in the lumbar spine is associated with intervertebral disc degeneration and low back pain: a retrospective case–control MRI study of patients under 25 years of age', European Spine Journal, vol. 28, no. 11, pp. 2470-2477.
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PURPOSE:Abnormal stress in the lumbar vertebra, also known as bony stress, can be a precursor to degenerative changes which may manifest as low back pain (LBP). However, the prevalence of bony stress in the lumbar spine and its relationship with degenerative changes and LBP is unclear. The purpose of this study was to evaluate the prevalence of bony stress in the lumbar spine and its relationship with intervertebral disc (IVD) degeneration, facet osteoarthritis and LBP in patients under 25 years of age. METHODS:A retrospective case-control study of 130 patients under 25 years of age was conducted from a population of 493 patients who had lumbar MRI across three imaging centres over three years. A cohort of 55 consecutive patients with bony stress was identified. A control group of consecutive patients (n = 75) without bony stress was also selected from the population. RESULTS:Bony stress was prevalent in 11% (95% CI [8.4-14.5%]) of patients and was not diagnosed in 36% (95% CI [22-55%]) of these cases. Patients with bony stress had over twofold (OR 2.3, 95% CI [1.1-4.8]) and fivefold (OR 5.3, 95% CI [2.11-13.3]) higher likelihood of having IVD degeneration and LBP, respectively, when compared with the control group. Bony stress was not found to be associated with facet osteoarthritis. CONCLUSION:Bony stress in the lumbar spine was prevalent in 11% of patients under 25 years of age. It was commonly undiagnosed in radiology reports (not reported in 36% of the cases). Being significantly associated and with an increased likelihood of IVD degeneration and LBP, we posit that bony stress is likely a symptomatic and clinically meaningful diagnostic entity in the assessment of LBP. These slides can be retrieved under Electronic Supplementary Material.

Cherk Yong, DO, Saker, SR, Wadhwa, R, Chellappan, DK, Madheswaran, T, Panneerselvam, J, Tambuwala, MM, Bakshi, HA, Kumar, P, Pillay, V, Gupta, G, Oliver, BG, Wark, P, Hsu, A, Hansbro, PM, Dua, K & Zeeshan, F 2019, 'Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma', Journal of Drug Delivery Science and Technology, vol. 54, pp. 101297-101297.
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© 2019 Elsevier B.V. The present study aims to formulate quercetin loaded liquid crystalline nanoparticles (LCN) and surface modified liquid crystalline nanoparticles (sm-LCN) as well as investigate their anti-inflammatory activity in human primary bronchial epithelial cell line (BCi-NS1.1) induced with lipopolysaccharide (LPS). Quercetin LCN were prepared using ultrasonication method. The formulated LCNs and sm-LCNs were characterised in terms of particle size, zeta potential as well as the drug encapsulation efficiency. Furthermore, their morphology and in vitro release profile were also studied. In addition, the anti-inflammatory activity of quercetin LCN and sm-LCNs were evaluated by measuring the concentration of pro-inflammatory markers namely interleukin (IL)-1β, IL-6 and IL-8 in BCI-NS1.1 cell lines via cytometric bead array. The molecular mechanism inherent to the inclusion of quercetin into monoolein nanosystem and surface modification of the nanosystem with chitosan was elucidated via molecular mechanics simulations. Quercetin LCN and sm-LCN significantly (p < 0.05) decreased the production of IL-1β, IL-6 and IL-8 compared to LPS only group. Encapsulation of quercetin into LCN and sm-LCN further enhanced its anti-inflammatory activity compared to quercetin in dimethyl sulfoxide (DMSO). In addition to that, quercetin LCN and sm-LCN also exhibited comparable activity to fluticasone in terms of significantly (p < 0.05) reducing the production of IL-1β and IL-6. Quercetin loaded LCN and sm-LCN could be a potential therapeutic intervention for asthma as they are efficacious in suppressing the production of key pro-inflammatory cytokines associated with the development of asthma.

Clark, K, Allingham, S, Phillips, JL, Brown, L & Currow, DC 2019, 'A Response to: Challenges in Recruiting Patients to a Controlled Feasibility Study of a Drug for Opioid-Induced Constipation: Lessons From the Population With Advanced Cancer', Journal of Pain and Symptom Management, vol. 58, no. 3, pp. e1-e2.
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Clugston, B, Green, B, Phillips, J, Samaraweera, Z, Ceron, C, Gardner, C, Meurk, C & Heffernan, E 2019, 'Interviewing persons with mental illness charged with murder or attempted murder: a retrospective review of police interviews', Psychiatry, Psychology and Law, vol. 26, no. 6, pp. 904-919.
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Individuals with a mental illness may be particularly vulnerable during police interviews. Assessing fitness for police interview is vital for ensuring procedural fairness. This article reports the findings of a retrospective review of 31 police interviews of mentally ill persons charged with murder (n = 18) or attempted murder (n = 13) who appeared before the Queensland Mental Health Court. Police interviews were conducted for all murder and 50% of attempted murder cases. Possible or overt mental illness symptoms were present in all interviews. Symptoms of mental illness were pervasive in 36.7% of interviews, intermittent in 43.3% of interviews and seldom in 20% of interviews. Support persons were present for 9.7% of interviews, and legal representation was not present for any interview. These findings highlight the need to enhance access to support persons during interviews. Intersectoral collaboration between mental health services, forensic medical officers, police, public guardians and the legal sector is needed.

Cohen, R, Fardouly, J, Newton-John, T & Slater, A 2019, '#BoPo on Instagram: An experimental investigation of the effects of viewing body positive content on young women’s mood and body image', New Media & Society, vol. 21, no. 7, pp. 1546-1564.
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Body-positive content on social media aims to challenge mainstream beauty ideals and encourage acceptance and appreciation of all body types. The present study aimed to investigate the effect of viewing body-positive Instagram posts on young women’s mood and body image. Participants were 195 young women (18–30 years old) who were randomly allocated to view either body-positive, thin-ideal, or appearance-neutral Instagram posts. Results showed that brief exposure to body positive posts was associated with improvements in young women’s positive mood, body satisfaction and body appreciation, relative to thin-ideal and appearance-neutral posts. In addition, both thin-ideal and body-positive posts were associated with increased self-objectification relative to appearance-neutral posts. Finally, participants showed favourable attitudes towards the body positive accounts with the majority being willing to follow them in the future. It was concluded that body-positive content may offer a fruitful avenue for improving young women’s body image, although further research is necessary to fully understand the effects on self-objectification.

Cohen, R, Irwin, L, Newton-John, T & Slater, A 2019, '#bodypositivity: A content analysis of body positive accounts on Instagram', Body Image, vol. 29, pp. 47-57.
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© 2019 Elsevier Ltd In the last decade, the body image literature has begun to extend beyond a primary focus on body image disturbances and examine the construct of positive body image. Similarly, “Body positivity” is a growing social media trend that seeks to challenge dominant societal appearance ideals and promote acceptance and appreciation of all bodies and appearances. The present study provides a content analysis of body positive posts on Instagram. A set of 640 Instagram posts sampled from popular body positive accounts were coded for physical appearance-related attributes and central themes featured. Results showed that body positive imagery typically depicted a broad range of body sizes and appearances. Additionally, while a proportion of posts were appearance-focused, the majority of posts conveyed messages aligned with theoretical definitions of positive body image. This study clarifies body positive content on Instagram, as well as highlights points of overlap and distinction from academic principles of positive body image and other appearance-focused social media content. Accordingly, the results offer theoretical and practical implications for future research and prevention efforts.

Condina, MR, Dilmetz, BA, Razavi Bazaz, S, Meneses, J, Ebrahimi Warkiani, M & Hoffmann, P 2019, 'Rapid separation and identification of beer spoilage bacteria by inertial microfluidics and MALDI-TOF mass spectrometry', Lab on a Chip, vol. 19, no. 11, pp. 1961-1970.
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Microfluidics and MALDI-TOF MS is a rapid, high-throughput, and accurate method for the identification of beer spoilage bacteria.

Conte, D, Smith, MR, Santolamazza, F, Favero, TG, Tessitore, A & Coutts, A 2019, 'Reliability, usefulness and construct validity of the Combined Basketball Skill Test (CBST)', Journal of Sports Sciences, vol. 37, no. 11, pp. 1205-1211.
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This study aimed to assess the reliability, usefulness and construct validity of the newly developed Combined Basketball Skill Test (CBST). Fifteen recreational (age = 22.8 ± 4.2 y, stature = 184.8 ± 6.5 cm, body mass = 81.6 ± 9.6 kg, training experience = 9.8 ± 5.3 y) and fifteen semiprofessional (age = 18.9 ± 3.3 y, stature = 190.5 ± 8.1 cm, body mass = 84.2 ± 11.2 kg, training experience = 11.1 ± 3.5 y) players volunteered to participate in this study. Test-retest reliability and usefulness were examined for recreational players, while construct validity was evaluated comparing the two player groups. The CBST is composed of 12 trials and its outcome measures include: completion time (sum of the 12 trial times); penalty time (sum of the times from the 12 trials); performance time (completion time + penalty time) and total number of errors. Relative reliability analysis showed acceptable ICC values (i.e. ≥0.70) in all the studied variables. Absolute reliability analysis showed a CV < 5% for completion (1.6%) and performance (2.0%) time, while a CV >5% is reported for the remaining variables. The usefulness of the test was considered "Marginal" and "Good" when comparing TE values with SWC02 and SWC05, respectively for all the studied variables. Likely and very likely differences were shown between recreational and semiprofessional players in all investigated variables. Results showed that the CBST is reliable, useful to detect moderate changes and valid to assess basketball skills.

Coutts, A 2019, 'Dodging Silver Bullets and Opening Black Boxes: Recommendations for Developing Athlete Monitoring Systems', Journal of Science and Medicine in Sport, vol. 22, pp. S2-S2.
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Crabtree, J & Newton-John, TRO 2019, 'Comparisons and associations between personality, creative potential and achievement in creative, non-creative and early psychosis participants', Psychosis, vol. 11, no. 2, pp. 138-150.
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© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Epidemiological evidence supports common genetic determinants between psychosis spectrum populations and creative individuals. Aspects of personality may contribute to protecting the creative artist from psychosis vulnerability. This study examines the similarities and differences in personality within a sample of early psychosis (EP), creative control (CC) and non-creative control (NCC) participants. Findings indicated that the CC group shared closer personality commonalities with the EP group than with NCC participants, on traits such as Neuroticism, Openness and Impulsive Non-Conformity as well as on variables such as Unusual Experiences, Cognitive Disorganisation and Paranoia/Suspiciousness. However, the CC group may better manage their emotional sensitivity and interpersonal suspiciousness than the EP participants. In separate analyses, CC and EP participants recorded higher creative cognition than NCC participants. Unsurprisingly, the CC group reported significantly higher creative achievement than the EP and NCC samples. Of note, the findings indicate that EP participants recorded significantly higher creative achievement than NCC, suggesting that EP patients demonstrate some capacity for creative cognition and creative achievement. These preliminary findings may encourage further research and promote avenues of treatment for at-risk creative individuals and EP individuals.

Cranfield, CG 2019, 'ABA/ASB Membrane Biophysics session II 2018', Biophysical Reviews, vol. 11, no. 3, pp. 281-282.
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Cui, Y, Poon, J, Miro, JV, Yamazaki, K, Sugimoto, K & Matsubara, T 2019, 'Environment-adaptive interaction primitives through visual context for human–robot motor skill learning', Autonomous Robots, vol. 43, no. 5, pp. 1225-1240.
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© 2018, The Author(s). In situations where robots need to closely co-operate with human partners, consideration of the task combined with partner observation maintains robustness when partner behavior is erratic or ambiguous. This paper documents our approach to capture human–robot interactive skills by combining their demonstrative data with additional environmental parameters automatically derived from observation of task context without the need for heuristic assignment, as an extension to overcome shortcomings of the interaction primitives framework. These parameters reduce the partner observation period required before suitable robot motion can commence, while also enabling success in cases where partner observation alone was inadequate for planning actions suited to the task. Validation in a collaborative object covering exercise with a humanoid robot demonstrate the robustness of our environment-adaptive interaction primitives, when augmented with parameters directly drawn from visual data of the task scene.

Cutler, RL, Torres-Robles, A, Wiecek, E, Drake, B, Van der Linden, N, Benrimoj, SIC & Garcia-Cardenas, V 2019, '<p>Pharmacist-led medication non-adherence intervention: reducing the economic burden placed on the Australian health care system</p>', Patient Preference and Adherence, vol. Volume 13, pp. 853-862.
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© 2019 Cutler et al. Background: Scarcity of prospective medication non-adherence cost measurements for the Australian population with no directly measured estimates makes determining the burden medication non-adherence places on the Australian health care system difficult. This study aims to indirectly estimate the national cost of medication non-adherence in Australia comparing the cost prior to and following a community pharmacy-led intervention. Methods: Retrospective observational study. A de-identified database of dispensing data from 20,335 patients (n=11,257 on rosuvastatin, n=6,797 on irbesartan and n=2,281 on desvenlafaxine) was analyzed and average adherence rate determined through calculation of PDC. Included patients received a pharmacist-led medication adherence intervention and had twelve months dispensing records; six months before and six months after the intervention. The national cost estimate of medication non-adherence in hypertension, dyslipidemia and depression pre-and post-intervention was determined through utilization of disease prevalence and comorbidity, non-adherence rates and per patient disease-specific adherence-related costs. Results: The total national cost of medication non-adherence across three prevalent conditions, hypertension, dyslipidemia and depression was $10.4 billion equating to $517 per adult. Following enrollment in the pharmacist-led intervention medication non-adherence costs per adult decreased $95 saving the Australian health care system and patients $1.9 billion annually. Conclusion: In the absence of a directly measured national cost of medication non-adherence, this estimate demonstrates that pharmacists are ideally placed to improve patient adherence and reduce financial burden placed on the health care system due to non-adherence. Funding of medication adherence programs should be considered by policy and decision makers to ease the current burden and improve patient health outcomes moving forward.

Darcy, S 2019, 'Leisure with impact: research, human rights, and advocacy in a reflective review of a research career', Annals of Leisure Research, vol. 22, no. 3, pp. 273-285.
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© 2019, © 2019 Australia and New Zealand Association of Leisure Studies. This paper presents the key messages from a keynote address I delivered to the 2017 Australia and New Zealand Association of Leisure Studies conference held in Hobart Tasmania, December 2017. In this paper, I reflect on the heuristic learnings from the role of research in addressing critical social issues in leisure and ‘cultural life’. I do so by examining my very deliberate choice to undertake industry-linked research addressing issues involving human rights, social inclusion and giving voice to marginalized groups. As an insider to these voices, I know that research itself does little to address social inequality unless there is a deliberate action by academics to translate research into outcomes through political engagement, challenging organizational practice and communicating the results publicly beyond the paywall of refereed journals. Yet, this type of academic research advocate does not fit easily within neoliberal performance-based metrics that are narrowly defined within disciplinary boundaries of contemporary higher education. As I will explain there are other rich rewards in stepping outside of these boundaries while still doing trustworthy, rigorous, theoretical investigations with high-quality traditional academic outputs. The paper presents a case study of research examining the participation and non-participation of people with disability in sport and active recreation.

Darcy, S, Yerbury, H & Maxwell, H 2019, 'Disability citizenship and digital capital: the case of engagement with a social enterprise telco', Information, Communication & Society, vol. 22, no. 4, pp. 538-553.
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© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. This paper uses as its base a key initiative involving a not-for-profit organisation (NPO), government start-up funding and a social enterprise which evolved through three phases. The purpose of the initiative was the development of a smart phone technology platform for people with disability. The paper’s purpose is to answer questions about the ways in which the mobile technology, seen here as assistive technologies, supported the development of disability citizenship and active citizenship. Data were collected through in-depth interviews conducted at three points in the 13-week programme during which participants with disability received customised support for their phone and training in its use, at no cost. Fifteen participants volunteered to take part in the research project, along with their significant other and service provider. Key themes were identified in the preliminary analysis. Exploring these using Ragnedda’s ([2017]. The third digital divide: A Weberian approach to digital inequalities. Abingdon: Routledge) three levels of digital divide, and Wilson’s ([2006]. The information revolution and developing countries. Cambridge, MA: MIT Press) categories of access allowed a series of philosophical, ethical and human services management questions to emerge, challenging the optimism with which the digital economy is presented as a solution to issues of inequality. Although the mobile technologies were very successful as assistive technologies for some participants, the findings reinforced the potential for such technologies to further entrench aspects of social exclusion. They also identified ways in which the shift in the role of the NPO to social entrepreneurship, and its relationships with government and private enterprise, had the potential to undermine the exercise of disability citizenship by turning participants into consumers.

De Abreu Lourenco, R & Williams, S 2019, 'Health Technology Assessment and Health Care Utilisation in the Management of Early Prostate Cancer', European Urology Focus, vol. 5, no. 2, pp. 134-136.
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© 2018 European Association of Urology Health technology assessment (HTA) is a key tool used to allocate health care funding. A critical aspect of HTA is the performance of economic evaluations that compare the costs and outcomes for competing therapies; these typically rely on data from clinical trials. For early prostate cancer, this represents a challenge, as long-term survival and quality-of-life effects—key outcomes in such evaluations—may require a decade or more of follow-up. Thus, identification of early or intermediate measures of benefit is critical. Systematic reviews of economic evaluations in prostate cancer show that understanding the links between intermediate and final outcomes is important for confidence in assessments of what represents value for money. This highlights the importance of efforts to identify and validate intermediate clinical endpoints for use in determining clinical benefit, and hence value for money, in early prostate cancer. Patient summary: As the costs of providing care rise, the challenge is to ensure that we achieve value for money. In this brief review, we note the importance of clinical trial data in understanding what represents value for money and we highlight current efforts to identify measures that can be used to make decisions on treatment funding sooner.

De Abreu Lourenço, R, Haas, M, Hall, J, Parish, K, Stuart, D & Viney, R 2019, 'My mind is made up: Cancer concern and women’s preferences for contralateral prophylactic mastectomy', European Journal of Cancer Care, vol. 28, no. 4, pp. e13058-e13058.
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© 2019 John Wiley & Sons Ltd The fear of cancer recurrence is cited as a motivator of women's preferences between routine monitoring and contralateral prophylactic mastectomy (CPM) as methods of managing ongoing breast cancer risk. We conducted a discrete choice experiment among a general community sample of women who completed 12 hypothetical choices between routine monitoring and CPM described by aspects of treatment efficacy, safety, cost and involvement in decision-making. Respondents also completed a modified cancer worry question to assess cancer concern. Approximately 57.5% of 464 women always chose one option, typically routine monitoring. The majority (71.5%) reported being concerned about cancer recurrence when completing choice tasks. Latent class analysis identified three groups: preferred routine monitoring; preferred CPM; and “traders” (willing to swap between options). Among traders, women were less likely to choose an option associated with higher risk of recurrence. Women were more likely to choose options associated with less-intrusive monitoring methods and where they were involved in decision-making. Women concerned about cancer recurrence were more likely to choose CPM over monitoring. This study shows that women's preferences about how to manage breast cancer recurrence risk reflect the importance of the associated health effects, experience of care and attitudes to cancer recurrence.

Deplazes, E, White, J, Murphy, C, Cranfield, CG & Garcia, A 2019, 'Competing for the same space: protons and alkali ions at the interface of phospholipid bilayers', Biophysical Reviews, vol. 11, no. 3, pp. 483-490.
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© 2019, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature. Maintaining gradients of solvated protons and alkali metal ions such as Na+ and K+ across membranes is critical for cellular function. Over the last few decades, both the interactions of protons and alkali metal ions with phospholipid membranes have been studied extensively and the reported interactions of these ions with phospholipid headgroups are very similar, yet few studies have investigated the potential interdependence between proton and alkali metal ion binding at the water–lipid interface. In this short review, we discuss the similarities between the proton–membrane and alkali ion–membrane interactions. Such interactions include cation attraction to the phosphate and carbonyl oxygens of the phospholipid headgroups that form strong lipid–ion and lipid–ion–water complexes. We also propose potential mechanisms that may modulate the affinities of these cationic species to the water–phospholipid interfacial oxygen moieties. This review aims to highlight the potential interdependence between protons and alkali metal ions at the membrane surface and encourage a more nuanced understanding of the complex nature of these biologically relevant processes.

Derakhshani, M, Abbaszadeh, H, Movassaghpour, AA, Mehdizadeh, A, Ebrahimi-Warkiani, M & Yousefi, M 2019, 'Strategies for elevating hematopoietic stem cells expansion and engraftment capacity', Life Sciences, vol. 232, pp. 116598-116598.
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© 2019 Elsevier Inc. Hematopoietic stem cells (HSCs) are a rare cell population in adult bone marrow, mobilized peripheral blood, and umbilical cord blood possessing self-renewal and differentiation capability into a full spectrum of blood cells. Bone marrow HSC transplantation has been considered as an ideal option for certain disorders treatment including hematologic diseases, leukemia, immunodeficiency, bone marrow failure syndrome, genetic defects such as thalassemia, sickle cell anemia, autoimmune disease, and certain solid cancers. Ex vivo proliferation of these cells prior to transplantation has been proposed as a potential solution against limited number of stem cells. In such culture process, MSCs have also been shown to exhibit high capacity for secretion of soluble mediators contributing to the principle biological and therapeutic activities of HSCs. In addition, endothelial cells have been introduced to bridge the blood and sub tissues in the bone marrow, as well as, HSCs regeneration induction and survival. Cell culture in the laboratory environment requires cell growth strict control to protect against contamination, symmetrical cell division and optimal conditions for maximum yield. In this regard, microfluidic systems provide culture and analysis capabilities in micro volume scales. Moreover, two-dimensional cultures cannot fully demonstrate extracellular matrix found in different tissues and organs as an abstract representation of three dimensional cell structure. Microfluidic systems can also strongly describe the effects of physical factors such as temperature and pressure on cell behavior.

Domínguez Vila, T, Alén González, E & Darcy, S 2019, 'Accessible tourism online resources: a Northern European perspective', Scandinavian Journal of Hospitality and Tourism, vol. 19, no. 2, pp. 140-156.
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© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Increasing market opportunities have been identified for accessible tourism as a result of improved quality of life. Disabled tourists tend to be loyal, spend more and enjoy longer stays in their destinations, although their behaviour obviously differs from one country to another. This situation is strongly influenced by the welfare policies that determine the disability model implemented and affect the extent to which disabled people are integrated into day-to-day. Northern European countries are regarded as champions in this respect. When disabled people travel, access to information is important. Information is present throughout the tourism process, not only as a communication and marketing channel, but also as a transmitter of experiences. This study seeks to establish whether the policies and regulations that govern disabled people’s access to online tourist information are applied correctly. The official tourism websites of northern European countries were analysed to this end; whereby different patterns were identified regarding their compliance with the Web Content Accessibility Guidelines. The atypical features of Norway’s official tourism website were found to be particularly noteworthy, as were the official tourism websites for Germany and the United Kingdom, two of the countries with the largest market share of accessible tourism.

Eager, D & Hayati, H 2019, 'Additional Injury Prevention Criteria for Impact Attenuation Surfacing Within Children's Playgrounds', ASCE-ASME Journal of Risk and Uncertainty in Engineering Systems, Part B: Mechanical Engineering, vol. 5, no. 1.
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More than four decades have passed since the introduction of safety standards for impact attenuation surfaces (IAS) used in playgrounds. Falls in children's playground are a major source of injuries and IAS is one of the best methods of preventing severe head injuries. However, the ability of IAS in prevention of other types of injuries, such as upper limb fractures, is unclear. Accordingly, in this paper, ten synthetic playground surfaces were tested to examine their performance beyond the collected head injury criterion (HIC) and maximum G-force (Gmax) outputs recommended by ASTM F1292. The aim of this work was to investigate any limitations with current safety criteria and proposing additional criteria to filter hazardous IAS that technically comply with the current 1000 HIC and 200 Gmax thresholds. The proposed new criterion is called the impulse force criterion (If). If combines two important injury predictor characteristics, namely: HIC duration that is time duration of the most severe impact; and the change in momentum that addresses the IAS properties associated with bounce. Additionally, the maximum jerk (Jmax), the bounce, and the IAS absorbed work are presented. HIC, Gmax, If, and Jmax followed similar trends regarding material thickness and drop height. Moreover, the bounce and work done by the IAS on the falling missile at increasing drop heights was similar for all surfaces apart from one viscoelastic foam sample. The results presented in this paper demonstrate the limitations of current safety criteria and should, therefore, assist future research to reduce long-bone injuries in playgrounds.

Ejeian, F, Azadi, S, Razmjou, A, Orooji, Y, Kottapalli, A, Ebrahimi Warkiani, M & Asadnia, M 2019, 'Design and applications of MEMS flow sensors: A review', Sensors and Actuators A: Physical, vol. 295, pp. 483-502.
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© 2019 Elsevier B.V. There is an indispensable need for fluid flow rate and direction sensors in various medical, industrial and environmental applications. Besides the critical demands on sensing range of flow parameters (such as rate, velocity, direction and temperature), the properties of different target gases or liquids to be sensed pose challenges to the development of reliable, inexpensive and low powered sensors. This paper presents an overview of the work done on design and development of Microelectromechanical system (MEMS)-based flow sensors in recent years. In spite of using some similar principles, diverse production methods, analysis strategies, and different sensing materials, MEMS flow sensors can be broadly categorized into three main types, namely thermal sensors, piezoresistive sensors and piezoelectric sensors. Additionally, some key challenges and future prospects for the use of the MEMS flow sensors are discussed briefly.

Ende, JA, Ahmadzad, S, Christensen, JM, Oliver, B, Estephan, T, Alvarado, R, Rimmer, J & Harvey, RJ 2019, 'Isolated respiratory epithelials cell in suspension exhibiting ciliary activity', ASVIDE, vol. 6, pp. 62-62.
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Ende, JA, Ahmadzada, S, Christensen, JM, Oliver, B, Estepha, T, Alvarado, R, Rimmer, J & Harvey, RJ 2019, 'An ALI culture well with well-differentiated respiratory epithelium demonstrating coordinated ciliary activity and mucociliary clearance', ASVIDE, vol. 6, pp. 64-64.
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Ende, JA, Ahmadzada, S, Christensen, JM, Oliver, B, Estephan, T, Alvarado, R, Rimmer, J & Harvey, RJ 2019, 'An ALI culture well exhibiting well-differentiated respiratory epithelium with ciliary activity', ASVIDE, vol. 6, pp. 63-63.
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Ende, JA, Ahmadzada, S, Christensen, JM, Oliver, B, Estephan, T, Alvarado, R, Rimmer, J & Harvey, RJ 2019, 'Environmental responses of virally infected respiratory epithelial cells', Australian Journal of Otolaryngology, vol. 2, no. March, pp. 0-0.
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Background: Rhinovirus, airborne pollution, and allergens are thought to contribute to epithelial dysfunction in chronic airway disease. Objectives were to determine whether these factors act in synergism to induce inflammation and chronic airway disease. Methods: Respiratory mucosa from chronic rhinosinusitis with nasal polyps (CRSwNP) (n=7) or healthy (n=6) patients were cultured at air-liquid interface (ALI) (culture wells n=204). Cells were infected with rhinovirus, then exposed to combinations of vehicle, diesel particulate matter (DPM), and house dust mite (HDM). Ciliary beating frequency (CBF), interleukin (IL)-6 release, and cytotoxicity were assessed by Sisson-Ammons Video Analysis (SAVA) software, flow cytometry, and LDH assays. Results: Compared with healthy cultures, CRSwNP culture groups had lower baseline CBF. The CBF of virally infected ALI cultures was higher than healthy cultures. Challenges tended to impair CBF more in cells that were also virally infected. There was an elevation in IL-6 with viral infection. Challenge combinations did not cause a different IL-6 or CBF response within groups. Conclusions: An inherent mucosal dysfunction and environmental exposures can worsen sinus disease. Synergism in CBF impairment or IL-6 release was not seen.

Facey, JA, Steele, JR, Violi, JP, Mitrovic, SM & Cranfield, C 2019, 'An examination of microcystin-LR accumulation and toxicity using tethered bilayer lipid membranes (tBLMs)', Toxicon, vol. 158, pp. 51-56.
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Microcystin-LR (MC-LR) is a potent cyanobacterial toxin responsible for animal and human poisonings worldwide. MC-LR is found in organisms throughout the foodweb, however there is conjecture regarding whether it biomagnifies. Few studies have investigated how MC-LR interacts with lipid membranes, a determinant of biomagnification potential. We tested whether 1 μM MC-LR irreversibly associates with lipid bilayers or causes the creation of pore defects upon short and long-term exposure. Using tethered bilayer lipid membranes (tBLMs), we observed an increase in membrane conduction in tBLMs, representing an interaction of microcystin-LR with the lipid bilayer and a change in membrane packing properties. However, there were minimal changes in membrane capacitance upon short and long-term exposure, and MC-LR exhibited a rapid off-rate. Upon 24 h exposure to the toxin, no lipophilic multimeric complexes were detected capable of altering the toxin's off-rate. There was no evidence of the creation of new pores. This study demonstrates that MC-LR does not irreversibly imbed itself into lipids membranes after short or long-term exposure and suggests MC-LR does not biomagnify through the food web via lipid storage.

Fan, X, McLaughlin, C, Robinson, C, Ravasini, J, Schelch, K, Johnson, T, Zandwijk, N, Reid, G & George, AM 2019, 'Zeolites ameliorate asbestos toxicity in a transgenic model of malignant mesothelioma', FASEB BioAdvances, vol. 1, no. 9, pp. 550-560.
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Ferguson, C, Hickman, LD, Phillips, J, Newton, PJ, Inglis, SC, Lam, L & Bajorek, BV 2019, 'An mHealth intervention to improve nurses’ atrial fibrillation and anticoagulation knowledge and practice: the EVICOAG study', European Journal of Cardiovascular Nursing, vol. 18, no. 1, pp. 7-15.
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Background: There is a need to improve cardiovascular nurses’ knowledge and practices related to stroke prevention, atrial fibrillation and anticoagulation therapy. Aims: The aim of this study was to evaluate the efficacy of EVICOAG – a novel mHealth, smartphone-based, spaced-learning intervention on nurses’ knowledge of atrial fibrillation and anticoagulation. Methods: Nurses employed in four clinical specialties (neuroscience, stroke, rehabilitation, cardiology) across three hospitals were invited to participate. In this quasi-experimental study, 12 case-based atrial fibrillation and anticoagulation learning scenarios (hosted by an mHealth platform) were delivered to participants’ smartphones over a 6-week period (July–December 2016) using a spaced timing algorithm. Electronic surveys to assess awareness and knowledge were administered pre (T1) and post (T2) intervention. Results: From 74 participants recruited to T1, 40 completed T2. There was a 54% mean improvement in knowledge levels post-intervention. The largest improvement was achieved in domains related to medication interaction and stroke and bleeding risk assessment. Post-intervention, those who completed T2 were significantly more likely to use CHA2DS2-VASc (2.5% vs. 37.5%) and HAS-BLED (2.5% vs. 35%) tools to assess stroke and bleeding risk, respectively ( P<0.01). Conclusion: The EVICOAG intervention improved nurses’ knowledge of atrial fibrillation and anticoagulation, and influenced their uptake and use of stroke and bleeding risk assessment tools in clinical practice. Future research should focus on whether a similar intervention might improve patient-c...

Ferreira, MA, Gamazon, ER, Al-Ejeh, F, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arason, A, Arndt, V, Aronson, KJ, Arun, BK, Asseryanis, E, Azzollini, J, Balmaña, J, Barnes, DR, Barrowdale, D, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Białkowska, K, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Borg, A, Brauch, H, Brenner, H, Broeks, A, Burwinkel, B, Caldés, T, Caligo, MA, Campa, D, Campbell, I, Canzian, F, Carter, J, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Adlard, J, Ahmed, M, Barwell, J, Brady, A, Brewer, C, Cook, J, Davidson, R, Donaldson, A, Eason, J, Eeles, R, Evans, DG, Gregory, H, Hanson, H, Henderson, A, Hodgson, S, Izatt, L, Kennedy, MJ, Lalloo, F, Miller, C, Morrison, PJ, Ong, K-R, Perkins, J, Porteous, ME, Rogers, MT, Side, LE, Snape, K, Walker, L, Harrington, PA, Arnold, N, Auber, B, Bogdanova-Markov, N, Borde, J, Caliebe, A, Ditsch, N, Dworniczak, B, Engert, S, Faust, U, Gehrig, A, Hahnen, E, Hauke, J, Hentschel, J, Herold, N, Honisch, E, Just, W, Kast, K, Larsen, M, Lemke, J, Nguyen, HP, Niederacher, D, Ott, C-E, Platzer, K, Pohl-Rescigno, E, Ramser, J, Rhiem, K, Steinemann, D, Sutter, C, Varon-Mateeva, R, Wang-Gohrke, S, Weber, BHF, Prieur, F, Pujol, P, Sagne, C, Sevenet, N, Sobol, H, Sokolowska, J, Stoppa-Lyonnet, D, Venat-Bouvet, L, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, de la Hoya, M, Dennis, J, Devilee, P, Diez, O, Dörk, T, Dunning, AM, Dwek, M, Eccles, DM, Ejlertsen, B, Ellberg, C, Engel, C, Eriksson, M, Fasching, PA, Fletcher, O, Flyger, H, Friedman, E, Frost, D, Gabrielson, M, Gago-Dominguez, M, Ganz, PA, Gapstur, SM, Garber, J, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Gronwald, J, Guénel, P, Haiman, CA, Hall, P, Hamann, U, He, W, Heyworth, J, Hogervorst, FBL, Hollestelle, A, Hoover, RN, Hopper, JL, Hulick, PJ, Humphreys, K, Imyanitov, EN, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, SC, Marsh, D, Morey, A, Pathmanathan, N, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Heemskerk-Gerritsen, BAM, Rookus, MA, Seynaeve, CM, van der Baan, FH, van der Hout, AH, van der Kolk, LE, van der Luijt, RB, van Deurzen, CHM, van Doorn, HC, van Engelen, K, van Hest, L, van Os, TAM & et al. 2019, 'Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer', Nature Communications, vol. 10, no. 1, p. 1741.
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AbstractGenome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Fetherstonhaugh, DM, Rayner, J-A, Beattie, E, Harrington, A, Jeon, Y-H, Moyle, W, Parker, D & Toye, C 2019, 'BUILDING CAPACITY TO CARE FOR OLDER PEOPLE! HOW IS CARE OF THE OLDER PERSON TAUGHT IN AUSTRALIAN SCHOOLS OF NURSING?', Innovation in Aging, vol. 3, no. Supplement_1, pp. S3-S3.
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Abstract As the Australian population ages the demand for nursing care which focuses on responding to the needs of the older person will increase. Few newly graduated Registered Nurses (RNs) currently enter the aged care workforce and few select a career in caring for older people; yet older people are the largest patient group in most health care environments. This research, conducted by the Australian Hartford Consortium of Gerontological Nursing Excellence (Aus-HCGNE), explored how care of the older person is currently taught in Australian schools of nursing (SoN). The interview guide included questions about: whether care of the older person is taught in separate subjects or integrated across the curriculum; academics’ qualifications; subject content; and aged care clinical placements. The head of each of the 33 Australian schools of nursing was contacted, invited to participate and asked to nominate the appropriate academics (undergraduate/curriculum co-ordinators) who would be the most appropriate person to participate in the interview. These academics were then contacted, written informed consent was obtained, interviews were scheduled and completed. This research is timely given the current Royal Commission into Aged Care Quality and Safety in Australia, one focus of which is nurses in residential aged care in respect to numbers, education and competence. This research will be completed by mid-2019. The results will be fed back to SoN to inform the development of their curricula and the preparation of future RNs who will undoubtably need to be expert in the care of older people across the health sector.

Figlioli, G, Bogliolo, M, Catucci, I, Caleca, L, Lasheras, SV, Pujol, R, Kiiski, JI, Muranen, TA, Barnes, DR, Dennis, J, Michailidou, K, Bolla, MK, Leslie, G, Aalfs, CM, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Adank, MA, Adlard, J, Agata, S, Cadoo, K, Agnarsson, BA, Ahearn, T, Aittomäki, K, Ambrosone, CB, Andrews, L, Anton-Culver, H, Antonenkova, NN, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Asseryanis, E, Auber, B, Auvinen, P, Azzollini, J, Balmaña, J, Barkardottir, RB, Barrowdale, D, Barwell, J, Beane Freeman, LE, Beauparlant, CJ, Beckmann, MW, Behrens, S, Benitez, J, Berger, R, Bermisheva, M, Blanco, AM, Blomqvist, C, Bogdanova, NV, Bojesen, A, Bojesen, SE, Bonanni, B, Borg, A, Brady, AF, Brauch, H, Brenner, H, Brüning, T, Burwinkel, B, Buys, SS, Caldés, T, Caliebe, A, Caligo, MA, Campa, D, Campbell, IG, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Claes, KBM, Clarke, CL, Collavoli, A, Conner, TA, Cox, DG, Cybulski, C, Czene, K, Daly, MB, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dite, GS, Ditsch, N, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Durda, K, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Ellberg, C, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Flyger, H, Foulkes, WD, Friebel, TM, Friedman, E, Gabrielson, M, Gaddam, P, Gago-Dominguez, M, Gao, C, Gapstur, SM, Garber, J, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Gayther, SA, Belotti, M, Bertrand, O, Birot, A-M, Buecher, B, Caputo, S, Dupré, A, Fourme, E, Gauthier-Villars, M, Golmard, L, Le Mentec, M, Moncoutier, V, de Pauw, A, Saule, C, Boutry-Kryza, N, Calender, A, Giraud, S, Léone, M, Bressac-de-Paillerets, B, Caron, O, Guillaud-Bataille, M, Bignon, Y-J, Uhrhammer, N, Bonadona, V, Lasset, C, Berthet, P, Castera, L, Vaur, D, Bourdon, V, Noguès, C, Noguchi, T, Popovici, C, Remenieras, A, Sobol, H, Coupier, I, Pujol, P, Adenis, C, Dumont, A, Révillion, F, Muller, D, Barouk-Simonet, E, Bonnet, F, Bubien, V, Longy, M, Sevenet, N, Gladieff, L, Guimbaud, R, Feillel, V, Toulas, C, Dreyfus, H, Leroux, CD, Peysselon, M, Rebischung, C, Legrand, C, Baurand, A, Bertolone, G, Coron, F, Faivre, L, Jacquot, C, Lizard, S, Kientz, C, Lebrun, M, Prieur, F, Fert-Ferrer, S, Mari, V, Vénat-Bouvet, L, Bézieau, S & et al. 2019, 'The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer', npj Breast Cancer, vol. 5, no. 1.
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AbstractBreast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM

Fischer, T, Hosie, A, Luckett, T, Agar, M & Phillips, J 2019, 'Strategies for Pain Assessment in Adult Patients With Delirium: A Scoping Review', Journal of Pain and Symptom Management, vol. 58, no. 3, pp. 487-502.e11.
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© 2019 American Academy of Hospice and Palliative Medicine Context: Pain and delirium are highly prevalent in the same patient groups. Disturbances in attention, awareness, and cognition are characteristics for delirium and can compromise pain assessment. Objectives: The aim of this review was to examine and map models and understandings of pain and delirium as well as pain assessment instruments and strategies for adult patients with delirium. Methods: A scoping review of all publications that reported on pain assessment in adult patients with delirium was conducted with no time and language constraints, searching Medline, CINAHL, Scopus, Embase, and PsycINFO and systematically assessing for inclusion. Standardized data extraction and a narrative synthesis followed. Results: A total of 90 publications were included in the final analysis. Despite being recommended for practice, no evidence for the use of self-report or behavioral pain assessment instruments in patients with delirium was identified, with the exception of limited evidence for the validity of the Critical Care Pain Observation Tool and Behavioral Pain Scale in delirious intensive care patients. Proxy ratings of pain and comprehensive pain assessment hierarchies were also recommended, but not supported by evidence. Current models and/or understandings of pain and delirium were not applied in most publications. Conclusion: The current literature is insufficient to guide clinical practice in pain assessment in patients with delirium. Future research will be needed to address the validity of existing pain assessment instruments, apply theoretical and conceptual understandings of pain and delirium, and build on prior studies to close evidence gaps.

Fleming, C, Gunawan, C, Golzan, M, Torpy, F, Irga, P & Mcgrath, K 2019, 'Investigating the effects of air pollutant nanoparticles on the onset or progression of Alzheimer's disease', IBRO Reports, vol. 6, pp. S329-S330.
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Fullagar, HHK, McCall, A, Impellizzeri, FM, Favero, T & Coutts, AJ 2019, 'The Translation of Sport Science Research to the Field: A Current Opinion and Overview on the Perceptions of Practitioners, Researchers and Coaches', Sports Medicine, vol. 49, no. 12, pp. 1817-1824.
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© 2019, Springer Nature Switzerland AG. Evidence-based practice (EBP) is the collated integration of practitioner expertise, athlete values and research evidence aimed to optimise the decision-making process surrounding sport performance. Despite the academic interest afforded to sport science research, our knowledge of how this research is applied in elite sport settings is limited. This current opinion examines the existing evidence of the translation of sport science research into the field, with a tailored focus on the current perceptions of practitioners, researchers and coaches. Recent studies show that practitioners and researchers report they ascertain sport science knowledge differently, with coaches preferring personal interactions compared with coaching courses or scientific journals. The limited peer-reviewed research shows that coaches perceive their knowledge is greater in fields such as tactical/technical areas, rather than physical fitness or general conditioning. This likely explains coaches’ greater perceived value in research dedicated to technical and tactical expertise, as well as mental training and skill acquisition. Practitioners place a large emphasis on the need for research in physical fitness areas, which is likely due to their occupational focus. There are many perceived barriers of sport science research application, including funding, time, coach/player/staff ‘buy in’ and research questions that may not apply to the setting. We contend that researchers and practitioners may benefit in producing research, ascertaining knowledge and disseminating findings in alternative methods that better align with coaches’ needs. In addition, educational strategies that focus on real-world context and promote social interaction between coaches, practitioners, organisational personnel and researchers would likely benefit all stakeholders.

Gamble, LD, Purgato, S, Murray, J, Xiao, L, Yu, DMT, Hanssen, KM, Giorgi, FM, Carter, DR, Gifford, AJ, Valli, E, Milazzo, G, Kamili, A, Mayoh, C, Liu, B, Eden, G, Sarraf, S, Allan, S, Di Giacomo, S, Flemming, CL, Russell, AJ, Cheung, BB, Oberthuer, A, London, WB, Fischer, M, Trahair, TN, Fletcher, JI, Marshall, GM, Ziegler, DS, Hogarty, MD, Burns, MR, Perini, G, Norris, MD & Haber, M 2019, 'Inhibition of polyamine synthesis and uptake reduces tumor progression and prolongs survival in mouse models of neuroblastoma', Science Translational Medicine, vol. 11, no. 477.
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MYCN regulates polyamines in neuroblastoma, and combined inhibition of polyamine synthesis and transport has therapeutic effects in mouse models.

Garcia, MV, Luckett, T, Johnson, M, Hutchinson, A, Lal, S & Phillips, JL 2019, 'The roles of dispositional coping style and social support in helping people with respiratory disease cope with a breathlessness crisis', Journal of Advanced Nursing, vol. 75, no. 9, pp. 1953-1965.
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AbstractAimTo explore the role of coping moderators in self‐management of breathlessness crises by people with advanced respiratory disease.DesignA secondary analysis of semi‐structured interview data.MethodsInterviews with patients who had advanced respiratory disease, chronic breathlessness and at least one experience where they considered presenting to Emergency but self‐managed instead (a “near miss”). Participants were recruited from New South Wales, Queensland, Victoria, South Australia or Tasmania. Eligible caregivers were those who contributed to Emergency‐related decision‐making. Interviews were coded inductively and then deductively against the coping moderators social support and dispositional coping style, defined by the Transactional Model of Stress and Coping.ResultsInterviews were conducted between October 2015 ‐ April 2016 with 20 patients and three caregivers. Social networks offered emotional and practical support but also had potential for conflict with patients' ‘hardy’ coping style. Patient hardiness (characterized by a sense of ‘commitment’ and ‘challenge’) promoted a proactive approach to self‐management but made some patients less willing to accept support. Information‐seeking tendencies varied between patients and were sometimes shared with caregivers. An optimistic coping style appeared to be less equivocally beneficial.ConclusionThis study shows that social support and coping style may influence how people self‐manage through their breathlessness crises and identified ways coping moderators can facilitate or hinder effective self‐management.ImpactThis...

Gay, VC, Garcia, JA & Leong, TW 2019, 'Using Asynchronous Exergames to Encourage an Active Ageing Lifestyle: Solitaire Fitness Study Protocol.', Stud Health Technol Inform, vol. 266, pp. 70-75.
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A healthy and active lifestyle can significantly improve the well-being and quality of life; however, some elderly people struggle to stay motivated and engaged with any form of exercise. The project Elaine (Elderly, AI and New Experiences) addresses this problem by seeking to improve the quality of life of the elderly through exergames. Currently, the project explores a novel approach in the field of health informatics called asynchronous exergaming. This approach, a new trend in games in the health domain, allows the elderly to workout at their own pace, and in their own time, with their physical activity linked asynchronously to a game. This paper presents the study protocol for Solitaire Fitness, a new asynchronous exergame developed by the team. The game aims at increasing the motivation of the elderly to engage in physical exercise whilst helping to maintain their cognitive abilities. It also describes the protocol for the trial. The result of this research has the potential to benefit elderly that need nudging to be motivated to exercise, health care providers treating people with sedentary lifestyles and researchers investigating ways to encourage the elderly to exercise.

Gentile, C, Kesteven, S, Wu, J, Bursill, C, Davies, MJ & Figtree, G 2019, 'Abstract 138: A Novel Cellular and Genetic Approach to Investigate the Cardioprotective Role Played by Endothelial Nitric Oxide Synthase in Myocardial Infarction', Circulation Research, vol. 125, no. Suppl_1.
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The loss of regenerative properties in adult cardiomyocytes (CMs) is directly linked to their inability to proliferate. Following an extensive ischaemic event in an aged heart, fibrotic scar formation is the only repair process and eventually heart failure develops. However, molecular and cellular cues in the neonatal heart support that cardiac regeneration is possible in presence of proliferating CMs. Based on previous studies demonstrating that endothelial nitric oxide synthase (eNOS) regulates proliferation in both endothelial cells (ECs) and CMs, we hypothesized that eNOS signaling could play a cardioprotective role. To test our hypothesis, we injected different combinations of co-cultured ECs and CMs in the LV muscle wall of MI mice (permanent LAD ligation). First, injected cells were isolated from either WT or KO eNOS neonatal mice and then co-cultured to form 3D vascularized cardiac spheroids (VCSs), which were eventually transplanted in adult MI mice on the day of the procedure. Control infarcted animals received media-only (vehicle). Other mice received a suspension of co-cultured VCSs in media as follows: i ) WT CMs and ECs; ii ) WT CMs and KO ECs; iii ) KO CMs and WT ECs. Following 28 days, injection of WT cells increased the ejection fraction (EF%) by 20% compared with control animals (61%±4% and 41%±11%, respectively). When eNOS was absent in either CMs or ECs, the EF% was 40%±5% and 46%±2%, respectively, suggesting that the eNOS-mediated protection is dependent on its presence in both cells. Histological analyses confirmed the presence of WT VCSs in MI mice, contributing to a thicker wall thickness compared to vehicle MI mice. No VCSs were observed in the LV wall when KO cells were injected. Therefore, our results strongly suggest that eNOS may play a major role via bo...

Georgevsky, D, Gangoda, SVS & Golzan, SM 2019, 'Postural effects on spontaneous retinal venous pulsations in healthy individuals', Acta Ophthalmologica, vol. 97, no. 6, pp. e839-e843.
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AbstractPurposeTo assess amplitudes of spontaneous retinal venous pulsations (SVP) in three various postures (sitting, supine and lateral decubitus) in healthy individuals.MethodsThirty participants (28 ± 8 years, 25 females) were included in the study. Intraocular pressure (IOP), blood pressure (BP) and SVP's were measured at three different postures using a calibrated Tono‐Pen applanation tonometer, a digital sphygmomanometer, and a custom‐built handheld video ophthalmoscope, respectively. Retinal venous pulsations (SVP) amplitudes were extracted from the retinal videos using a custom written MATLAB algorithm. Mean arterial pressure (MAP = (systolic + 2diastolic)/3) and mean ocular perfusion pressure (MOPP = (2/3 MAP)‐IOP) were also calculated at each posture. A one‐way ANOVA was applied to each parameter to determine any significant difference for the various postural changes.ResultsMean IOP increased (p < 0.0001) and mean SVP decreased (p < 0.0001) from sitting to supine. The mean IOP (mmHg) and SVP (MU; measuring units) in sitting, supine and lateral decubitus were 16.2 ± 2, 19.4 ± 4, 19.8 ± 2 mmHg and 5.8 ± 2, 4.5 ± 2, and 4.7 ± 2 MU, respectively. Mean arterial pressure (MAP) and MOPP also decreased significantly from sitting to supine (p < 0.001, p < 0.001) and sitting to lateral decubitus (p < 0.05, p < 0.01). There were no significant differences between IOP, SVP, MAP or MOPP during a postural modification from supine to lateral decubitus.ConclusionsIn this study, we showed a significant reduction in SVP amplitudes and a significant increase in IOP from sitting to supine position in a healthy young cohort. This supports the rationale to further study such phenomenon in ocul...

Georgevsky, D, Retsas, S, Raoufi, N, Shimoni, O & Golzan, SM 2019, 'A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer’s disease', Translational Neurodegeneration, vol. 8, no. 1, p. 30.
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Abstract Background A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer’s disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age. Methods Electroretinogram (ERG) and optical coherence tomography (OCT) was performed in APP/PS1 and wild type (WT) control mice every 3 months from 3 to 12 months of age. For functional assessment, the a- and b-wave of the ERG, amplitude of oscillatory potentials (OP) and the positive scotopic threshold response (pSTR) were quantified at each time point. For structural assessment, the inner and outer retinal thickness was segmented and measured from OCT scans. Episodic memory was evaluated at 6, 9 and 12 months of age using the novel object recognition test. Amyloid beta (Aβ) distribution in the hippocampus and the retina were visualised at 3, 6 and 12 months of age. Inter- and intra- group analysis was performed to study rate of change for each parameter between the two groups. Results Inter-group analysis revealed a significant difference in b-wave and OPs of APP/PS1 compared to WT controls starting from 3 months (p < 0.001). There was also a significant difference in the amplitude of pSTR between the two groups starting from 6 months (p < 0.001). Furthermore, a significant difference in the inner retinal thickness, betwe...

Gerace, D, Martiniello-Wilks, R, Habib, R & Simpson, AM 2019, 'Luciferase-based reporting of suicide gene activity in murine mesenchymal stem cells', PLOS ONE, vol. 14, no. 7, pp. e0220013-e0220013.
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© 2019 Gerace et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Due to their ease of isolation, gene modification and tumor-homing properties, mesenchymal stem cells (MSCs) are an attractive cellular vehicle for the delivery of toxic suicide genes to a variety of cancers in pre-clinical models. In addition, the incorporation of suicide genes in stem cell-derived cell replacement therapies improves their safety profile by permitting graft destruction in the event of unexpected tumorigeneses or unwanted differentiation. Due to the functional requirement of ATP for the Firefly luciferase gene Luc2 to produce light, luciferase-based reporting of cytotoxicity can be engineered into potential cell therapies. Consequently, we nucleofected mammalian expression plasmids containing both the Luc2 and the yeast fusion cytosine deaminase uracil phosphoribosyltransferase (CDUPRT) genes for expression in murine MSCs to assess luciferase as a reporter of suicide gene cytotoxicity, and MSC as vehicles of suicide gene therapy. In vitro bioluminescence imaging (BLI) showed that following the addition of the non-toxic prodrug fluorocytosine (5-FC), CDUPRT-expressing MSCs displayed enhanced cytotoxicity in comparison to Luc2 reporter MSC controls. This study demonstrates the utility of luciferase as a reporter of CDUPRT-mediated cytotoxicity in murine MSC using BLI.

Gerace, D, Martiniello-Wilks, R, Habib, R, Ren, B, Nassif, NT, O’Brien, BA & Simpson, AM 2019, 'Ex Vivo Expansion of Murine MSC Impairs Transcription Factor-Induced Differentiation into Pancreatic β-Cells', Stem Cells International, vol. 2019, pp. 1-15.
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Combinatorial gene and cell therapy as a means of generating surrogate β-cells has been investigated for the treatment of type 1 diabetes (T1D) for a number of years with varying success. One of the limitations of current cell therapies for T1D is the inability to generate sufficient quantities of functional transplantable insulin-producing cells. Due to their impressive immunomodulatory properties, in addition to their ease of expansion and genetic modification ex vivo, mesenchymal stem cells (MSCs) are an attractive alternative source of adult stem cells for regenerative medicine. To overcome the aforementioned limitation of current therapies, we assessed the utility of ex vivo expanded bone marrow-derived murine MSCs for their persistence in immune-competent and immune-deficient animal models and their ability to differentiate into surrogate β-cells. CD45-/Ly6+ murine MSCs were isolated from the bone marrow of nonobese diabetic (NOD) mice and nucleofected to express the bioluminescent protein, Firefly luciferase (Luc2). The persistence of a subcutaneous (s.c.) transplant of Luc2-expressing MSCs was assessed in immune-competent (NOD) (n=4) and immune-deficient (NOD/Scid) (n=4) animal models of diabetes. Luc2-expressing MSCs persisted for 2 and 12 weeks, respectively, in NOD and NOD/Scid mice. Ex vivo expanded MSCs were transduced with the HMD lentiviral vector (MOI = 10) to express furin-...

Gerami, A, Alzahid, Y, Mostaghimi, P, Kashaninejad, N, Kazemifar, F, Amirian, T, Mosavat, N, Ebrahimi Warkiani, M & Armstrong, RT 2019, 'Microfluidics for Porous Systems: Fabrication, Microscopy and Applications', Transport in Porous Media, vol. 130, no. 1, pp. 277-304.
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© 2018, Springer Nature B.V. No matter how sophisticated the structures are and on what length scale the pore sizes are, fluid displacement in porous media can be visualized, captured, mimicked and optimized using microfluidics. Visualizing transport processes is fundamental to our understanding of complex hydrogeological systems, petroleum production, medical science applications and other engineering applications. Microfluidics is an ideal tool for visual observation of flow at high temporal and spatial resolution. Experiments are typically fast, as sample volume is substantially low with the use of miniaturized devices. This review first discusses the fabrication techniques for generating microfluidics devices, experimental setups and new advances in microfluidic fabrication using three-dimensional printing, geomaterials and biomaterials. We then address multiphase transport in subsurface porous media, with an emphasis on hydrology and petroleum engineering applications in the past few decades. We also cover the application of microfluidics to study membrane systems in biomedical science and particle sorting. Lastly, we explore how synergies across different disciplines can lead to innovations in this field. A number of problems that have been resolved, topics that are under investigation and cutting-edge applications that are emerging are highlighted.

Ghaffari Jadidi, M, Valls Miro, J & Dissanayake, G 2019, 'Sampling-based incremental information gathering with applications to robotic exploration and environmental monitoring', The International Journal of Robotics Research, vol. 38, no. 6, pp. 658-685.
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We propose a sampling-based motion-planning algorithm equipped with an information-theoretic convergence criterion for incremental informative motion planning. The proposed approach allows dense map representations and incorporates the full state uncertainty into the planning process. The problem is formulated as a constrained maximization problem. Our approach is built on rapidly exploring information-gathering algorithms and benefits from the advantages of sampling-based optimal motion-planning algorithms. We propose two information functions and their variants for fast and online computations. We prove an information-theoretic convergence for an entire exploration and information-gathering mission based on the least upper bound of the average map entropy. A natural automatic stopping criterion for information-driven motion control results from the convergence analysis. We demonstrate the performance of the proposed algorithms using three scenarios: comparison of the proposed information functions and sensor configuration selection, robotic exploration in unknown environments, and a wireless signal strength monitoring task in a lake from a publicly available dataset collected using an autonomous surface vehicle.

Ghorbani, F, Abbaszadeh, H, Mehdizadeh, A, Ebrahimi-Warkiani, M, Rashidi, M-R & Yousefi, M 2019, 'Biosensors and nanobiosensors for rapid detection of autoimmune diseases: a review', Microchimica Acta, vol. 186, no. 12.
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© 2019, Springer-Verlag GmbH Austria, part of Springer Nature. This review (with 77 refs.) describes the progress that has been made in biosensors for the detection of autoimmune diseases, mainly via detection of autoantibodies. In addition, specific proteins, cytokines and ions have also been introduced as promising diagnostic biomarkers. Following an introduction into the various kinds of autoimmune diseases, we first discuss the state of the art in respective electrochemical biosensors and nanobiosensors (with subsections on amperometric, impedimetric, voltammetric and photoelectrochemical methods). The next large chapter covers optical methods (with subsections on electrochemiluminescence, fluorescence and surface plasmon resonance). We then make a critical comparison between commercially available kits used for detection of autoimmune diseases with the established biosensors. Several Tables are also presented that give an overview on the wealth of methods and nanomaterials. Finally, in the conclusion part, we summarize the current status, addresse present issues, and give an outlook on potential future opportunities. [Figure not available: see fulltext.].

Ghorbani, S, Eyni, H, Khosrowpour, Z, Salari Asl, L, Shabani, R, Nazari, H, Mehdizadeh, M, Ebrahimi Warkiani, M & Amjadi, F 2019, 'Spermatogenesis induction of spermatogonial stem cells using nanofibrous poly(l‐lactic acid)/multi‐walled carbon nanotube scaffolds and naringenin', Polymers for Advanced Technologies, vol. 30, no. 12, pp. 3011-3025.
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Spermatogenesis is a process in which animals generate spermatozoa from spermatogonial stem cells (SSCs). Successful in vitro differentiation of SSCs towards spermatids holds a significant promise for regeneration of impaired spermatogenesis. The present study aims to evaluate the efficiency of a 3D culture containing naringenin on proliferation and differentiation potentials of mouse SSCs. In this study, multi‐walled carbon nanotubes (MWCNTs) were incorporated into poly(l‐lactic acid) (PLLA) fibers via electrospinning technique. The fibrous PLLA/MWCNTs were studied by Fourier‐transform infrared spectroscopy (FTIR), transmission electron microscope (TEM), water contact angle measurements, electrical conductivity, and mechanical properties. Next, the SSCs were seeded into the PLLA/MWCNTs scaffolds and exhibited preferable survival and differentiation efficiency to subsequent cell lines. To shed more light on this matter, the immunocytochemistry, reverse‐transcription polymerase chain reaction (RT‐PCR), and qRT‐PCR results showed that the aforementioned cells on the 3D fabrics overexpressed the C‐kit and SYCP3 proteins. In addition, the reactive oxygen species (ROS) measurement data demonstrated that naringenin, an effective antioxidant, plays an important role in in vitro spermatogenesis. Taken together, the results of this study revealed the synergistic effects of 3D scaffolds and naringenin for efficient spermatogenesis in laboratories.

Giannopoulos, S, Samardzic, K, Raymond, BBA, Djordjevic, SP & Rodgers, KJ 2019, 'L-DOPA causes mitochondrial dysfunction in vitro: A novel mechanism of L-DOPA toxicity uncovered', The International Journal of Biochemistry & Cell Biology, vol. 117, pp. 105624-105624.
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In Parkinson's disease (PD), as in many other neurodegenerative disorders, mitochondrial dysfunction, protein misfolding, and proteotoxic stress underly the disease process. For decades, the primary symptomatic treatment for PD has been the dopamine precursor L-DOPA (Levodopa). L-DOPA however can initiate protein misfolding through its ability to mimic the protein amino acid L-tyrosine, resulting in random errors in aminoacylation and L-DOPA becoming mistakenly inserted into the polypeptide chain of proteins in place of L-tyrosine. In the present study we examined the impact that the generation of DOPA-containing proteins had on human neuroblastoma cell (SH-SY5Y) function in vitro. We showed that even in the presence of antioxidants there was a significant accumulation of cytosolic ubiquitin in DOPA-treated cells, an upregulation in the endosomal-lysosomal degradation system, deleterious changes to mitochondrial morphology and a marked decline in mitochondrial function.The effects of L-DOPA on mitochondrial function were not observed with D-DOPA, the stereoisomer of L-DOPA that cannot be inserted into proteins so did not result from oxidative stress. We could fully protect against these effects by co-treatment with L-tyrosine, supporting the view that misincorporation of L-DOPA into proteins contributed to these cytotoxic effects, leading us to suggest that co-treatment with L-tyrosine could be beneficial therapeutically.

Gill, AJ, Lim, G, Cheung, VKY, Andrici, J, Perry-Keene, JL, Paik, J, Sioson, L, Clarkson, A, Sheen, A, Luxford, C, Elston, MS, Meyer-Rochow, GY, Nano, MT, Kruijff, S, Engelsman, AF, Sywak, M, Sidhu, SB, Delbridge, LW, Robinson, BG, Marsh, DJ, Toon, CW, Chou, A & Clifton-Bligh, RJ 2019, 'Parafibromin-deficient (HPT-JT Type, CDC73 Mutated) Parathyroid Tumors Demonstrate Distinctive Morphologic Features', American Journal of Surgical Pathology, vol. 43, no. 1, pp. 35-46.
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The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cyt...

Gracia, L, Solanes, JE, Muñoz-Benavent, P, Miro, JV, Perez-Vidal, C & Tornero, J 2019, 'Human-robot collaboration for surface treatment tasks', Interaction Studies, vol. 20, no. 1, pp. 148-184.
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Abstract This paper presents a human-robot closely collaborative solution to cooperatively perform surface treatment tasks such as polishing, grinding, finishing, deburring, etc. The proposed scheme is based on task priority and non-conventional sliding mode control. Furthermore, the proposal includes two force sensors attached to the manipulator end-effector and tool: one sensor is used to properly accomplish the surface treatment task, while the second one is used by the operator to guide the robot tool. The applicability and feasibility of the proposed collaborative solution for robotic surface treatment are substantiated by experimental results using a redundant 7R manipulator: the Sawyer collaborative robot.

Grandou, C, Wallace, L, Allen, N, Impellizzeri, F & Coutts, A 2019, 'Overtraining in Resistance Exercise: A Systematic Review and Methodological Appraisal of the Literature', Journal of Science and Medicine in Sport, vol. 22, pp. S85-S85.
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Guo, K, Chai, R, Candra, H, Guo, Y, Song, R, Nguyen, H & Su, S 2019, 'A Hybrid Fuzzy Cognitive Map/Support Vector Machine Approach for EEG-Based Emotion Classification Using Compressed Sensing', International Journal of Fuzzy Systems, vol. 21, no. 1, pp. 263-273.
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© 2018, Taiwan Fuzzy Systems Association and Springer-Verlag GmbH Germany, part of Springer Nature. Due to the high dimensional, non-stationary and non-linear properties of electroencephalogram (EEG), a significant portion of research on EEG analysis remains unknown. In this paper, a novel approach to EEG-based human emotion study is presented using Big Data methods with a hybrid classifier. An EEG dataset is firstly compressed using compressed sensing, then, wavelet transform features are extracted, and a hybrid Support Vector Machine (SVM) and Fuzzy Cognitive Map classifier is designed. The compressed data is only one-fourth of the original size, and the hybrid classifier has the average accuracy by 73.32%. Comparing to a single SVM classifier, the average accuracy is improved by 3.23%. These outcomes show that psychological signal can be compressed without the sparsity identity. The stable and high accuracy classification system demonstrates that EEG signal can detect human emotion, and the findings further prove the existence of the inter-relationship between various regions of the brain.

Guo, Q, Zhang, Y, Celler, BG & Su, SW 2019, 'Neural Adaptive Backstepping Control of a Robotic Manipulator With Prescribed Performance Constraint', IEEE Transactions on Neural Networks and Learning Systems, vol. 30, no. 12, pp. 3572-3583.
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IEEE This paper presents an adaptive neural network (NN) control of a two-degree-of-freedom manipulator driven by an electrohydraulic actuator. To restrict the system output in a prescribed performance constraint, a weighted performance function is designed to guarantee the dynamic and steady tracking errors of joint angle in a required accuracy. Then, a radial-basis-function NN is constructed to train the unknown model dynamics of a manipulator by traditional backstepping control (TBC) and obtain the preliminary estimated model, which can replace the preknown dynamics in the backstepping iteration. Furthermore, an adaptive estimation law is adopted to self-tune every trained-node weight, and the estimated model is online optimized to enhance the robustness of the NN controller. The effectiveness of the proposed control is verified by comparative simulation and experimental results with Proportional-integral-derivative and TBC methods.

Guo, Z, Yang, C, Maritz, MF, Wu, H, Wilson, P, Warkiani, ME, Chien, C, Kempson, I, Aref, AR & Thierry, B 2019, 'Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature', Advanced Materials Technologies, vol. 4, no. 4, pp. 1800726-1800726.
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AbstractThe therapeutic ratio of radiotherapy is limited by acute or chronic side effects with often severe consequences to patients. The microvasculature is a central player involved in both tumor responses and healthy tissue/organ radiological injuries. However, current preclinical vascular models based on 2D culture offer only limited radiobiological insight due to their failure in recapitulating the 3D nature experienced by endothelial cells within the human microvasculature. To address this issue, the use of a 3D microvasculature‐on‐a‐chip microfluidic technology is demonstrated in radiobiological studies. Within this vasculogenesis model a perfusable network that structurally mimics the human microvasculature is formed and the biological response to ionizing radiation including cellular apoptosis, vessel tight adherens junction breakage, DNA double strand break, and repair is systematically investigated. In comparison to cells grown in a 2D environment, human umbilical vein endothelial cells in the 3D microvasculature‐on‐a‐chip displays significant differences in biological responses, especially at high X‐ray dose. This data confirms the feasibility of using microvascular‐on‐a‐chip models for radiobiological studies. Such vasculogenesis models have strong potential to yield more accurate prediction of healthy tissue responses to ionizing radiation as well as to guide the development of risk‐reducing strategies to prevent radiation‐induced acute and long‐term side‐effects.

Hadzhiev, Y, Qureshi, HK, Wheatley, L, Cooper, L, Jasiulewicz, A, Van Nguyen, H, Wragg, JW, Poovathumkadavil, D, Conic, S, Bajan, S, Sik, A, Hutvàgner, G, Tora, L, Gambus, A, Fossey, JS & Müller, F 2019, 'A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation', Nature Communications, vol. 10, no. 1.
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AbstractMost metazoan embryos commence development with rapid, transcriptionally silent cell divisions, with genome activation delayed until the mid-blastula transition (MBT). However, a set of genes escapes global repression and gets activated before MBT. Here we describe the formation and the spatio-temporal dynamics of a pair of distinct transcription compartments, which encompasses the earliest gene expression in zebrafish. 4D imaging of pri-miR430and zinc-finger-gene activities by a novel, native transcription imaging approach reveals transcriptional sharing of nuclear compartments, which are regulated by homologous chromosome organisation. These compartments carry the majority of nascent-RNAs and active Polymerase II, are chromatin-depleted and represent the main sites of detectable transcription before MBT. Transcription occurs during the S-phase of increasingly permissive cleavage cycles. It is proposed, that the transcription compartment is part of the regulatory architecture of embryonic nuclei and offers a transcriptionally competent environment to facilitate early escape from repression before global genome activation.

Halson, SL, Hahn, AG & Coutts, AJ 2019, 'Combining Research With “Servicing” to Enhance Sport Performance', International Journal of Sports Physiology and Performance, vol. 14, no. 5, pp. 549-550.
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Hamedi-Shahraki, S, Eshraghian, M-R, Yekaninejad, M-S, Nikoobakht, M, Rasekhi, A, Chen, H & Pakpour, A 2019, 'Health-related quality of life and medication adherence in elderly patients with epilepsy', Neurologia i Neurochirurgia Polska, vol. 53, no. 2, pp. 123-130.
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OBJECTIVE:Considering the high prevalence of epilepsy in the elderly and the importance of maximising their quality of life (QoL), this study aimed to investigate the relationship between medication adherence and QoL, and the mediating effects of medication adherence on the association between serum antiepileptic drug (AED) level and seizure severity with QoL in elderly epileptics. METHODS:In a longitudinal study, 766 elderly patients with epilepsy who were prescribed a minimum of one antiepileptic drug were selected by convenience sampling method. A Medication Adherence Report Scale (MARS-5) questionnaire was completed at the baseline. Seizure severity and QoL were assessed after six months using the Liverpool Seizure Severity Scale (LSSS) and the QoL in Epilepsy (QOLIE-31) questionnaires respectively. Serum level of AED was also measured at six-month follow-up. RESULTS:Medication adherence was significantly correlated with both seizure severity (β = -0.33, p < 0.0001) and serum AED level (β = 0.29, p < 0.0001) after adjusting for demographic and clinical characteristics. Neither QoL nor its sub-classes were correlated with seizure severity. In addition, a significant correlation was not observed between serum AED level and QoL. However, medication adherence was significantly correlated with QoL (β = 0.30, p < 0.0001). The mediating effects of medication adherence on the association between serum AED level (Z = 3.39, p < 0.001) and seizure severity (Z = -3.47, p < 0.001) with QoL were supported by the Sobel test. CONCLUSION:This study demonstrates that medication adherence has a beneficial impact on QoL in elderly epileptics. Therefore, adherence to treatment should be monitored to improve their QoL.

Hayati, H, Mahdavi, F & Eager, D 2019, 'Analysis of Agile Canine Gait Characteristics Using Accelerometry', Sensors, vol. 19, no. 20, pp. 4379-4379.
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The high rate of severe injuries associated with racing greyhounds poses a significant problem for both animal welfare and the racing industry. Using accelerometry to develop a better understanding of the complex gait of these agile canines may help to eliminate injury contributing factors. This study used a single Inertial Measurement Unit (IMU) equipped with a tri-axial accelerometer to characterise the galloping of thirty-one greyhounds on five different race tracks. The dorsal-ventral and anterior-posterior accelerations were analysed in both the time and frequency domains. The fast Fourier transform (FFT) and Morlet wavelet transform were applied to signals. The time-domain signals were synced with the corresponding high frame rate videos of the race. It was observed that the acceleration peaks in the dorsal-ventral accelerations correspond to the hind-leg strikes which were noted to be fifteen times the greyhound’s weight. The FFT analysis showed that the stride frequencies in all tracks were around 3.5 Hz. The Morlet wavelet analysis also showed a reduction in both the frequency and magnitude of signals, which suggests a speed reduction throughout the race. Also, by detecting abrupt changes along the track, the wavelet analysis highlighted potentially hazardous locations on the track. In conclusion, the methods applied in this research contribute to animal safety and welfare by eliminating the factors leading to injuries through optimising the track design and surface type.

He, P, Smith, A, Gelissen, IC & Ammit, AJ 2019, 'The effect of statins and the synthetic LXR agonist T0901317 on expression of ABCA1 transporter protein in human lung epithelial cell lines in vitro', Pharmacological Reports, vol. 71, no. 6, pp. 1219-1226.
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BACKGROUND: The pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with dyslipidemia, an established co-morbidity. Statins treat hypercholesterolemia, but more recently have been trailed in the setting of COPD for their potential anti-inflammatory benefits. The outcomes of prospective trials however have been inconsistent. Thus, we hypothesize that the variation in results may have been due to statin-induced downregulation of ATP-binding cassette transporter A1 (ABCA1), thereby reducing cholesterol export. This study aims to elucidate whether statin treatment in a cellular model of COPD leads to a decrease in ABCA1 protein expression. METHODS: To mimic the inflammatory environment of COPD, two commonly used lung epithelial cell lines (BEAS-2B and A549) were treated with tumor necrosis factor (TNF), and co-treated with cholesterol/25-hydroxycholesterol (25-OH) to mimic dyslipidemia. ABCA1 protein was detected by Western Blotting. RESULTS: We unexpectedly showed that statins did not affect ABCA1 expression. However, the LXR agonist T0901317 significantly increased ABCA1 expression in both cell lines, while TNF, cholesterol or 25-OH induced ABCA1 protein upregulation in BEAS-2B cells, indicating cell line differences in response. There was also evidence of synergistic impacts of combined treatments on ABCA1 upregulation in BEAS-2B cells. CONCLUSION: Statins did not have an impact on ABCA1 expression in lung epithelial cell lines, disproving our original hypothesis. However, we showed for the first time, the effect of the inflammatory cytokine TNF, cholesterol/25-OH, statins and the LXR agonist T0901317 on expression of ABCA1 transporter protein in human lung epithelial cell lines in vitro. We hope that these in vitro studies may prove beneficial for addressing dyslipidemia in COPD in the future.

Henderson, MJ, Fransen, J, McGrath, JJ, Harries, SK, Poulos, N & Coutts, AJ 2019, 'Individual Factors Affecting Rugby Sevens Match Performance', International Journal of Sports Physiology and Performance, vol. 14, no. 5, pp. 620-626.
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Purpose: To examine the collective independent influence of a range of individual characteristics on physical and technical match performance during international rugby sevens matches. Methods: Data were collected from 20 international rugby sevens players from 1 team across 1 season. Activity profiles were measured using wearable microtechnology devices, and technical performance measures were collected from match video analysis. Subjective well-being measures were collected using a well-being questionnaire completed on the morning of main training days, and groin-squeeze assessments at 0° and 60° knee flexion were also conducted using a sphygmomanometer. Assessments of aerobic fitness were completed periodically across the season, including time to complete a 2-km run and final velocity during the 30:15 Intermittent Fitness Test (VIFT). A principal-components analysis was conducted to reduce the dimensionality of the physical and technical variables into single-factor values. Linear mixed models were then constructed to examine the collective influence of a range of individual contextual variables on physical and technical performance factors. Results: Increased muscle soreness, stress, and VIFT were associated with trivial to small increases in physical and technical performance values, whereas trivial to small decreases were associated with higher perceived recovery, body weight, and groin squeeze (0° knee flexion). Conclusions: A range of well-being metrics are required to account for a significant portion of the variance in physical and technical performance. These factors may be manipulated by coaches or practitioners to achieve favorable physiological readiness that may lea...

Henderson, MJ, Fransen, J, McGrath, JJ, Harries, SK, Poulos, N & Coutts, AJ 2019, 'Situational factors affecting rugby sevens match performance', Science and Medicine in Football, vol. 3, no. 4, pp. 275-280.
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© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Purpose: To examine the independent influence of a range of situational factors on physical and technical match performance during international rugby sevens matches. Methods: Data was collected from 20 professional rugby sevens players from one team across one competitive season. Activity profiles were measured using wearable microtechnology devices, and technical performance measures were collected using match video analysis. A principal components analysis was conducted to reduce the dimensionality of the physical and technical match performance variables into single index values incorporating each variable’s distinct information. Linear mixed models were then constructed to examine the collective influence of external contextual factors on physical and technical index scores. Results: Increased points conceded, a winning match outcome, and more favourable weather all had positive impacts on the Physical Performance Factor, with all other situational factors examined not contributing to a significantly better model fit. Technical Performance Factor values were shown to increase with longer match involvement durations and decrease when playing against higher ranked opponents. Conclusions: These findings show that winning the match, conceding more points, and more favourable weather conditions are associated with increased physical performance; whilst technical performance improved with longer playing durations and playing lower ranked opponents.

Heneka, N, Bhattarai, P, Shaw, T, Rowett, D, Lapkin, S & Phillips, JL 2019, 'Clinicians’ perceptions of opioid error–contributing factors in inpatient palliative care services: A qualitative study', Palliative Medicine, vol. 33, no. 4, pp. 430-444.
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Background: Opioid errors are a leading cause of patient harm and adversely impact palliative care inpatients’ pain and symptom management. Yet, the factors contributing to opioid errors in palliative care are poorly understood. Identifying and better understanding the individual and system factors contributing to these errors is required to inform targeted strategies. Objectives: To explore palliative care clinicians’ perceptions of the factors contributing to opioid errors in Australian inpatient palliative care services. Design: A qualitative study using focus groups or semi-structured interviews. Settings: Three specialist palliative care inpatient services in New South Wales, Australia. Participants: Inpatient palliative care clinicians who are involved with, and/or have oversight of, the services’ opioid delivery or quality and safety processes. Methods: Deductive thematic content analysis of the qualitative data. The Yorkshire Contributory Factors Framework was applied to identify error-contributing factors. Findings: A total of 58 clinicians participated in eight focus groups and 20 semi-structured interviews. Nine key error contributory factor domains were identified, including: active failures; task characteristics of opioid preparation; clinician inexperience; sub-optimal skill mix; gaps in support from central functions; the drug preparation environment; and sub-optimal clinical communication. Conclusion: This study identified multiple system-level factors contributi...

Hesamian, MH, Jia, W, He, X & Kennedy, P 2019, 'Deep Learning Techniques for Medical Image Segmentation: Achievements and Challenges', Journal of Digital Imaging, vol. 32, no. 4, pp. 582-596.
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© 2019, The Author(s). Deep learning-based image segmentation is by now firmly established as a robust tool in image segmentation. It has been widely used to separate homogeneous areas as the first and critical component of diagnosis and treatment pipeline. In this article, we present a critical appraisal of popular methods that have employed deep-learning techniques for medical image segmentation. Moreover, we summarize the most common challenges incurred and suggest possible solutions.

Ho-Pham, LT & Nguyen, TV 2019, 'Association between trabecular bone score and type 2 diabetes: a quantitative update of evidence', Osteoporosis International, vol. 30, no. 10, pp. 2079-2085.
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© 2019, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: Patients with type 2 diabetes have an increased risk of fracture despite having a higher areal bone mineral density. This meta-analysis showed that compared with controls, diabetic patients had a lower trabecular bone score (TBS) than non-diabetic individuals, suggesting that TBS can be a useful measurement for the assessment of fracture risk in diabetic patients. Introduction: The association between type 2 diabetes and trabecular bone score (TBS) has not been clear. The present study sought to answer the specific question of whether patients with type 2 diabetes have a lower TBS than those without diabetes. Methods: Using electronic and manual search, we identified 12 studies that had examined the association between type 2 diabetes and TBS between 2013 and 2019. These studies involved 35,546 women and 4962 men aged 30 years and older. We extracted the mean and standard deviation of TBS for patients with and without diabetes. The synthesis of effect sizes was done by the random effects meta-analysis model. Results: Patients with diabetes had significantly lower TBS than those without diabetes, with standardized mean difference being − 0.31 (95% CI, − 0.45 to − 0.16). The difference was greater in women (− 0.50; 95% CI, − 0.69 to − 0.32) than in men (− 0.04; 95% CI, − 0.17 to 0.10). Compared with normal individuals, those with prediabetes had significantly lower TBS (d = − 0.13; 95% CI, − 0.23 to − 0.04; P = 0.005). There was heterogeneity between the studies, with the index of inconsistency (I2) ranging from 92% (in women) to 69.5% (in men). Conclusion: Patients with type 2 diabetes have a lower TBS than non-diabetic individuals, suggesting that TBS can be a useful measurement for the assessment of fracture risk in diabetic patients.

Ho-Pham, LT, Tran, B, Do, AT & Nguyen, TV 2019, 'Association between pre-diabetes, type 2 diabetes and trabecular bone score: The Vietnam Osteoporosis Study', Diabetes Research and Clinical Practice, vol. 155, pp. 107790-107790.
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© 2019 Aims: Trabecular bone score (TBS) is a surrogate indicator of bone microarchitecture. The present study sought to examine the association between type 2 diabetes (T2D) and trabecular bone score (TBS) in adult Vietnamese men and women. Methods: The study was part of the Vietnam Osteoporosis Study, in which 2702 women and 1398 men aged ≥30 years were recruited from the general community in Ho Chi Minh City. HbA1c levels were measured by the ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan), and classified into 3 groups: normal if HbA1c < 5.7%; pre-diabetes (5.7–6.4%); and diabetes (>6.4%). TBS was evaluated by iNsight Software, version 2.1 (Medimaps, Merignac, France) on lumbar spine BMD scan (Hologic Horizon). Differences in TBS between diabetic status were analyzed by the multivariable regression model with adjustment for age and body mass index. Results: The prevalence of pre-diabetes and diabetes in men and women was 30.2% and 8.3%, respectively. In women, TBS was lower in pre-diabetes (−0.02; P < 0.001) and diabetes (−0.02; P < 0.001) compared with normal individuals. In men, there was no statistically significant difference in TBS between diabetic status. Moreover, TBS was significantly inversely correlated with HbA1c levels in women (P = 0.01), but not in men (P = 0.89). Conclusion: Women, but not men, with type 2 diabetes and pre-diabetes have lower TBS than individuals without diabetes. These data suggest that diabetes and prediabetes are associated with deterioration of bone microarchitecture.

Hoppstädter, J & Ammit, AJ 2019, 'Role of Dual-Specificity Phosphatase 1 in Glucocorticoid-Driven Anti-inflammatory Responses', Frontiers in Immunology, vol. 10, no. JUN, p. 1446.
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Copyright © 2019 Hoppstädter and Ammit. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Glucocorticoids (GCs) potently inhibit pro-inflammatory responses and are widely used for the treatment of inflammatory diseases, such as allergies, autoimmune disorders, and asthma. Dual-specificity phosphatase 1 (DUSP1), also known as mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), exerts its effects by dephosphorylation of MAPKs, i.e., extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Endogenous DUSP1 expression is tightly regulated at multiple levels, involving both transcriptional and post-transcriptional mechanisms. DUSP1 has emerged as a central mediator in the resolution of inflammation, and upregulation of DUSP1 by GCs has been suggested to be a key mechanism of GC actions. In this review, we discuss the impact of DUSP1 on the efficacy of GC-mediated suppression of inflammation and address the underlying mechanisms.

Hosie, A, Phillips, J, Lam, L, Kochovska, S, Noble, B, Brassil, M, Kurrle, SE, Cumming, A, Caplan, GA, Chye, R, Le, B, Ely, EW, Lawlor, PG, Bush, SH, Davis, JM, Lovell, M, Brown, L, Fazekas, B, Cheah, SL, Edwards, L & Agar, M 2019, 'Multicomponent non-pharmacological intervention to prevent delirium for hospitalised people with advanced cancer: study protocol for a phase II cluster randomised controlled trial', BMJ Open, vol. 9, no. 1, pp. e026177-e026177.
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IntroductionDelirium is a significant medical complication for hospitalised patients. Up to one-third of delirium episodes are preventable in older inpatients through non-pharmacological strategies that support essential human needs, such as physical and cognitive activity, sleep, hydration, vision and hearing. We hypothesised that a multicomponent intervention similarly may decrease delirium incidence, and/or its duration and severity, in inpatients with advanced cancer. Prior to a phase III trial, we aimed to determine if a multicomponent non-pharmacological delirium prevention intervention is feasible and acceptable for this specific inpatient group.Methods and analysisThe study is a phase II cluster randomised wait-listed controlled trial involving inpatients with advanced cancer at four Australian palliative care inpatient units. Intervention sites will introduce delirium screening, diagnostic assessment and a multicomponent delirium prevention intervention with six domains of care: preserving natural sleep; maintaining optimal vision and hearing; optimising hydration; promoting communication, orientation and cognition; optimising mobility; and promoting family partnership. Interdisciplinary teams will tailor intervention delivery to each site and to patient need. Control sites will first introduce only delirium screening and diagnosis, later implementing the intervention, modified according to initial results. The primary outcome is adherence to the intervention during the first seven days of admission, measured for 40 consecutively admitted eligible patients. Secondary outcomes relate to fidelity and feasibility, acceptability and sustainability of the study intervention, processes and measures in this patient population, using quantitative and qualitative measures. Delirium incidence and severity will be measured to inform power calculations...

Hosie, A, Siddiqi, N, Featherstone, I, Johnson, M, Lawlor, PG, Bush, SH, Amgarth-Duff, I, Edwards, L, Cheah, SL, Phillips, J & Agar, M 2019, 'Inclusion, characteristics and outcomes of people requiring palliative care in studies of non-pharmacological interventions for delirium: A systematic review', Palliative Medicine, vol. 33, no. 8, pp. 878-899.
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Background: Delirium is common, distressing, serious and under-researched in specialist palliative care settings. Objectives: To examine whether people requiring palliative care were included in non-pharmacological delirium intervention studies in inpatient settings, how they were characterised and what their outcomes were. Design: Systematic review (PROSPERO 2017 CRD42017062178). Data sources: Systematic search in March 2017 for non-pharmacological delirium intervention studies in adult inpatients. Database search terms were ‘delirium’, ‘hospitalisation’, ‘inpatient’, ‘palliative care’, ‘hospice’, ‘critical care’ and ‘geriatrics’. Scottish Intercollegiate Guidelines Network methodological checklists guided risk of bias assessment. Results: The 29 included studies were conducted between 1994 and 2015 in diverse settings in 15 countries (9136 participants, mean age = 76.5 years ( SD = 8.1), 56% women). Most studies tested multicomponent interventions ( n = 26) to prevent delirium ( n = 19). Three-quarters of the 29 included studies ( n = 22) excluded various groups of people requiring palliative care; however, inclusion criteria, participant diagnoses, illness severity and mortality indicated their presence in almost all studies ( n = 26). Of these, 21 studies did not characterise participants requiring palliative care or report their specific outcomes (72%), four reported outcomes for older people with frailty, dementia, cancer and comorbidities, and one was explicitly focused on people receiving palliative care. Study heterogeneity and limitations precluded definitive determination of intervention effectiveness and only allowed interpretations of feasibility for ...

Hossain, KR, Turkewitz, DR, Holt, SA, Herson, L, Brown, LJ, Cornell, BA, Curmi, PMG & Valenzuela, SM 2019, 'A conserved GXXXG motif in the transmembrane domain of CLIC proteins is essential for their cholesterol-dependant membrane interaction', Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1863, no. 8, pp. 1243-1253.
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© 2019 Elsevier B.V. Background: Sterols have been reported to modulate conformation and hence the function of several membrane proteins. One such group is the Chloride Intracellular Ion Channel (CLIC)family of proteins. The CLIC protein family consists of six evolutionarily conserved protein members in vertebrates. These proteins exist as both monomeric soluble proteins and as membrane bound proteins. To date, the structure of their membrane-bound form remains unknown. In addition to several studies indicating cellular redox environment and pH as facilitators of CLIC1 insertion into membranes, we have also demonstrated that the spontaneous membrane insertion of CLIC1 is regulated by membrane cholesterol. Method: We have performed Langmuir-film, Impedance Spectroscopy and Molecular Docking Simulations to study the role of this GXXXG motif in CLIC1 interaction with cholesterol. Results: Unlike CLIC1-wild-type protein, the G18A and G22A mutants, that form part of the GXXXG motif, showed much slower initial kinetics and lower ion channel activity compared to the native protein. This difference can be attributed to the significantly reduced membrane interaction and insertion rate of the mutant proteins and/or slower formation of the final membrane configuration of the mutant proteins once in the membrane. Conclusion: In this study, our findings uncover the identification of a GXXXG motif in CLIC1, which likely serves as the cholesterol-binding domain, that facilitates the protein's membrane interaction and insertion. Furthermore, we were able to postulate a model by which CLIC1 can autonomously insert into membranes to form functional ion channels. General significance: Members of the CLIC family of proteins demonstrate unusual structural and dual functional properties – as ion channels and enzymes. Elucidating how the CLIC proteins' interact with membranes, thus allowing them to switch between their soluble and membrane form, will provide key information a...

Hu, X, Zheng, W, Zhu, Q, Gu, L, Du, Y, Han, Z, Zhang, X, Carter, DR, Cheung, BB, Qiu, A & Jiang, C 2019, 'Increase in DNA Damage by MYCN Knockdown Through Regulating Nucleosome Organization and Chromatin State in Neuroblastoma', Frontiers in Genetics, vol. 10, no. JUL.
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© 2019 Hu, Zheng, Zhu, Gu, Du, Han, Zhang, Carter, Cheung, Qiu and Jiang. As a transcription factor, MYCN regulates myriad target genes including the histone chaperone FACT. Moreover, FACT and MYCN expression form a forward feedback loop in neuroblastoma. It is unclear whether MYCN is involved in chromatin remodeling in neuroblastoma through regulation of its target genes. We showed here that MYCN knockdown resulted in loss of the nucleosome-free regions through nucleosome assembly in the promoters of genes functionally enriched for DNA repair. The active mark H3K9ac was removed or replaced by the repressive mark H3K27me3 in the promoters of double-strand break repair-related genes upon MYCN knockdown. Such chromatin state alterations occurred only in MYCN-bound promoters. Consistently, MYCN knockdown resulted in a marked increase in DNA damage in the treatment with hydroxyurea. In contrast, nucleosome reorganization and histone modification changes in the enhancers largely included target genes with tumorigenesis-related functions such as cell proliferation, cell migration, and cell-cell adhesion. The chromatin state significantly changed in both MYCN-bound and MYCN-unbound enhancers upon MYCN knockdown. Furthermore, MYCN knockdown independently regulated chromatin remodeling in the promoters and the enhancers. These findings reveal the novel epigenetic regulatory role of MYCN in chromatin remodeling and provide an alternative potential epigenetic strategy for MYCN-driven neuroblastoma treatment.

Huston, WM, Cranfield, CG, Forbes, SL & Leigh, A 2019, 'A sponsorship action plan for increasing diversity in STEMM', Ecology and Evolution, vol. 9, no. 5, pp. 2340-2345.
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AbstractThere are numerous structural and cultural barriers to the progression of women and marginalized groups to leadership in academia, especially in Science, Technology, Engineering, Mathematics and Medicine (STEMM). A range of interventions have been described to address this inequity, with varying success. Here, we suggest that sponsorship could be one effective intervention and propose an institutional action plan to implement a sponsorship program in academia. We outline why sponsorship could be an effective strategy, especially if implemented through a deliberate program by an institution. We then detail the three components of an action plan to be considered in implementation: the elements of the program, the activities that sponsorship in academia likely encompasses, and the selection of sponsors and protégés. The plan could also be enacted by academic leadership in the absence of an institutional program and could serve as a guide to individuals in academia aspiring to address diversity and inclusion in STEMM.

Impellizzeri, FM, Marcora, SM & Coutts, AJ 2019, 'Internal and External Training Load: 15 Years On', International Journal of Sports Physiology and Performance, vol. 14, no. 2, pp. 270-273.
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© 2019 Human Kinetics, Inc. Exercise is a stressor that induces various psychophysiological responses, which mediate cellular adaptations in many organ systems. To maximize this adaptive response, coaches and scientists need to control the stress applied to the athlete at the individual level. To achieve this, precise control and manipulation of the training load are required. In 2003, the authors introduced a theoretical framework to define and conceptualize the measurable constructs of the training process. They described training load as having 2 measurable components: internal and external load. The aim of this commentary is to extend, clarify, and refine both the theoretical framework and the definitions of internal and external training load to avoid misinterpretation of this concept.

Jacobs, C, White, S & Phillips, J 2019, 'Genetics in palliative care: too much to ask?', International Journal of Palliative Nursing, vol. 25, no. 5, pp. 212-214.
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People with an inherited condition who receive palliative care may be missing out on the opportunity to store a DNA sample for future use by their families and offspring. A DNA sample from a family member affected with an inherited condition can help at-risk relatives to access accurate risk assessment and, where relevant, enhanced surveillance and risk-reducing measures. As genetic and genomic testing becomes increasingly important in all aspects of healthcare, health professionals specialising in palliative care will be asked to communicate about family history risk and testing. This article highlights the importance of discussing genetics and genomics issues for people receiving palliative care, their families and the health professionals caring for them.

Jones, PM, Mazzio, E, Soliman, K & George, AM 2019, 'In Silico Investigation of the Binding of MCoTI-II Plant Defense Knottin to the γ-NGF Serine Protease of the 7S Nerve Growth Factor Complex and Biological Activity of Its NGF Mimetic Properties', The Journal of Physical Chemistry B, vol. 123, no. 43, pp. 9104-9110.
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Kaasalainen, S, Sussman, T, McCleary, L, Thompson, G, Hunter, P, Wickson-Griffiths, A, Cook, R, Bello-Haas, VD, Venturato, L, Papaioannou, A, You, J & Parker, D 2019, 'A Stakeholder Analysis of the Strengthening a Palliative Approach in Long-Term Care Model', Canadian Journal of Nursing Leadership, vol. 32, no. 3, pp. 27-39.
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Copyright © 2019 Longwoods Publishing. OBJECTIVE: The purpose of this study was to conduct a stakeholder analysis of the strengthening a palliative approach to long-term care (SPA-LTC) model and refine it based on feedback from long-term care (LTC) residents and their families, staff, researchers and decision makers. METHODS: We used a mixed-methods design to conduct a stakeholder analysis of the SPA-LTC model that consisted of two sequential components: qualitative focus groups with LTC staff followed by a quantitative survey with key stakeholders. RESULTS: Twenty-one LTC staff provided feedback about the SPA-LTC model after residents relocated to LTC, during advanced illness and at end of life and in the period of grief and bereavement. This feedback helped to guide revisions of the model. According to the survey results, the SPA-LTC model was well received by 35 stakeholders, but its feasibility was questioned. CONCLUSION: The Canadian SPA-LTC model is evidence based and endorsed by LTC staff and stakeholders. Efforts are needed to determine the feasibility of implementing the model to ensure that residents' needs are made a priority while in LTC.

Kaasalainen, S, Sussman, T, McCleary, L, Thompson, G, Hunter, P, Wickson-Griffiths, A, Cook, R, Bello-Haas, VD, Venturato, L, Papaioannou, A, You, J & Parker, D 2019, 'Palliative Care Models in Long-Term Care: A Scoping Review', Canadian Journal of Nursing Leadership, vol. 32, no. 3, pp. 8-26.
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Copyright © 2019 Longwoods Publishing. OBJECTIVE: The goal of this scoping review was to identify existing palliative models in long-term care (LTC) homes and differentiate between the key components of each in terms of training/capacity-building strategies; resident, family and staff support; and advance care planning (ACP) and goals-of-care discussions. METHODS: We conducted a scoping review based on established methods to summarize the international literature on palliative models and programs for LTC. We analyzed the data using tabular summaries and content analysis. RESULTS: We extracted data from 46 articles related to palliative programs, training/capacity building, family support, ACP and goals of care. Study results highlighted that three key components are needed in a palliative program in LTC: (1) training and capacity building; (2) support for residents, family and staff; and (3) ACP, goals-of-care discussion and informed consent. CONCLUSION: This scoping review provided important information about key components to be included in a palliative program in LTC. Future work is needed to develop a model that suits the unique characteristics in the Canadian context.

Karacan, I, Ben-Nissan, B, Wang, HA, Juritza, A, Swain, MV, Müller, WH, Chou, J, Stamboulis, A, Macha, IJ & Taraschi, V 2019, 'Mechanical testing of antimicrobial biocomposite coating on metallic medical implants as drug delivery system', Materials Science and Engineering: C, vol. 104, no. 109757, pp. 109757-109757.
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Khan, TA & Ling, SH 2019, 'Review on Electrical Impedance Tomography: Artificial Intelligence Methods and its Applications', Algorithms, vol. 12, no. 5, pp. 88-88.
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Electrical impedance tomography (EIT) has been a hot topic among researchers for the last 30 years. It is a new imaging method and has evolved over the last few decades. By injecting a small amount of current, the electrical properties of tissues are determined and measurements of the resulting voltages are taken. By using a reconstructing algorithm these voltages then transformed into a tomographic image. EIT contains no identified threats and as compared to magnetic resonance imaging (MRI) and computed tomography (CT) scans (imaging techniques), it is cheaper in cost as well. In this paper, a comprehensive review of efforts and advancements undertaken and achieved in recent work to improve this technology and the role of artificial intelligence to solve this non-linear, ill-posed problem are presented. In addition, a review of EIT clinical based applications has also been presented.

Khawwaf, J, Zheng, J, Chai, R, Lu, R & Man, Z 2019, 'Adaptive Microtracking Control for an Underwater IPMC Actuator Using New Hyperplane-Based Sliding Mode', IEEE/ASME Transactions on Mechatronics, vol. 24, no. 5, pp. 2108-2117.
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Khoo, WH, Ledergor, G, Weiner, A, Roden, DL, Terry, RL, McDonald, MM, Chai, RC, De Veirman, K, Owen, KL, Opperman, KS, Vandyke, K, Clark, JR, Seckinger, A, Kovacic, N, Nguyen, A, Mohanty, ST, Pettitt, JA, Xiao, Y, Corr, AP, Seeliger, C, Novotny, M, Lasken, RS, Nguyen, TV, Oyajobi, BO, Aftab, D, Swarbrick, A, Parker, B, Hewett, DR, Hose, D, Vanderkerken, K, Zannettino, ACW, Amit, I, Phan, TG & Croucher, PI 2019, 'A niche-dependent myeloid transcriptome signature defines dormant myeloma cells', Blood, vol. 134, no. 1, pp. 30-43.
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AbstractThe era of targeted therapies has seen significant improvements in depth of response, progression-free survival, and overall survival for patients with multiple myeloma. Despite these improvements in clinical outcome, patients inevitably relapse and require further treatment. Drug-resistant dormant myeloma cells that reside in specific niches within the skeleton are considered a basis of disease relapse but remain elusive and difficult to study. Here, we developed a method to sequence the transcriptome of individual dormant myeloma cells from the bones of tumor-bearing mice. Our analyses show that dormant myeloma cells express a distinct transcriptome signature enriched for immune genes and, unexpectedly, genes associated with myeloid cell differentiation. These genes were switched on by coculture with osteoblastic cells. Targeting AXL, a gene highly expressed by dormant cells, using small-molecule inhibitors released cells from dormancy and promoted their proliferation. Analysis of the expression of AXL and coregulated genes in human cohorts showed that healthy human controls and patients with monoclonal gammopathy of uncertain significance expressed higher levels of the dormancy signature genes than patients with multiple myeloma. Furthermore, in patients with multiple myeloma, the expression of this myeloid transcriptome signature translated into a twofold increase in overall survival, indicating that this dormancy signature may be a marker of disease progression. Thus, engagement of myeloma cells with the osteoblastic niche induces expression of a suite of myeloid genes that predicts disease progression and that comprises potential drug targets to eradicate dormant myeloma cells.

Khorsand, M, Tavakoli, J, Kamanya, K & Tang, Y 2019, 'Simulation of high-output and lightweight sliding-mode triboelectric nanogenerators', Nano Energy, vol. 66, pp. 104115-104115.
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In light of the rapid growth in microelectronic technology, triboelectric nanogenerators (TENGs) have been exploited as securely sustainable substitutes for energy scavenging purposes as well as self-powered sensory utilization. In essence, TENGs’ energy output and average power distribution depend highly on certain key parameters including contact area, the thickness of electric films and external resistance. This study attempts to predict the behavior of TENGs based on variation of those key parameters and tries to optimize the associated characteristics leading to high-output and light-weight sliding-mode TENGs. To meet this problem, an artificial intelligence approach is taken into consideration and solutions for load resistance and geometry are presented. Furthermore, an experimental setup is designed to evaluate the accuracy of the simulation results, demonstrating the precision of the applied theory. The results revealed that the predefined sliding-mode TENG can harvest 0.25 mJ at each cycle in an open-circuit condition where the weight is almost 42.91 g. Moreover, simulation proves that an appropriate value for the external resistor can increase the scavenged energy up to 3.65 mJ at each reciprocal movement. Finally, temporal responses for charge, current, voltage, power output, and harvested energy are plotted and discussed, facilitating understanding of the relationship between scavenged energy and optimized parameters.

Khuat, TT & Gabrys, B 2019, 'A comparative study of general fuzzy min-max neural networks for pattern classification problems', Neurocomputing, 2019, vol. 386, pp. 110-125.
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General fuzzy min-max (GFMM) neural network is a generalization of fuzzyneural networks formed by hyperbox fuzzy sets for classification and clusteringproblems. Two principle algorithms are deployed to train this type of neuralnetwork, i.e., incremental learning and agglomerative learning. This paperpresents a comprehensive empirical study of performance influencing factors,advantages, and drawbacks of the general fuzzy min-max neural network onpattern classification problems. The subjects of this study include (1) theimpact of maximum hyperbox size, (2) the influence of the similarity thresholdand measures on the agglomerative learning algorithm, (3) the effect of datapresentation order, (4) comparative performance evaluation of the GFMM withother types of fuzzy min-max neural networks and prevalent machine learningalgorithms. The experimental results on benchmark datasets widely used inmachine learning showed overall strong and weak points of the GFMM classifier.These outcomes also informed potential research directions for this class ofmachine learning algorithms in the future.

Khuat, TT, Chen, F & Gabrys, B 2019, 'An Effective Multi-Resolution Hierarchical Granular Representation based Classifier using General Fuzzy Min-Max Neural Network', IEEE Transactions on Fuzzy Systems, pp. 1-1, 2019, vol. 29, no. 2, pp. 427-441.
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Motivated by the practical demands for simplification of data towards beingconsistent with human thinking and problem solving as well as tolerance ofuncertainty, information granules are becoming important entities in dataprocessing at different levels of data abstraction. This paper proposes amethod to construct classifiers from multi-resolution hierarchical granularrepresentations (MRHGRC) using hyperbox fuzzy sets. The proposed approach formsa series of granular inferences hierarchically through many levels ofabstraction. An attractive characteristic of our classifier is that it canmaintain relatively high accuracy at a low degree of granularity based onreusing the knowledge learned from lower levels of abstraction. In addition,our approach can reduce the data size significantly as well as handling theuncertainty and incompleteness associated with data in real-world applications.The construction process of the classifier consists of two phases. The firstphase is to formulate the model at the greatest level of granularity, while thelater stage aims to reduce the complexity of the constructed model and deduceit from data at higher abstraction levels. Experimental outcomes conductedcomprehensively on both synthetic and real datasets indicated the efficiency ofour method in terms of training time and predictive performance in comparisonto other types of fuzzy min-max neural networks and common machine learningalgorithms.

Khuat, TT, Ruta, D & Gabrys, B 2019, 'Hyperbox based machine learning algorithms: A comprehensive survey', Soft Computing, vol. 25, no. 2, pp. 1325-1363.
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With the rapid development of digital information, the data volume generatedby humans and machines is growing exponentially. Along with this trend, machinelearning algorithms have been formed and evolved continuously to discover newinformation and knowledge from different data sources. Learning algorithmsusing hyperboxes as fundamental representational and building blocks are abranch of machine learning methods. These algorithms have enormous potentialfor high scalability and online adaptation of predictors built using hyperboxdata representations to the dynamically changing environments and streamingdata. This paper aims to give a comprehensive survey of literature onhyperbox-based machine learning models. In general, according to thearchitecture and characteristic features of the resulting models, the existinghyperbox-based learning algorithms may be grouped into three major categories:fuzzy min-max neural networks, hyperbox-based hybrid models, and otheralgorithms based on hyperbox representations. Within each of these groups, thispaper shows a brief description of the structure of models, associated learningalgorithms, and an analysis of their advantages and drawbacks. Mainapplications of these hyperbox-based models to the real-world problems are alsodescribed in this paper. Finally, we discuss some open problems and identifypotential future research directions in this field.

Koach, J, Holien, JK, Massudi, H, Carter, DR, Ciampa, OC, Herath, M, Lim, T, Seneviratne, JA, Milazzo, G, Murray, JE, McCarroll, JA, Liu, B, Mayoh, C, Keenan, B, Stevenson, BW, Gorman, MA, Bell, JL, Doughty, L, Hüttelmaier, S, Oberthuer, A, Fischer, M, Gifford, AJ, Liu, T, Zhang, X, Zhu, S, Gustafson, WC, Haber, M, Norris, MD, Fletcher, JI, Perini, G, Parker, MW, Cheung, BB & Marshall, GM 2019, 'Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 Binding Interface', Cancer Research, vol. 79, no. 21, pp. 5652-5667.
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Abstract MYCN is a major driver for the childhood cancer, neuroblastoma, however, there are no inhibitors of this target. Enhanced MYCN protein stability is a key component of MYCN oncogenesis and is maintained by multiple feedforward expression loops involving MYCN transactivation target genes. Here, we reveal the oncogenic role of a novel MYCN target and binding protein, proliferation-associated 2AG4 (PA2G4). Chromatin immunoprecipitation studies demonstrated that MYCN occupies the PA2G4 gene promoter, stimulating transcription. Direct binding of PA2G4 to MYCN protein blocked proteolysis of MYCN and enhanced colony formation in a MYCN-dependent manner. Using molecular modeling, surface plasmon resonance, and mutagenesis studies, we mapped the MYCN–PA2G4 interaction site to a 14 amino acid MYCN sequence and a surface crevice of PA2G4. Competitive chemical inhibition of the MYCN–PA2G4 protein–protein interface had potent inhibitory effects on neuroblastoma tumorigenesis in vivo. Treated tumors showed reduced levels of both MYCN and PA2G4. Our findings demonstrate a critical role for PA2G4 as a cofactor in MYCN-driven neuroblastoma and highlight competitive inhibition of the PA2G4-MYCN protein binding as a novel therapeutic strategy in the disease. Significance: Competitive chemical inhibition of the PA2G4–MYCN protein interface provides a basis for drug design of small molecules targeting MYC and MYCN-binding partners in malignancies driven by MYC family oncoproteins.

Kulasinghe, A, Kapeleris, J, Cooper, C, Warkiani, ME, O’Byrne, K & Punyadeera, C 2019, 'Phenotypic Characterization of Circulating Lung Cancer Cells for Clinically Actionable Targets', Cancers, vol. 11, no. 3, pp. 380-380.
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Objectives: In non-small cell lung cancers (NSCLC), tumour biopsy can often be an invasive procedure. The development of a non-invasive methodology to study genetic changes via circulating tumour cells (CTCs) is an appealing concept. Whilst CTCs typically remain as rare cells, improvements in epitope-independent CTC isolation techniques has given rise to a greater capture of CTCs. In this cross sectional study, we demonstrate the capture and characterization of NSCLC CTCs for the clinically actionable markers epidermal growth factor receptor (EGFR) alterations, anaplastic lymphoma kinase (ALK) rearrangements and programmed death ligand-1 (PD-L1) expression. The study identified CTCs/CTC clusters in 26/35 Stage IV NSCLC patients, and subsequently characterized the CTCs for EGFR mutation, ALK status and PD-L1 status. This pilot study demonstrates the potential of a non-invasive fluid biopsy to determine clinically relevant biomarkers in NSCLC.

Laffer, JC, Coutts, AJ & Fransen, J 2019, 'Effect of Skill Level on Allocation of Visual Attention in Volleyball Blocking', Journal of Motor Learning and Development, vol. 7, no. 2, pp. 215-231.
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Dynamic motor skills such as volleyball blocking rely on efficient perception–action coupling and are influenced by individual, environmental, and task constraints. However, limited research studies have assessed the effect of an individual constraint such as blocking skill on visual attention during an in-situ volleyball blocking task. Therefore, this study used a cross-sectional, observational design to investigate the gaze behavior of 18 male volleyball players (25.6 ± 4.9 years), of two different levels of blocking skill determined a priori according to success during an on-court blocking task. When compared to relatively unsuccessful players (RUS), the gaze of relatively successful players (RS) was observed to fixate more often (RUS: 0.7 ± 0.7 n, RS: 1.3 ± 0.3 n) and dwell for longer (Total; RUS: 12.2 ± 18.4%, RS: 48.0 ± 37.2%, Phase 4; RUS: 6.6 ± 8.8%, RS: 16.9 ± 12.4%) on the opposition spiker, demonstrating that important perceptual information about an opposing team’s attack lies within the behavior of the opposition spiker. More successful blockers were also observed to be taller (RUS: 181.8 ± 6.6 cm, RS: 192.6 ± 3.9 cm), longer in arm-span (RUS: 185.7 ± 5.6 cm, RS: 195.2 ± 5.6 cm), and heavier (RUS: 78.6 ± 11.4 kg, RS: 90.5 ± 8.5 kg). These results can consequently be used to develop a profile of the visual attention and physical attributes of successful blockers for use in developing talented players.

Lagad, A, Hodgkinson, K & Newton‐John, TRO 2019, 'Is ignorance bliss, or is knowledge power? When cancer healthcare professionals become cancer patients', European Journal of Cancer Care, vol. 28, no. 4.
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© 2019 John Wiley & Sons Ltd Cancer healthcare professionals who are diagnosed with cancer enter the patient journey with considerable illness-specific and healthcare expertise, which may influence the nature of their experience. Insights gained from having personal cancer experience may also lead to changes in professionals' subsequent clinical practice. This study explored cancer professional-patients' experiences of their own cancer diagnosis, changes in practice, and recommendations for cancer care improvements. Participants were current or former cancer healthcare professionals who had ever received a cancer diagnosis. Semi-structured interviews were conducted with 26 participants. Thematic analysis with an inductive approach was used for data analysis. Cancer professional-patients faced unique needs, benefits and disadvantages due to their professional background, which both aided and marred their personal cancer experience. Individuals reported subjective practical and emotional-related improvements in their clinical practice, although adverse emotional consequences upon returning to work were also prevalent. Care recommendations highlighted the importance of communication skills training for professionals, integrating psychological support, and providing patient-centred care. In order to provide optimal care for cancer professional-patients, providers must acknowledge their distinct challenges. Findings may help to foster improvements in cancer care practices through developing guidelines for treating cancer professional-patients, and as part of narrative-based medicine.

Lan, C, Peng, H, Hutvagner, G & Li, J 2019, 'Construction of competing endogenous RNA networks from paired RNA-seq data sets by pointwise mutual information', BMC Genomics, vol. 20, no. S9, p. 943.
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Abstract Background A long noncoding RNA (lncRNA) can act as a competing endogenous RNA (ceRNA) to compete with an mRNA for binding to the same miRNA. Such an interplay between the lncRNA, miRNA, and mRNA is called a ceRNA crosstalk. As an miRNA may have multiple lncRNA targets and multiple mRNA targets, connecting all the ceRNA crosstalks mediated by the same miRNA forms a ceRNA network. Methods have been developed to construct ceRNA networks in the literature. However, these methods have limits because they have not explored the expression characteristics of total RNAs. Results We proposed a novel method for constructing ceRNA networks and applied it to a paired RNA-seq data set. The first step of the method takes a competition regulation mechanism to derive candidate ceRNA crosstalks. Second, the method combines a competition rule and pointwise mutual information to compute a competition score for each candidate ceRNA crosstalk. Then, ceRNA crosstalks which have significant competition scores are selected to construct the ceRNA network. The key idea, pointwise mutual information, is ideally suitable for measuring the complex point-to-point relationships embedded in the ceRNA networks. Conclusion Computational experiments and results demonstrate that the ceRNA networks can capture important regulatory mechanism of breast cancer, and have also revealed new insights into the treatment of breast cancer. The proposed method can be directly applied to other RNA-seq data sets for deeper disease understanding.

Le, NT & Hoang, DB 2019, 'A Threat Computation Model using a Markov Chain and Common Vulnerability Scoring System and its Application to Cloud Security', Journal of Telecommunications and the Digital Economy, vol. 7, no. 1, pp. 37-56.
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Securing cyber infrastructures has become critical because they are increasingly exposed to attackers while accommodating a huge number of IoT devices and supporting numerous sophisticated emerging applications. Security metrics are essential for assessing the security risks and making effective decisions concerning system security. Many security metrics rely on mathematical models, but are mainly based on empirical data, qualitative methods, or compliance checking, and this renders the outcome far from satisfactory. Computing the probability of an attack, or more precisely a threat that materialises into an attack, forms an essential basis for a quantitative security metric. This paper proposes a novel approach to compute the probability distribution of cloud security threats based on a Markov chain and Common Vulnerability Scoring System. Moreover, the paper introduces the method to estimate the probability of security attacks. The use of the new security threat model and its computation is demonstrated through their application to estimating the probabilities of cloud threats and types of attacks.

Li, A, Geyer, FC, Blecua, P, Lee, JY, Selenica, P, Brown, DN, Pareja, F, Lee, SSK, Kumar, R, Rivera, B, Bi, R, Piscuoglio, S, Wen, HY, Lozada, JR, Gularte-Mérida, R, Cavallone, L, Aghmesheh, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Blackburn, A, Bogwitz, M, Brown, M, Burgess, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Christian, A, Clarke, C, Cohen, P, Crook, A, Cui, J, Cummings, M, Dawson, S-J, De Fazio, A, Delatycki, M, Dobrovic, A, Dudding, T, Duijf, P, Edkins, E, Edwards, S, Farshid, G, Fellows, A, Field, M, Flanagan, J, Fong, P, Forbes, J, Forrest, L, Fox, S, French, J, Friedlander, M, Ortega, DG, Gattas, M, Giles, G, Gill, G, Gleeson, M, Greening, S, Haan, E, Harris, M, Hayward, N, Hickie, I, Hopper, J, Hunt, C, James, P, Jenkins, M, Kefford, R, Kentwell, M, Kirk, J, Kollias, J, Lakhani, S, Lindeman, G, Lipton, L, Lobb, L, Lok, S, Macrea, F, Mann, G, Marsh, D, McLachlan, S-A, Meiser, B, Milne, R, Nightingale, S, O’Connell, S, Pachter, N, Patterson, B, Phillips, K, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Scott, R, Sexton, A, Shelling, A, Simpson, P, Spigelman, A, Spurdle, M, Stone, J, Taylor, J, Thorne, H, Trainer, A, Trench, G, Tucker, K, Visvader, J, Walker, L, Wallis, M, Williams, R, Winship, I, Wu, K, Young, MA, Rezoug, Z, Nguyen-Dumont, T, Peterlongo, P, Tondini, C, Terkelsen, T, Rønlund, K, Boonen, SE, Mannerma, A, Winqvist, R, Janatova, M, Rajadurai, P, Xia, B, Norton, L, Robson, ME, Ng, P-S, Looi, L-M, Southey, MC, Weigelt, B, Soo-Hwang, T, Tischkowitz, M, Foulkes, WD & Reis-Filho, JS 2019, 'Publisher Correction: Homologous recombination DNA repair defects in PALB2-associated breast cancers', npj Breast Cancer, vol. 5, no. 1.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Li, A, Geyer, FC, Blecua, P, Lee, JY, Selenica, P, Brown, DN, Pareja, F, Lee, SSK, Kumar, R, Rivera, B, Bi, R, Piscuoglio, S, Wen, HY, Lozada, JR, Gularte-Mérida, R, Cavallone, L, Rezoug, Z, Nguyen-Dumont, T, Peterlongo, P, Tondini, C, Terkelsen, T, Rønlund, K, Boonen, SE, Mannerma, A, Winqvist, R, Janatova, M, Rajadurai, P, Xia, B, Norton, L, Robson, ME, Ng, P-S, Looi, L-M, Southey, MC, Weigelt, B, Soo-Hwang, T, Tischkowitz, M, Foulkes, WD, Reis-Filho, JS, Aghmesheh, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Blackburn, A, Bogwitz, M, Brown, M, Burgess, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Christian, A, Clarke, C, Cohen, P, Crook, A, Cui, J, Cummings, M, Dawson, S-J, De Fazio, A, Delatycki, M, Dobrovic, A, Dudding, T, Duijf, P, Edkins, E, Edwards, S, Farshid, G, Fellows, A, Field, M, Flanagan, J, Fong, P, Forbes, J, Forrest, L, Fox, S, French, J, Friedlander, M, Ortega, DG, Gattas, M, Giles, G, Gill, G, Gleeson, M, Greening, S, Haan, E, Harris, M, Hayward, N, Hickie, I, Hopper, J, Hunt, C, James, P, Jenkins, M, Kefford, R, Kentwell, M, Kirk, J, Kollias, J, Lakhani, S, Lindeman, G, Lipton, L, Lobb, L, Lok, S, Macrea, F, Mann, G, Marsh, D, McLachlan, S-A, Meiser, B, Milne, R, Nightingale, S, O’Connell, S, Pachter, N, Patterson, B, Phillips, K, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Scott, R, Sexton, A, Shelling, A, Simpson, P, Spigelman, A, Spurdle, M, Stone, J, Taylor, J, Thorne, H, Trainer, A, Trench, G, Tucker, K, Visvader, J, Walker, L, Wallis, M, Williams, R, Winship, I, Wu, K & Young, MA 2019, 'Homologous recombination DNA repair defects in PALB2-associated breast cancers', npj Breast Cancer, vol. 5, no. 1.
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AbstractMono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2

Li, G, Chan, YL, Nguyen, LT, Mak, C, Zaky, A, Anwer, AG, Shi, Y, Nguyen, T, Pollock, CA, Oliver, BG, Saad, S & Chen, H 2019, 'Impact of maternal e‐cigarette vapor exposure on renal health in the offspring', Annals of the New York Academy of Sciences, vol. 1452, no. 1, pp. 65-77.
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AbstractMaternal smoking during pregnancy is a significant risk factor of renal pathology in the offspring. E‐cigarettes are perceived to be a safe option and are increasingly used by pregnant women either continuously during pregnancy or as a replacement for tobacco cigarettes. This study aimed to determine the effects of replacing tobacco cigarettes with e‐cigarettes during pregnancy, and continuous e‐cigarette use during pregnancy on the offspring's kidneys. Female Balb/c mice were exposed to either air (sham) or tobacco cigarette smoke (SE) for 6 weeks prior to mating, during gestation and lactation. A subset of the “SE group” received e‐cigarette vapor (containing nicotine) after mating until pups weaned. Additional female mice were continuously exposed to e‐vapor (either with or without nicotine) for 6 weeks prior to mating until pups weaned. Kidneys and urine from the male offspring were assessed at postnatal day 1, day 20 (weaning), and 13 weeks of age (adulthood). E‐cigarette replacement was less detrimental to renal development and albuminuria than continuous SE during pregnancy. However, continuous e‐vapor exposure during pregnancy increased markers of oxidative stress, inflammation, and fibrosis in the adult offspring, independent of nicotine. E‐cigarette use during pregnancy confers future risk to the offspring's kidneys.

Li, G, Chan, YL, Sukjamnong, S, Anwer, AG, Vindin, H, Padula, M, Zakarya, R, George, J, Oliver, BG, Saad, S & Chen, H 2019, 'A Mitochondrial Specific Antioxidant Reverses Metabolic Dysfunction and Fatty Liver Induced by Maternal Cigarette Smoke in Mice', Nutrients, vol. 11, no. 7, pp. 1669-1669.
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Maternal smoking leads to glucose and lipid metabolic disorders and hepatic damage in the offspring, potentially due to mitochondrial oxidative stress. Mitoquinone mesylate (MitoQ) is a mitochondrial targeted antioxidant with high bioavailability. This study aimed to examine the impact of maternal cigarette smoke exposure (SE) on offspring’s metabolic profile and hepatic damage, and whether maternal MitoQ supplementation during gestation can affect these changes. Female Balb/c mice (eight weeks) were either exposed to air or SE for six weeks prior to mating and throughout gestation and lactation. A subset of the SE dams were supplied with MitoQ in the drinking water (500 µmol/L) during gestation and lactation. Intraperitoneal glucose tolerance test was performed in the male offspring at 12 weeks and the livers and plasma were collected at 13 weeks. Maternal SE induced glucose intolerance, hepatic steatosis, mitochondrial oxidative stress and related damage in the adult offspring. Maternal MitoQ supplementation reduced hepatic mitochondrial oxidative stress and improved markers of mitophagy and mitochondrial biogenesis. This may restore hepatic mitochondrial health and was associated with an amelioration of glucose intolerance, hepatic steatosis and pathological changes induced by maternal SE. MitoQ supplementation may potentially prevent metabolic dysfunction and hepatic pathology induced by intrauterine SE.

Lim, CED, Ng, RWC, Cheng, NCL, Zhang, GS & Chen, H 2019, 'Acupuncture for polycystic ovarian syndrome', Cochrane Database of Systematic Reviews, vol. 2019, no. 7, p. CD007689.
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© 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea, infertility and hirsutism. Conventional treatment of PCOS includes a range of oral pharmacological agents, lifestyle changes and surgical modalities. Beta-endorphin is present in the follicular fluid of both normal and polycystic ovaries. It was demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture impacts on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction via increased beta-endorphin production effecting GnRH secretion. This is an update of our previous review published in 2016. Objectives To assess the effectiveness and safety of acupuncture treatment for oligo/anovulatory women with polycystic ovarian syndrome (PCOS) for both fertility and symptom control. Search methods We identified relevant studies from databases including the Gynaecology and Fertility Group Specialised Register, CENTRAL, MED-LINE, Embase, PsycINFO, CNKI, CBM and VIP. We also searched trial registries and reference lists from relevant papers. CENTRAL, MEDLINE, Embase, PsycINFO, CNKI and VIP searches are current to May 2018. CBM database search is to November 2015. Selection criteria We included randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for oligo/anovulatory women with PCOS. We excluded quasi-or pseudo-RCTs. Data collection and analysis Two review authors independently selected the studies, extracted data and assessed risk of bias. We calculated risk ratios (RR), mean difference (MD), standardised mean difference (SMD) and 95% confidence intervals (CIs). Primary outcomes were live birth rate, multi...

Liu, G, Cooley, MA, Jarnicki, AG, Borghuis, T, Nair, PM, Tjin, G, Hsu, AC, Haw, TJ, Fricker, M, Harrison, CL, Jones, B, Hansbro, NG, Wark, PA, Horvat, JC, Argraves, WS, Oliver, BG, Knight, DA, Burgess, JK & Hansbro, PM 2019, 'Fibulin-1c regulates transforming growth factor–β activation in pulmonary tissue fibrosis', JCI Insight, vol. 4, no. 16.
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Copyright: © 2019, American Society for Clinical Investigation. Tissue remodeling/fibrosis is a major feature of all fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). It is underpinned by accumulating extracellular matrix (ECM) proteins. Fibulin-1c (Fbln1c) is a matricellular ECM protein associated with lung fibrosis in both humans and mice and stabilizes collagen formation. Here we discovered that Fbln1c was increased in the lung tissues of patients with IPF and experimental bleomycin-induced pulmonary fibrosis. Fbln1c-deficient (Fbln1c–/–) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin, and tenascin-C in collagen deposits following bleomycin challenge. In a potentially novel mechanism of fibrosis, Fbln1c bound to latent TGF-β–binding protein 1 (LTBP1) to induce TGF-β activation and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1c and LTBP1 colocalized in lung tissues from patients with IPF. Thus, Fbln1c may be a novel driver of TGF-β–induced fibrosis involving LTBP1 and may be an upstream therapeutic target.

Liu, PY, Tee, AE, Milazzo, G, Hannan, KM, Maag, J, Mondal, S, Atmadibrata, B, Bartonicek, N, Peng, H, Ho, N, Mayoh, C, Ciaccio, R, Sun, Y, Henderson, MJ, Gao, J, Everaert, C, Hulme, AJ, Wong, M, Lan, Q, Cheung, BB, Shi, L, Wang, JY, Simon, T, Fischer, M, Zhang, XD, Marshall, GM, Norris, MD, Haber, M, Vandesompele, J, Li, J, Mestdagh, P, Hannan, RD, Dinger, ME, Perini, G & Liu, T 2019, 'The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35', Nature Communications, vol. 10, no. 1.
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AbstractThe majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.

Liu, T, Zhang, W, Ye, L, Ueland, M, Forbes, SL & Su, SW 2019, 'A novel multi-odour identification by electronic nose using non-parametric modelling-based feature extraction and time-series classification', Sensors and Actuators B: Chemical, vol. 298, pp. 126690-126690.
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© 2019 Elsevier B.V. The electronic nose (e-nose) is an olfaction system that consists of an array of chemical sensors and effective machine learning algorithms for the detection of various target odours. Feature extraction and classification methods are of great importance in improving the performance of the e-nose system. In this paper, a novel odour identification method is presented. Firstly, we use the kernel-based system modelling approach to extract odour features. Its solution is a series of finite impulse responses which containing discriminant information of different odours. In addition, a parameter optimisation method based on normalised mean square error and information entropy is proposed to optimise the kernel function. The entropy is effective in preventing the finite impulse responses from overfitting. Multi-odour classification is achieved based on Gaussian mixture density hidden Markov model (GMM-HMM) considering the characteristic of the extracted features. Also, parameter selection for GMM-HMM is realised according to BIC index and cross-validation. Then, we validate the performance of the proposed feature extraction method in resistance to noise and compare it with other existed features. The modelling-based feature reached the highest performance even without applying any filtering or smoothing techniques. Finally, we compare the proposed combination of feature extraction and classification algorithms with other approaches. The proposed method outperformed other approaches reaching 93.56% in sensitivity and 98.71% in specificity. The results demonstrate that the proposed method is applicable in e-nose-based odour identification.

Liu, Y, Yu, Z, Dinger, ME & Li, J 2019, 'Index suffix–prefix overlaps by (w, k)-minimizer to generate long contigs for reads compression', Bioinformatics, vol. 35, no. 12, pp. 2066-2074.
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Abstract Motivation Advanced high-throughput sequencing technologies have produced massive amount of reads data, and algorithms have been specially designed to contract the size of these datasets for efficient storage and transmission. Reordering reads with regard to their positions in de novo assembled contigs or in explicit reference sequences has been proven to be one of the most effective reads compression approach. As there is usually no good prior knowledge about the reference sequence, current focus is on the novel construction of de novo assembled contigs. Results We introduce a new de novo compression algorithm named minicom. This algorithm uses large k-minimizers to index the reads and subgroup those that have the same minimizer. Within each subgroup, a contig is constructed. Then some pairs of the contigs derived from the subgroups are merged into longer contigs according to a (w, k)-minimizer-indexed suffix–prefix overlap similarity between two contigs. This merging process is repeated after the longer contigs are formed until no pair of contigs can be merged. We compare the performance of minicom with two reference-based methods and four de novo methods on 18 datasets (13 RNA-seq datasets and 5 whole genome sequencing datasets). In the compression of single-end reads, minicom obtained the smallest file size for 22 of 34 cases with significant improvement. In the compression of paired-end reads, minicom achieved 20–80% compression gain over the best state-of-the-art algorithm. Our method also achieved a 10% size reduction of compressed files in comparison with the best algorithm under the reads-order preserving mode. These excellent performances are mainly attributed to the exploit of the redund...

Liu, Y, Zhang, LY & Li, J 2019, 'Fast detection of maximal exact matches via fixed sampling of queryK-mers and Bloom filtering of indexK-mers', Bioinformatics, vol. 35, no. 22, pp. 4560-4567.
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AbstractMotivationDetection of maximal exact matches (MEMs) between two long sequences is a fundamental problem in pairwise reference-query genome comparisons. To efficiently compare larger and larger genomes, reducing the number of indexed k-mers as well as the number of query k-mers has been adopted as a mainstream approach which saves the computational resources by avoiding a significant number of unnecessary matches.ResultsUnder this framework, we proposed a new method to detect all MEMs from a pair of genomes. The method first performs a fixed sampling of k-mers on the query sequence, and adds these selected k-mers to a Bloom filter. Then all the k-mers of the reference sequence are tested by the Bloom filter. If a k-mer passes the test, it is inserted into a hash table for indexing. Compared with the existing methods, much less number of query k-mers are generated and much less k-mers are inserted into the index to avoid unnecessary matches, leading to an efficient matching process and memory usage savings. Experiments on large genomes demonstrate that our method is at least 1.8 times faster than the best of the existing algorithms. This performance is mainly attributed to the key novelty of our method that the fixed k-mer sampling must be conducted on the query sequence and the index k-mers are filtered from the reference sequence via a Bloom filter.Availability and implementationhttps://github.com/yuansliu/bfMEMSupplementary informationSupplementary data are available at Bioinformatics online.

Lovell, M, Birch, M-R, Luckett, T, Phillips, J, Davidson, PM, Agar, M & Boyle, F 2019, 'Screening and Audit as Service-Level Strategies to Support Implementation of Australian Guidelines for Cancer Pain Management in Adults: A Feasibility Study', Pain Management Nursing, vol. 20, no. 2, pp. 113-117.
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BACKGROUND:Pain in people with cancer is common but often under-recognized and under-treated. Guidelines can improve the quality of pain care, but need targeted strategies to support implementation. AIM:To test the feasibility of two service-level strategies for supporting guideline implementation: a screening system and medical record audit. DESIGN:Multimethods. SETTING:One oncology outpatient service, and one palliative care outpatient and inpatient service. PARTICIPANTS:Patients with advanced cancer. METHODS:Patients were screened in the waiting room with a modified version of the Edmonton Symptom Assessment System-revised either electronically or in paper-based format. Feasibility indicated the percentage of patients successfully screened from the total number attending the services. An audit assessed adherence to key indicators of pain assessment and management. Feasibility thresholds were set at 75% incidence for screening and a median of 30 minutes per patient for audit. RESULTS:Of 452 patient visits, 95% (n = 429) were successfully screened, 34% (n = 155) electronically and 61% (n = 274) paper-based. Electronic pain screening was technically challenging and time-intensive for nurses. Thirty-one patients consented to have their records audited. The median audit time was 37.5 minutes (range 10-120 minutes). Variability arose from the number and type of record (outpatient or inpatient). Adherence to indicators varied from 63% (pain assessment at first presentation) to 94% (regular pain assessment and medication prescribed at regular intervals). CONCLUSIONS:This study confirmed the need to implement evidence-based guidelines for cancer pain and generated useful insights into the feasibility of pain screening and audit.

Lovell, TWJ, Fransen, J, Bocking, CJ & Coutts, AJ 2019, 'Factors affecting sports involvement in a school-based youth cohort: Implications for long-term athletic development', Journal of Sports Sciences, vol. 37, no. 22, pp. 2522-2529.
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The aim of the present study was to determine the factors affecting sports involvement in a school-based adolescent population. The cross-sectional cohort study assessed anthropometry, physical capacities and motor competence in 501 boys (aged 10-16 y), from junior (10-12 y) and senior (13-16 y) cohorts. Sports participation data was collected from junior participants. Multivariate analysis of covariance revealed moderate maturity, anthropometry, physical capacity and motor competence differences between sports in the senior cohort (F = 2.616, p < 0.001, η2 = .08), but not in the junior cohort. Furthermore, differences in physical fitness were revealed between playing levels (F = 2.616, p < 0.001, η2 = .08), with a discriminant analysis correctly classifying 73% of participants using aerobic fitness and vertical jump measures. Representative level participants engaged in more structured training and commenced organised competition at a later age (F = 4.332, p < 0.001, η2 = .21). This study's findings are twofold: 1) physical and motor competence profiles differ more between sports with increasing age, and 2) participants at a higher level of competition report delayed engagement in their main sport. As a result, schools may be the ideal environment in which to provide children and adolescents with the opportunity to sample different sports.

Luckett, T, Agar, M, DiGiacomo, M, Ferguson, C, Lam, L & Phillips, J 2019, 'Health status of people who have provided informal care or support to an adult with chronic disease in the last 5 years: results from a population-based cross-sectional survey in South Australia', Australian Health Review, vol. 43, no. 4, pp. 408-408.
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ObjectiveThe aim of the present study was to compare the health status of South Australians with recent experience of caring for an adult with chronic disease with non-carers drawn from the same population.MethodsData were collected via the South Australian Health Omnibus, an annual population-based, cross-sectional survey. Respondents were asked whether they had provided care or support in the last 5 years to someone with cancer, heart disease, respiratory disease, mental illness, neurological disease or dementia. Health status was measured using the Short Form-12 version 1 (SF-12) physical and mental component scale summary scores (PCS and MCS respectively), with poor health status defined as ≥0.5 standard deviation below the normative mean. Logistic regression explored characteristics associated with poor health status.ResultsOf 3033 respondents analysed, 987 (32.5%) reported caring experience. Poor PCS and MCS were associated with carer status, lower-than-degree-level education, employment status other than employed and annual household income less than A$60000. Being Australian born was a protective factor for PCS, whereas factors protective for MCS were being married or in a de facto relationship and age ≥65 years.ConclusionsProviding care or support in the last 5 years is independently associated with poorer health status, but not with the magnitude found in studies of current carers. Future research should explore health status recovery after completion of the caring role, and investigate whether relationships between health and socioeconomic status differ for carers versus non-carers.What is known about the topic?Population-based survey studies in Australia and overseas have consistently found that informal carers have worse health status than non-carers.What does this paper add?Including recent as well as current carers in a population-based sample was associated with less effect on health status compared with studies...

Luckett, T, Agar, M, DiGiacomo, M, Lam, L & Phillips, J 2019, 'Health status in South Australians caring for people with cancer: A population‐based study', Psycho-Oncology, vol. 28, no. 11, pp. 2149-2156.
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AbstractObjectivesTo compare physical and mental health status between cancer carers versus non‐carers in a population‐based sample and explore sociodemographic and caring characteristics associated with poor carer health status.MethodsThe South Australian Health Omnibus is a population‐based cross‐sectional survey. Carer status was self‐defined by participants as having cared for someone with cancer in the last 5 years. Health status was considered poor if it was 0.5 standard deviation lower than Australian norms on the Medical Outcomes Study 12‐Item Short‐Form (SF‐12) physical and mental component summary scores (PCS and MCS). Regression analyses compared mean PCS/MCS between carers versus non‐carers, controlling for sociodemographic variables, and explored associations between poor health status and caring and support among carers.ResultsThe weighted sample included 2962 people, of whom 374 (12.6%) were cancer carers and 1993 (67.3%) non‐carers. Carers had significantly worse PCS/MCS, controlling for sociodemographic variables, but did not differ significantly regarding proportions with poor health status. Carer characteristics associated with poor PCS and MCS included socio‐economic indicators and involvement in medication management. Assisting with household tasks was protective.ConclusionsThis population‐based study followed those previous ones in finding cancer carers to have poorer mean health status than non‐carers. However, differences were less pronounced than previously reported, likely because of the sample being drawn from a general rather than cancer service population and including past as well as current carers, as well as all cancer types and stages. Future longitudinal research is n...

Luckett, T, Davidson, PM, Green, A, Marie, N, Birch, M-R, Stubbs, J, Phillips, J, Agar, M, Boyle, F & Lovell, M 2019, 'Development of a cancer pain self-management resource to address patient, provider, and health system barriers to care', Palliative and Supportive Care, vol. 17, no. 04, pp. 472-478.
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AbstractObjectiveThe majority of self-management interventions are designed with a narrow focus on patient skills and fail to consider their potential as “catalysts” for improving care delivery. A project was undertaken to develop a patient self-management resource to support evidence-based, person-centered care for cancer pain and overcome barriers at the levels of the patient, provider, and health system.MethodThe project used a mixed-method design with concurrent triangulation, including the following: a national online survey of current practice; two systematic reviews of cancer pain needs and education; a desktop review of online patient pain diaries and other related resources; consultation with stakeholders; and interviews with patients regarding acceptability and usefulness of a draft resource.ResultFindings suggested that an optimal self-management resource should encourage pain reporting, build patients’ sense of control, and support communication with providers and coordination between services. Each of these characteristics was identified as important in overcoming established barriers to cancer pain care. A pain self-management resource was developed to include: (1) a template for setting specific, measureable, achievable, relevant and time-bound goals of care, as well as identifying potential obstacles and ways to overcome these; and (2) a pain management plan detailing exacerbating and alleviating factors, current strategies for management, and contacts for support.Significance of resultsSelf-management resources have the potential...

Luckett, T, Phillips, J, Currow, DC, Agar, M & Molassiotis, A 2019, 'Cough in lung cancer: A survey of current practice among Australian health professionals', Collegian, vol. 26, no. 6, pp. 629-633.
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© 2019 Australian College of Nursing Ltd Background: Systematic reviews and guidelines are available to guide management of cough in lung cancer, but evidence for intervention efficacy is limited, and little research has yet described current practice. Aim: To canvass the experiences and perspectives of Australian health professionals with regard to the clinical importance and current management of cough in people with lung cancer. Methods: An open, online, cross-sectional survey was conducted in 2018. Health professionals of all disciplines were eligible, and recruitment was by direct approach to lung cancer multidisciplinary teams, professional listservs and conferences. Findings: Fifty-eight people completed the survey, of whom 26 (45%) were medical practitioners, 21 (36%) registered nurses, and 10 (17%) allied health practitioners. Nearly all (>90%) considered cough to be of clinical concern and welcomed efforts to improve management. In most services, ≤25% of patients with clinically concerning cough receive management. Opiates were perceived to be the most consistently effective pharmacological strategy, with ≥50% participants indicating minimal or variable effectiveness for all others. The few participants who had experience of non-pharmacological strategies perceived these to be only somewhat or variably effective. Discussion: Results from this study identified variability in the management of cough associated with lung cancer, and suggest this problem may be under-treated in most services. Unmet needs identified by this study are likely under-estimated due to the volunteer effect associated with open surveys. Conclusion: Further efforts are needed to raise awareness about the importance of managing cough and provide evidence-based strategies for this population.

Luong, NT, Vo, TT & Hoang, D 2019, 'FAPRP: A Machine Learning Approach to Flooding Attacks Prevention Routing Protocol in Mobile Ad Hoc Networks', Wireless Communications and Mobile Computing, vol. 2019, pp. 1-17.
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Request route flooding attack is one of the main challenges in the security of Mobile Ad Hoc Networks (MANETs) as it is easy to initiate and difficult to prevent. A malicious node can launch an attack simply by sending an excessively high number of route request (RREQ) packets or useless data packets to nonexistent destinations. As a result, the network is rendered useless as all its resources are used up to serve this storm of RREQ packets and hence unable to perform its normal routing duty. Most existing research efforts on detecting such a flooding attack use the number of RREQs originated by a node per unit time as the threshold to classify an attacker. These algorithms work to some extent; however, they suffer high misdetection rate and reduce network performance. This paper proposes a new flooding attacks detection algorithm (FADA) for MANETs based on a machine learning approach. The algorithm relies on the route discovery history information of each node to capture similar characteristics and behaviors of nodes belonging to the same class to decide if a node is malicious. The paper also proposes a new flooding attacks prevention routing protocol (FAPRP) by extending the original AODV protocol and integrating FADA algorithm. The performance of the proposed solution is evaluated in terms of successful attack detection ratio, packet delivery ratio, and routing load both in normal and under RREQ attack scenarios using NS2 simulation. The simulation results show that the proposed FAPRP can detect over 99% of RREQ flooding attacks for all scenarios using route discovery frequency vector of sizes larger than 35 and performs better in terms of packet delivery ratio and routing load compared to existing solutions for RREQ flooding attacks.

Lynch, M, De Abreu Lourenco, R, Flattery, M & Haas, M 2019, 'Reviewing the cost‐effectiveness of long‐acting reversible contraceptive methods in an Australian context', Australian and New Zealand Journal of Obstetrics and Gynaecology, vol. 59, no. 1, pp. 21-35.
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BackgroundRelative to the oral contraceptive pill, uptake of long‐acting reversible contraceptive methods (LARCs) in Australia continues to be lower than might be suggested by the evidence on their clinical and economic benefits.AimTo undertake a critical appraisal of published economic evaluations of LARCs to assess the generalisability of their results to the Australian healthcare context.Materials and MethodsA search of the literature was conducted to identify studies of economic evaluations of LARCs using the Medline, Embase and PubMed databases. The quality of the studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.ResultsA total of 1009 citations were screened, from which 20 papers, typically reporting the cost per pregnancy avoided, were reviewed. The overall quality of the studies varied but was generally poor (average score of 62/100). To aid comparisons, results have been grouped under the headings IUS (all hormonal intrauterine systems), IUDs (all non‐hormonal intrauterine devices), injectables (all contraceptive injections) and implants (all subdermal contraceptive implants). Overall, the results indicated that LARCs were more effective and less costly than oral contraceptives.Conclusions<...

Macha, IJ, Ben-Nissan, B, Vilchevskaya, EN, Morozova, AS, Abali, BE, Müller, WH & Rickert, W 2019, 'Drug Delivery From Polymer-Based Nanopharmaceuticals—An Experimental Study Complemented by Simulations of Selected Diffusion Processes', Frontiers in Bioengineering and Biotechnology, vol. 7.
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The success of medical therapy depends on the correct amount and the appropriate delivery of the required drugs for treatment. By using biodegradable polymers a drug delivery over a time span of weeks or even months is made possible. This opens up a variety of strategies for better medication. The drug is embedded in a biodegradable polymer (the "carrier") and injected in a particular position of the human body. As a consequence of the interplay between the diffusion process and the degrading polymer the drug is released in a controlled manner. In this work we study the controlled release of medication experimentally by measuring the delivered amount of drug within a cylindrical shell over a long time interval into the body fluid. Moreover, a simple continuum model of the Fickean type is initially proposed and solved in closed-form. It is used for simulating some of the observed release processes for this type of carrier and takes the geometry of the drug container explicitly into account. By comparing the measurement data and the model predictions diffusion coefficients are obtained. It turns out that within this simple model the coefficients change over time. This contradicts the idea that diffusion coefficients are constants independent of the considered geometry. The model is therefore extended by taking an additional absorption term into account leading to a concentration dependent diffusion coefficient. This could now be used for further predictions of drug release in carriers of different shape. For a better understanding of the complex diffusion and degradation phenomena the underlying physics is discussed in detail and even more sophisticated models involving different degradation and mass transport phenomena are proposed for future work and study.

Macha, IJ, Karacan, I, Ben-Nissan, B, Cazalbou, S & Müller, WH 2019, 'Development of antimicrobial composite coatings for drug release in dental, orthopaedic and neural prostheses applications', SN Applied Sciences, vol. 1, no. 1.
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While one of the major clinical and scientific challenges in the management of implant-related infections and post-operative complications after surgery is the application of new techniques, a new approach is pertinent in the design of medical implants to reduce bacterial infections. We have designed and tested antibiotic-containing biocomposite thin films of polylactic acid (PLA), and coralline-derived hydroxyapatite (HAp) as controlled drug delivery systems for the treatment of dental, orthopaedic and neural implant-related post-operative infections. These films can be applied to complicated designs of dental, miniaturized neural devices, cochlear or total hip replacement (THR) implants by spray or dip-coating techniques. Current results reveal that the devices could release antibiotic in a controlled manner to prevent significantly bacterial growth and biofilm production. Hydroxyapatite within the composites controls the release rate and also supplies minerals, such as calcium Ca2+ and phosphate PO42− ions, which are essential minerals for bone tissue regeneration. It is concluded from the physical, mechanical and biological properties that these coatings and devices could easily be utilized in a wide range of biomedical applications.

Machaalani, R, Thawley, M, Huang, J & Chen, H 2019, 'Effects of prenatal cigarette smoke exposure on BDNF, PACAP, microglia and gliosis expression in the young male mouse brainstem', NeuroToxicology, vol. 74, pp. 40-46.
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© 2019 Elsevier B.V. Cigarette smoke exposure during pregnancy into infancy affects brain growth and development in both short and long term (into adulthood). Using a mouse model of pre- into post- natal cigarette smoke exposure (SE), we aimed to determine the effects on brain derived neurotrophic factor (BDNF) and its receptor TrkB, neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor PAC1, and astrocyte (GFAP) and microglia (Iba-1) immunohistochemical expression, in seven nuclei of the medulla and the facial (FAC) nucleus of the pons. Male pups of dams exposed to two cigarettes (nicotine <1.2 mg, CO <15 mg) twice daily for six weeks prior to mating, during gestation and lactation (n = 5; SE), were compared to pups exposed to air under the same condition (n = 5; SHAM) at postnatal day 20. Expression changes were only evident for BDNF, TrkB and PAC1 and included decreased BDNF in the hypoglossal (XII) nucleus and nucleus of the solitary tract (NTS), increased TrkB in XII but decreased TrkB in the FAC, and increased PAC1 in 4 nuclei of the medulla including the NTS. These results suggest that the effect of SE on the brainstem are region and marker selective, affecting regions of respiratory control (XII and NTS), and restricted to the BDNF system and PAC1, with no effect on activation states of astrocytes or microglia.

MacManus, M, De Abreu Lourenco, R & Hegi-Johnson, F 2019, 'Helping patients with lung cancer choose between surgery or stereotactic body radiotherapy: the importance of the patient experience', Journal of Thoracic Disease, vol. 11, no. 11, pp. 4404-4407.
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Mahmoodi, Z, Mohammadnejad, J, Razavi Bazaz, S, Abouei Mehrizi, A, Ghiass, MA, Saidijam, M, Dinarvand, R, Ebrahimi Warkiani, M & Soleimani, M 2019, 'A simple coating method of PDMS microchip with PTFE for synthesis of dexamethasone-encapsulated PLGA nanoparticles', Drug Delivery and Translational Research, vol. 9, no. 3, pp. 707-720.
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© 2019, Controlled Release Society. Dexamethasone is a widely used drug in medical and biological applications. Since the systematic and controllable release of this drug is of significant importance, encapsulation of this anti-inflammatory drug in poly(lactic-co-glycolic acid) (PLGA) nanoparticles can minimize uncontrolled issues. As dexamethasone-encapsulated PLGA nanoparticles are synthesized in the presence of organic solvents, poly(dimethylsiloxane) (PDMS)-based microchannels collapse due to the swelling problem. In present study, PTFE nanoparticles were used for the surface modification of the microchannels to prevent absorption and adhesion of solvents into the microchannels’ wall. The contact angle analysis of microchips after coating showed that the surface of microchannels bear the superhydrophobicity feature (140.30°) and SEM images revealed that PTFE covered the surface of PDMS, favorably. Then, the prepared microchip was tested for the synthesis of dexamethasone-loaded nanoparticles. SEM and atomic force microscopy (AFM) images of the synthesized nanoparticles represented that there was not any evidence of adhesion or absorption of nanoparticles. Furthermore, the monodispersity of nanoparticles was discernible. As AFM results revealed, the average diameters of 47, 63, and 82 nm were achieved for flow ratios of 0.01, 0.05, and 0.1, respectively. To evaluate the drug efficiency, cumulative release and encapsulation efficiency were analyzed which showed much more efficiency than the synthesized nanoparticles in the bulk mode. In addition, MTT test revealed that nanoparticles could be considered as a non-toxic material. Since the synthesis of drug-loaded nanoparticles is ubiquitous in laboratory experiments, the approach presented in this study can render more versatility in this regard.

Mai, HT, Tran, TS, Ho-Le, TP, Center, JR, Eisman, JA & Nguyen, TV 2019, 'Response to Letter to the Editor: “Two-Thirds of All Fractures Are Not Attributable to Osteoporosis and Advancing Age: Implication for Fracture Prevention”', The Journal of Clinical Endocrinology & Metabolism, vol. 104, no. 9, pp. 3605-3606.
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Mai, HT, Tran, TS, Ho-Le, TP, Center, JR, Eisman, JA & Nguyen, TV 2019, 'Response to Letter to the Editor: “Two-Thirds of All Fractures Are Not Attributable to Osteoporosis and Advancing Age: Implications for Fracture Prevention”', The Journal of Clinical Endocrinology & Metabolism, vol. 104, no. 12, pp. 5866-5866.
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Marsh-Wakefield, F, Kruzins, A, McGuire, HM, Yang, S, Bryant, C, Fazekas de St. Groth, B, Nassif, N, Byrne, SN, Gibson, J, Brown, C, Larsen, S, McCulloch, D, Boyle, R, Clark, G, Joshua, D, Ho, PJ & Vuckovic, S 2019, 'Mass Cytometry Discovers Two Discrete Subsets of CD39−Treg Which Discriminate MGUS From Multiple Myeloma', Frontiers in Immunology, vol. 10, no. AUG, p. 1596.
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© 2019 Marsh-Wakefield, Kruzins, McGuire, Yang, Bryant, Fazekas de St. Groth, Nassif, Byrne, Gibson, Brown, Larsen, McCulloch, Boyle, Clark, Joshua, Ho and Vuckovic. Multiple Myeloma (MM) is preceded by the clinically stable condition monoclonal gammopathy of undetermined significance (MGUS). Critical immune events that discriminate MGUS from newly diagnosed MM (ND)MM patients remain unknown, but may involve changes in the regulatory T cell (Treg) compartment that favor myeloma growth. To address this possibility, we used mass cytometry and the unsupervised clustering algorithm Flow self-organizing map (FlowSOM) to interrogate the distribution of multiple subsets within CD25+ CD127low/neg Treg in matched bone marrow (BM) and peripheral blood (PB) of MGUS and NDMM patients. Both mass cytometry and flow cytometry confirmed a trend toward prevalence of CD39− Treg within the Treg compartment in BM and PB of NDMM patients compared to CD39− Treg in MGUS patients. FlowSOM clustering displayed a phenotypic organization of Treg into 25 metaclusters that confirmed Treg heterogeneity. It identified two subsets which emerged within CD39− Treg of NDMM patients that were negligible or absent in CD39− Treg of MGUS patients. One subset was found in both BM and PB which phenotypically resembled activated Treg based on CD45RO, CD49d, and CD62L expression; another subset resembled BM-resident Treg based on its tissue-resident CD69+ CD62L− CD49d− phenotype and restricted location within the BM. Both subsets co-expressed PD-1 and TIGIT, but PD-1 was expressed at higher levels on BM-resident Treg than on activated Treg. Within BM, both subsets had limited Perforin and Granzyme B production, whilst activated Treg in PB acquired high Perforin and Granzyme B production. In conclusion, the use of mass cytometry and FlowSOM clustering discovered two discrete subsets of CD39− Treg which are discordant in MGUS and NDMM patients and may be permissive of myeloma growth which warrants...

Martin Salvador, M, Budka, M & Gabrys, B 2019, 'Automatic Composition and Optimization of Multicomponent Predictive Systems With an Extended Auto-WEKA', IEEE Transactions on Automation Science and Engineering, vol. 16, no. 2, pp. 946-959.
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© 2004-2012 IEEE. Composition and parameterization of multicomponent predictive systems (MCPSs) consisting of chains of data transformation steps are a challenging task. Auto-WEKA is a tool to automate the combined algorithm selection and hyperparameter (CASH) optimization problem. In this paper, we extend the CASH problem and Auto-WEKA to support the MCPS, including preprocessing steps for both classification and regression tasks. We define the optimization problem in which the search space consists of suitably parameterized Petri nets forming the sought MCPS solutions. In the experimental analysis, we focus on examining the impact of considerably extending the search space (from approximately 22000 to 812 billion possible combinations of methods and categorical hyperparameters). In a range of extensive experiments, three different optimization strategies are used to automatically compose MCPSs for 21 publicly available data sets. The diversity of the composed MCPSs found is an indication that fully and automatically exploiting different combinations of data cleaning and preprocessing techniques is possible and highly beneficial for different predictive models. We also present the results on seven data sets from real chemical production processes. Our findings can have a major impact on the development of high-quality predictive models as well as their maintenance and scalability aspects needed in modern applications and deployment scenarios. Note to Practitioners - The extension of Auto-WEKA to compose and optimize multicomponent predictive systems (MCPSs) developed as part of this paper is freely available on GitHub under GPL license, and we encourage practitioners to use it on a broad variety of classification and regression problems. The software can either be used as a blackbox - where search space is made of all possible WEKA filters, predictors, and metapredictors (e.g., ensembles) - or as an optimization tool on a subset of preselected machine ...

McAlinden, KD, Deshpande, DA, Ghavami, S, Xenaki, D, Sohal, SS, Oliver, BG, Haghi, M & Sharma, P 2019, 'Autophagy Activation in Asthma Airways Remodeling', American Journal of Respiratory Cell and Molecular Biology, vol. 60, no. 5, pp. 541-553.
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Copyright © 2019 by the American Thoracic Society Current asthma therapies fail to target airway remodeling that correlates with asthma severity driving disease progression that ultimately leads to loss of lung function. Macroautophagy (hereinafter “autophagy”) is a fundamental cell-recycling mechanism in all eukaryotic cells; emerging evidence suggests that it is dysregulated in asthma. We investigated the interrelationship between autophagy and airway remodeling and assessed preclinical efficacy of a known autophagy inhibitor in murine models of asthma. Human asthmatic and nonasthmatic lung tissues were histologically evaluated and were immunostained for key autophagy markers. The percentage area of positive staining was quantified in the epithelium and airway smooth muscle bundles using ImageJ software. Furthermore, the autophagy inhibitor chloroquine was tested intranasally in prophylactic (3 wk) and treatment (5 wk) models of allergic asthma in mice. Human asthmatic tissues showed greater tissue inflammation and demonstrated hallmark features of airway remodeling, displaying thickened epithelium (P, 0.001) and reticular basement membrane (P, 0.0001), greater lamina propria depth (P, 0.005), and increased airway smooth muscle bundles (P, 0.001) with higher expression of Beclin-1 (P, 0.01) and ATG5 (autophagy-related gene 5) (P, 0.05) together with reduced p62 (P, 0.05) compared with nonasthmatic control tissues. Beclin-1 expression was significantly higher in asthmatic epithelium and ciliated cells (P, 0.05), suggesting a potential role of ciliophagy in asthma. Murine asthma models demonstrated effective preclinical efficacy (reduced key features of allergic asthma: airway inflammation, airway hyperresponsiveness, and airway remodeling) of the autophagy inhibitor chloroquine. Our data demonstrate cell context–dependent and selective activation of autophagy in structural cells in asthma. Furthermore, this pathway can be effectively targeted to amelio...

McCleave, EL, Slattery, KM, Duffield, R, Saunders, PU, Sharma, AP, Crowcroft, S & Coutts, AJ 2019, 'Impaired Heat Adaptation From Combined Heat Training and “Live High, Train Low” Hypoxia', International Journal of Sports Physiology and Performance, vol. 14, no. 5, pp. 635-643.
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Purpose: To determine whether combining training in heat with “Live High, Train Low” hypoxia (LHTL) further improves thermoregulatory and cardiovascular responses to a heat-tolerance test compared with independent heat training. Methods: A total of 25 trained runners (peak oxygen uptake = 64.1 [8.0] mL·min−1·kg−1) completed 3-wk training in 1 of 3 conditions: (1) heat training combined with “LHTL” hypoxia (H+H; FiO2 = 14.4% [3000 m], 13 h·d−1; train at <600 m, 33°C, 55% relative humidity [RH]), (2) heat training (HOT; live and train <600 m, 33°C, 55% RH), and (3) temperate training (CONT; live and train <600 m, 13°C, 55% RH). Heat adaptations were determined from a 45-min heat-response test (33°C, 55% RH, 65% velocity corresponding to the peak oxygen uptake) at baseline and immediately and 1 and 3 wk postexposure (baseline, post, 1 wkP, and 3 wkP, respectively). Core temperature, heart rate, sweat rate, sodium concentration, plasma volume, and perceptual responses were analyzed using magnitude-based inferences. Results: Submaximal heart rate (effect size [ES] = −0.60 [−0.89; −0.32]) and core temperature (ES = −0.55 [−0.99; −0.10]) were reduced in HOT until 1 wkP. Sweat rate (ES = 0.36 [0.12; 0.59]) and sweat sodium concentration (ES = −0.82 [−1.48; −0.16]) were, respectively, increased and decreased until 3 wkP in HOT. Submaximal heart rate (ES = −0.38 [−0.85; 0.08]) was likely reduced in H+H at 3 wkP, whereas CONT had unclear physiological changes. Perceived exertion and thermal sensation were reduced across all groups. Conclusions: Despite greater physiological stress from combined heat training and “LHTL” hypoxia, thermoregulatory ada...

McLean, BD, Strack, D, Russell, J & Coutts, AJ 2019, 'Quantifying Physical Demands in the National Basketball Association—Challenges Around Developing Best-Practice Models for Athlete Care and Performance', International Journal of Sports Physiology and Performance, vol. 14, no. 4, pp. 414-420.
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The National Basketball Association (NBA) has an extremely demanding competition schedule, requiring its athletes to compete in 82 regular-season games over a 6-mo period (∼3.4 games/wk). Despite the demanding schedule and high value of athletes, there is little public information on the specific game and training demands required to compete in the NBA. Although provisions in the NBA collective-bargaining agreement allow for research designed to improve player health and broaden medical knowledge, such information is sparse in the available literature. In relation to the physical demands of the NBA, the current lack of information likely results from multiple factors including limited understanding of (basketball-related) emerging technologies, impact of specific league rules, and steps taken to protect players in the age of Big Data. This article explores current limitations in describing specific game/training demands in the NBA and provides perspectives on how some of these challenges may be overcome. The authors propose that future collaborations between league entities, NBA clubs, commercial partners, and outside research institutions will enhance understanding of the physical demands in the NBA (and other health- and performance-related areas). More detailed understanding of physical demands (games, practices, and travel) and other health-related areas can augment player-centered decision making, leading to enhanced player care, increased availability, and improved physical performance.

Meller, N, Parker, D, Hatcher, D & Sheehan, A 2019, 'Grief experiences of nurses after the death of an adult patient in an acute hospital setting: An integrative review of literature', Collegian, vol. 26, no. 2, pp. 302-310.
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© 2018 Australian College of Nursing Ltd Objective: This integrative review explores current published literature examining grief experiences of nurses who work in hospital settings after the death of a patient in their care and the factors that may impact nurses experiencing grief within the workplace. Background: Healthcare workers such as nurses are required to be competent, skilled and resilient in preparation for the emotional variables and professional responsibilities when managing a patient death. There are publications exploring nurse's grief experiences in palliative care, paediatric nursing or oncology settings, but to date, there is limited relevant literature identifying or exploring grief experiences of nurses working in other speciality areas in a hospital setting after the death of a patient in their care. Methods: Comprehensive online database searches of CINAHL, EBSCO Host, PubMED, MEDLINE, Scopus, Joanna Briggs Institute (JBI) and Google Scholar was undertaken using key terms of articles published between 1990–2017. Screening of 317 articles resulted in 5 included for this review. Data analysis was guided by Whittemore and Knafl's five stage process. Findings: Three main themes were identified were ‘the impact of formative death events in clinical practice’ ‘managing personal grief reactions and the factors that influenced these reactions’ and ‘the significance of colleague support when experiencing a patient death’. Conclusion: Personal grief responses displayed by a nurse after a patient has died can have both a positive and negative influence on their professional behaviour in the workplace. It also has the potential for grief complications for individual nurses, which highlights the importance of workplace support for nurses when making clinical decisions after the death of a patient.

Miller-Lewis, L, Tieman, J, Rawlings, D, Sanderson, C & Parker, D 2019, 'Correlates of perceived death competence: What role does meaning-in-life and quality-of-life play?', Palliative and Supportive Care, vol. 17, no. 5, pp. 550-560.
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AbstractObjectiveUnderstanding factors that are associated with more adaptive death attitudes and competencies can inspire future health-promoting palliative care strategies and inform approaches to training and development for health professionals. The potential importance of meaning, purpose, quality, and values in life for promoting adaptive death attitudes has been highlighted, but there is limited research in this area, particularly in relation to death competence. The purpose of this cross-sectional study was to develop an understanding of demographic and life-related factors associated with perceived death competence, such as meaning in life and quality of life.MethodDuring the course enrollment period of a Massive-Online-Open-Course about death and dying, 277 participants completed questionnaires on death competence, meaning in life, quality of life, and sociodemographic background.ResultFindings indicated that greater presence of meaning in life, quality of life, age, death experience, and carer experience were each statistically significant unique predictors of death competence scores. Life-related variables were more strongly associated with death competence than demographic variables. Bereavement experience and experience caring for the dying was associated with greater death competence, but there were no differences on death competence between health professionals and the general community. Above all other factors, the presence of meaning in life was the strongest predictor of higher perceived competence in coping with death.Significance of results

Mofradnia, SR, Ashouri, R, Tavakoli, Z, Shahmoradi, F, Rashedi, H, Yazdian, F & Tavakoli, J 2019, 'Effect of zero-valent iron/starch nanoparticle on nitrate removal using MD simulation', International Journal of Biological Macromolecules, vol. 121, pp. 727-733.
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In this study, the efficacy of zero-valent iron nanostructure modified by starch for removal of nitrate was investigated. Effect of zero-valent iron/starch nanoparticle in the presence of Thiobacillus dinitrificans for removal of nitrate was simulated via material studio software. Thermodynamic principles and proper equations were used via molecular dynamic (MD) simulation. The results of software predictions were demonstrated by radial distribution function (RDF), density, potential energy and temperature graphs. According to the graphs, the simultaneous in the presence of zero-valent iron/starch nanoparticle and Thiobacillus dinitrificans increase the removal efficiency of nitrate reached 91% and in the absence of nanoparticle was 44.44%.

Moloudi, R, Oh, S, Yang, C, Teo, KL, Lam, AT, Ebrahimi Warkiani, M & Win Naing, M 2019, 'Scaled‐Up Inertial Microfluidics: Retention System for Microcarrier‐Based Suspension Cultures', Biotechnology Journal, vol. 14, no. 5, pp. 1800674-1800674.
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Recently, particle concentration and filtration using inertial microfluidics have drawn attention as an alternative to membrane and centrifugal technologies for industrial applications, where the target particle size varies between 1 µm and 500 µm. Inevitably, the bigger particle size (>50 µm) mandates scaling up the channel cross‐section or hydraulic diameter (DH > 0.5 mm). The Dean‐coupled inertial focusing dynamics in spiral microchannels is studied broadly; however, the impacts of secondary flow on particle migration in a scaled‐up spiral channel is not fully elucidated. The mechanism of particle focusing inside scaled‐up rectangular and trapezoidal spiral channels (i.e., 5–10× bigger than conventional microchannels) with an aim to develop a continuous and clog‐free microfiltration system for bioprocessing is studied in detail. Herein, a unique focusing based on inflection point without the aid of sheath flow is reported. This new focusing mechanism, observed in the scaled‐up channels, out‐performs the conventional focusing scenarios in the previously reported trapezoidal and rectangular channels. Finally, as a proof‐of‐concept, the utility of this device is showcased for the first time as a retention system for a cell–microcarrier (MC) suspension culture.

Moodley, YP, Corte, TJ, Oliver, BG, Glaspole, IN, Livk, A, Ito, J, Peters, K, Lipscombe, R, Casey, T & Tan, DBA 2019, 'Analysis by proteomics reveals unique circulatory proteins in idiopathic pulmonary fibrosis', Respirology, vol. 24, no. 11, pp. 1111-1114.
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ABSTRACTBackground and objectiveIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease that has a poor 3‐year median survival rate with unclear pathophysiology. Radiological features include bibasal, subpleural fibrosis and honeycombing while its pathology is characterized by fibroblastic foci and honeycombing. Proteomic analysis of circulating molecules in plasma may identify factors that characterize IPF and may assist in the diagnosis, prognostication and determination of pathogenic pathways in this condition.MethodsTwo independent quantitative proteomic techniques were used, isobaric tags for relative and absolute quantitation (iTRAQ) and multiple reaction monitoring (MRM), to identify differentially expressed plasma proteins in a group of IPF patients in comparison to healthy controls with normal lung function matched for age and gender.ResultsFive proteins were identified to be differentially expressed in IPF compared to healthy controls (upregulation of platelet basic protein and downregulation of actin, cytoplasmic 2, antithrombin‐III, extracellular matrix protein‐1 and fibronectin).ConclusionThis study further validates the combinational use of non‐targeted discovery proteomics (iTRAQ) with targeted quantitation by mass spectrometry (MRM) of soluble biomarkers to identify potentially important molecules and pathways for pulmonary diseases such as IPF.

Movassaghi, S, Nadia Sharifi, Z, Koosha, M, Abdollahifar, MA, Fathollahipour, S, Tavakoli, J & Abdi, S 2019, 'Effect of Honey/PVA Hydrogel Loaded by Erythromycin on Full-Thickness Skin Wound Healing in Rats; Stereological Study.', Galen Med J, vol. 8, p. e1362.
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BACKGROUND: Skin wounds are a significant public health risk, and treatment of wound remains a challenging clinical problem for medical teams and researchers. MATERIALS AND METHODS: In the present study, we aimed to investigate the healing effects of honey/polyvinyl alcohol (PVA) hydrogel loaded with erythromycin as wound dressing on skin wounds in rats, based on histological studies. In this study, 60 male Wistar rats, with a 1.5 ×1.5 cm2 diameter full-thickness wounds on the backs were divided into four groups: honey/PVA with the erythromycin hydrogel group, honey group, PVA group, and the control group, with no treatment. Skin biopsies were prepared at days 4, 7, and 14 for microscopic analyses. The stereological analysis, including the mean area of the wound, length of vessels, numerical density of fibroblast, macrophage, basal cell and volume of the epidermis, dermis, and fibrous tissue were performed. RESULTS: Wounds area in the honey/PVA hydrogel with the erythromycin group were significantly (P<0.05) smaller than in the other group. The numerical density of fibroblast, macrophage, basal cell and volume of the epidermis in the honey/PVA hydrogel with the erythromycin group were significantly higher than other groups. CONCLUSION: According to our results, honey/PVA hydrogel with erythromycin may promote early wound healing and has a positive influence on fibroblast proliferation and re-epithelialization, and its administration is recommended after further validation of clinical data.

Mulhern, B, Norman, R, De Abreu Lourenco, R, Street, D, Malley, J & Viney, R 2019, 'Investigating the relative value of health and social care related quality of life using a discrete choice experiment', Social Science and Medicine, vol. 233, pp. 28-37.
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Nader, CP, Cidem, A, Verrills, NM & Ammit, AJ 2019, 'Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer', Respiratory Research, vol. 20, no. 1, p. 222.
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AbstractLung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked than once thought. Emerging data in relation to a key phosphatase, protein phosphatase 2A (PP2A), and its regulatory role in inflammatory and tumour suppression in both disease settings suggests that it may be critical in the progression of COPD to LC. In this review, we uncover the importance of the functional and active PP2A holoenzyme in the context of both diseases. We describe PP2A inactivation via direct and indirect means and explore the actions of two key PP2A endogenous inhibitors, cancerous inhibitor of PP2A (CIP2A) and inhibitor 2 of PP2A (SET), and the role they play in COPD and LC. We explain how dysregulation of PP2A in COPD creates a favourable inflammatory micro-environment and promotes the initiation and progression of tumour pathogenesis. Finally, we highlight PP2A as a druggable target in the treatment of COPD and LC and demonstrate the potential of PP2A re-activation as a strategy to halt COPD disease progression to LC. Although further studies are required to elucidate if PP2A activity in COPD is a causal link for LC progression, studies focused on the potential of PP2A reactivating agents to reduce the risk of LC formation in COPD patients will be pivotal in improving clinical outcomes for both COPD and LC patients in the future.

Nair, PM, Starkey, MR, Haw, TJ, Liu, G, Collison, AM, Mattes, J, Wark, PA, Morris, JC, Verrills, NM, Clark, AR, Ammit, AJ & Hansbro, PM 2019, 'Enhancing tristetraprolin activity reduces the severity of cigarette smoke‐induced experimental chronic obstructive pulmonary disease', Clinical & Translational Immunology, vol. 8, no. 10.
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AbstractObjectiveChronic obstructive pulmonary disease (COPD) is a progressive disease that causes significant mortality and morbidity worldwide and is primarily caused by the inhalation of cigarette smoke (CS). Lack of effective treatments for COPD means there is an urgent need to identify new therapeutic strategies for the underlying mechanisms of pathogenesis. Tristetraprolin (TTP) encoded by the Zfp36 gene is an anti‐inflammatory protein that induces mRNA decay, especially of transcripts encoding inflammatory cytokines, including those implicated in COPD.MethodsHere, we identify a novel protective role for TTP in CS‐induced experimental COPD using Zfp36aa/aa mice, a genetically modified mouse strain in which endogenous TTP cannot be phosphorylated, rendering it constitutively active as an mRNA‐destabilising factor. TTP wild‐type (Zfp36+/+) and Zfp36aa/aa active C57BL/6J mice were exposed to CS for four days or eight weeks, and the impact on acute inflammatory responses or chronic features of COPD, respectively, was assessed.ResultsAfter four days of CS exposure, Zfp36aa/aa mice had reduced numbers of airway neutrophils and lymphocytes and mRNA expression levels of cytokines compared to wild‐type controls. After eight weeks, Zfp36aa/aa mice had reduced pulmonary inflammation, airway remodelling and emphysema‐like alveolar enlargement, and lung function was improved. We then used pharmacological treatments in vivo (protein phosphatase 2A activator, AAL(S)

Natalia, P, Clara, RA, Simon, D, Noelia, G & Barbara, A 2019, 'Critical elements in accessible tourism for destination competitiveness and comparison: Principal component analysis from Oceania and South America', Tourism Management, vol. 75, pp. 169-185.
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© 2019 This paper seeks to construct an exploratory nationally comparative tourism accessibility measure (TAI)through developing an objective set of metrics in the spirit and intent of the international treaties and missions regarding the rights of persons with disabilities. Applied to Australia and New Zealand (Oceania)and Argentina and Brazil (South-America), the TAI draws upon data collected cross-country, cross-continent and for a period of 25 years (1990–2015)based on factor and principal component analysis. Considering accessibility as the conditions that a destination must have in order to be enjoyed by all individuals with access requirements and as a key factor of destination competitiveness, the TAI is developed based on: socio-demographic data; legal framework, political will and policy actions; and access conditions in tourism attractions. This measure is a useful tool to provide information about the critical elements, stages of development, evolution and understanding of the accessible tourism approaches in each of the studied countries.

Naylor, B, Hesam-Shariati, N, McAuley, JH, Boag, S, Newton-John, T, Rae, CD & Gustin, SM 2019, 'Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain', Frontiers in Neurology, vol. 10.
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A decrease in glutamate in the medial prefrontal cortex (mPFC) has been extensively found in animal models of chronic pain. Given that the mPFC is implicated in emotional appraisal, cognition and extinction of fear, could a potential decrease in glutamate be associated with increased pessimistic thinking, fear and worry symptoms commonly found in people with chronic pain? To clarify this question, 19 chronic pain subjects and 19 age- and gender-matched control subjects without pain underwent magnetic resonance spectroscopy. Both groups also completed the Temperament and Character, the Beck Depression and the State Anxiety Inventories to measure levels of harm avoidance, depression, and anxiety, respectively. People with chronic pain had significantly higher scores in harm avoidance, depression and anxiety compared to control subjects without pain. High levels of harm avoidance are characterized by excessive worry, pessimism, fear, doubt and fatigue. Individuals with chronic pain showed a significant decrease in mPFC glutamate levels compared to control subjects without pain. In people with chronic pain mPFC glutamate levels were significantly negatively correlated with harm avoidance scores. This means that the lower the concentration of glutamate in the mPFC, the greater the total scores of harm avoidance. High scores are associated with fearfulness, pessimism, and fatigue-proneness. We suggest that chronic pain, particularly the stress-induced release of glucocorticoids, induces changes in glutamate transmission in the mPFC, thereby influencing cognitive, and emotional processing. Thus, in people with chronic pain, regulation of fear, worry, negative thinking and fatigue is impaired.

Ng, SW, Chan, Y, Chellappan, DK, Madheswaran, T, Zeeshan, F, Chan, YL, Collet, T, Gupta, G, Oliver, BG, Wark, P, Hansbro, N, Hsu, A, Hansbro, PM, Dua, K & Panneerselvam, J 2019, 'Molecular modulators of celastrol as the keystones for its diverse pharmacological activities', Biomedicine & Pharmacotherapy, vol. 109, pp. 1785-1792.
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© 2018 The Authors In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.

Nguyen, L, Mak, C, Chen, H, Zaky, A, Wong, M, Pollock, C & Saad, S 2019, 'SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet', Nutrients, vol. 11, no. 1, pp. 146-146.
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Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury.

Nguyen, L, Valls Miro, J & Qiu, X 2019, 'Multilevel B-Splines-Based Learning Approach for Sound Source Localization', IEEE Sensors Journal, vol. 19, no. 10, pp. 3871-3881.
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© 2001-2012 IEEE. In this paper, a new learning approach for sound source localization is presented using ad hoc either synchronous or asynchronous distributed microphone networks based on the time differences of arrival (TDOA) estimation. It is first to propose a new concept in which the coordinates of a sound source location are defined as the functions of TDOAs, computing for each pair of microphone signals in the network. Then, given a set of pre-recorded sound measurements and their corresponding source locations, the multilevel B-splines-based learning model is proposed to be trained by the input of the known TDOAs and the output of the known coordinates of the sound source locations. For a new acoustic source, if its sound signals are recorded, the correspondingly computed TDOAs can be fed into the learned model to predict the location of the new source. Superiorities of the proposed method are to incorporate the acoustic characteristics of a targeted environment and even remaining uncertainty of TDOA estimations into the learning model before conducting its prediction and to be applicable for both synchronous or asynchronous distributed microphone sensor networks. The effectiveness of the proposed algorithm in terms of localization accuracy and computational cost in comparisons with the state-of-the-art methods was extensively validated on both synthetic simulation experiments as well as in three real-life environments.

Nguyen, LT, Chen, H, Zaky, A, Pollock, C & Saad, S 2019, 'SIRT1 overexpression attenuates offspring metabolic and liver disorders as a result of maternal high‐fat feeding', The Journal of Physiology, vol. 597, no. 2, pp. 467-480.
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Key pointsMaternal high‐fat diet (MHF) consumption led to metabolic and liver disorders in male offspring, which are associated with reduced sirtuin (SIRT)1 expression and activity in the offspring liverSIRT1 overexpression in MHF offspring reduced their body weight and adiposity and normalized lipid metabolic markers in epididymal and retroperitoneal adipose tissuesSIRT1 overexpression in MHF offspring improved glucose tolerance, as well as systemic and hepatic insulin sensitivitySIRT1 overexpression ameliorated MHF‐induced lipogenesis, oxidative stress and fibrogenesis in the liver of offspring.AbstractMaternal obesity can increase the risk of metabolic disorders in the offspring. However, the underlying mechanism responsible for this is not clearly understood. Previous evidence implied that sirtuin (SIRT)1, a potent regulator of energy metabolism and stress responses, may play an important role. In the present study, we have shown, in C57BL/6 mice, that maternal high‐fat diet (HFD) consumption can induce a pre‐diabetic and non‐alcoholic fatty liver disease phenotype in the offspring, associated with reduced SIRT1 expression in the hypothalamus, white adipose tissues (WAT) and liver. Importantly, the overexpression of SIRT1 in these offspring significantly attenuated the excessive accumulation of epididymal (Epi) white adipose tissue (WAT) and retroperitoneal (Rp)WAT (P < 0.001), glucose intolerance and insulin resistance (both P < 0.05) at weaning age. These changes were associated with the suppression of peroxisome proliferator‐activated recept...

Nguyen, LT, Pham, VN, Chau, PMN, Ho-Pham, LT & Nguyen, TV 2019, 'Association between carotid intima-media thickness and bone mineral density: a cross-sectional study in Vietnamese men and women aged 50 years and older', BMJ Open, vol. 9, no. 9, pp. e028603-e028603.
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ObjectivesThe association between osteoporosis and atherosclerosis remains controversial. We sought to define the relationship between carotid intima-media thickness and bone mineral density (BMD) in individuals of Vietnamese background.Design and settingCross-sectional study in Ho Chi Minh City, Vietnam.ParticipantsThe study involved 1460 individuals (559 men) aged 50 years and older (average age 59 years) who were randomly recruited from the community.Outcome measuresBMD at the femoral neck and lumbar spine was measured by dual-energy X-ray absorptiometry (Hologic, Waltham, Massachusetts, USA). Carotid intima-media thickness (cIMT) was measured using a Philips Ultrasonography (HD7XE). The presence of atherosclerotic plaque was ascertained for each individual. The association between cIMT and BMD was analysed by a multiple linear regression model.ResultsIn unadjusted analysis, cIMT was positively associated with femoral neck BMD in men (p=0.005), but not in women (p=0.242). After adjusting for age, smoking, diabetes and hypertension, the association remained statistically significant in men (partial R2=0.005; p=0.015) but not in women (partial R2=0.008; p=0.369). When the analysis was limited to individuals aged 60 years and older, the association between cIMT and BMD was no longer statistically significant. There was no statistically significant association between cIMT and lumbar spine BMD in either men or women.ConclusionsIn Vietnamese individuals aged 50 years and older, there is a clinically non-significant but statistically significant association betwee...

Nguyen, LTN, Eager, D & Nguyen, H 2019, 'The relationship between compression garments and electrocardiogram signals during exercise and recovery phase', BioMedical Engineering OnLine, vol. 18, no. 1, pp. 27-27.
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© 2019 The Author(s). Background: The direction of the current research was to investigate whether electrocardiogram (ECG) signals have been impacted by using compression garments during exercise and recovery phase. Each subject is non-athletes, conducted two running tests, wearing either non-compression garments (NCGs) or compression garments (CGs) throughout experiments and 2-h of the recovery phase. Experiment 1 (number of participants (n) = 8; 61.4 ± 13.7 kg, 25.1 ± 3.8 years, 165.9 ± 8.3 cm) focused on the exercising phase while Experiment 2 (n = 14; 60.9 ± 12.0 kg, 24.7 ± 4.5 years, 166.0 ± 7.6 cm) concentrated on the recovery phase. Electrocardiogram (ECG) data were collected through wearable biosensors. Results: The results demonstrated a significant difference between compression garments and non-compression garments at the end of the tests and from 90 min onwards during the recovery phase (p < 0.05). Corrected QT (QTc), ST interval and heart rate (HR) indicated the significant difference between NCGs and CGs. Conclusion: Based on the findings, the utilization of compression garments showed a positive influence in non-athletes based on the quicker recovery in HR, ST, and QTc.

Nguyen, T, Li, GE, Chen, H, Cranfield, CG, McGrath, KC & Gorrie, CA 2019, 'Neurological Effects in the Offspring After Switching From Tobacco Cigarettes to E-Cigarettes During Pregnancy in a Mouse Model', Toxicological Sciences, vol. 172, no. 1, pp. 191-200.
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Abstract Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a “safer” alternative to tobacco cigarettes during pregnancy, however, there are a limited number of studies to suggest that it is actually “safe.” Balb/C female mice were exposed to ambient air (n = 8; Sham), or tobacco cigarette smoke (n = 8; SE) before gestation, during gestation and lactation. A third group was exposed to cigarette smoke before gestation followed by e-cigarette aerosols during gestation and lactation (n = 8; Switch). Male offspring (12-week old, n = 10–14/group) underwent behavioral assessments to investigate short-term memory, anxiety, and activity using the novel object recognition and elevated plus maze tests. Brains were collected at postnatal day (P)1, P20, and Week 13 for global DNA methylation, epigenetic gene expression, and neuronal cell counts. The offspring from mothers switching to e-cigarettes exhibited no change in exploration/activity but showed a decrease in global DNA methylation, Aurora Kinase (Aurk) A and AurkB gene expression and a reduction in neuronal cell numbers in the cornu ammonis 1 region of the dorsal hippocampus compared with the SE group. Continuous tobacco cigarette smoke exposure during pregnancy resulted in marked neurological deficits in the offspring. Switching to e-cigarettes during pregnancy reduced these neurological deficits compared with cigarette smoke exposure. However, neurological changes were still observed, so we therefore conclude that e-cigarette use during pregnancy is not advised.

Nguyen, TMC & Hoang, DB 2019, 'S-MANAGE protocol for provisioning IoT applications on demand', Journal of Telecommunications and the Digital Economy, vol. 7, no. 3, pp. 37-57.
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Internet of Things (IoT)-based services have started making an impact in various domains, such as agriculture, smart farming, smart cities, personal health, and critical infrastructures. Sensor/IoT devices have become one of the indispensable elements in these IoT systems and services. However, their development is restricted by the rigidity of the current network infrastructure, which accommodates heterogeneous physical devices. Software-Defined Networking-Network Functions Virtualization (SDN-NFV) has emerged as a service-enabling solution, supporting network and network function programmability. Provisioning IoT applications on demand is a natural application of programmability. However, these technologies cannot be directly deployed in the sensing/monitoring domain due to the differences in the functionality of SDN network devices and sensor/IoT devices, as well as the limitation of resources in IoT devices. This paper proposes an S-MANAGE protocol that preserves the SDN-NFV paradigm but provides a practical solution in controlling and managing IoT resources for provisioning IoT applications on demand. S-MANAGE is proposed as a new southbound protocol between the software-defined IoT controller and its IoT elements. The paper presents the design of S-MANAGE and demonstrates its use in provisioning IoT services dynamically.

Ni, J, Bongers, A, Chamoli, U, Bucci, J, Graham, P & Li, Y 2019, 'In Vivo 3D MRI Measurement of Tumour Volume in an Orthotopic Mouse Model of Prostate Cancer', Cancer Control, vol. 26, no. 1, pp. 107327481984659-107327481984659.
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Prostate cancer (CaP) is the most commonly diagnosed cancer in males in western countries. Orthotopic implantation is considered as an ideal xenograft model for CaP study, and noninvasive measurement of tumor volume changes is important for monitoring responses to anticancer therapies. In this study, the T2-weighted fast spin echo sequence magnetic resonance imaging (MRI) was performed on a CaP orthotopic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model weekly for 6 weeks post PC-3 CaP cell inoculation, and the fat signal was suppressed using a chemical shift-selective pulse. Subsequently, the MRI data were imported into the image processing software Avizo Standard and stacked into three-dimensional (3D) volumes. Our results demonstrate that MRI, combined with 3D reconstruction, is a feasible and sensitive method to assess tumor growth in a PC-3 orthotopic CaP mouse model and this established monitoring approach is promising for longitudinal observation of CaP xenograft development after anticancer therapy in vivo. Further investigation is needed to validate this protocol in a larger cohort of mice to generate enough statistical power.

Nielson, R, Glasgow, P & Coutts, A 2019, 'Training load monitoring and management in athletes', Journal of Science and Medicine in Sport, vol. 22, pp. S10-S10.
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Oliver, B, Tonga, K, Darley, D, Rutting, S, Zhang, X, Chen, H & Wang, G 2019, 'COPD treatment choices based on blood eosinophils: are we there yet?', Breathe, vol. 15, no. 4, pp. 318-323.
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Eosinophils are increasingly being recognised as an important characteristic feature of COPD. Patients with COPD and eosinophilic inflammation tend to respond to steroid therapy; however, many questions remain regarding the optimum measurement. Eosinophilic inflammation may be defined based on various sampling techniques, including eosinophil levels in blood, sputum, bronchoalveolar lavage or biopsy, which leads to inconsistencies in its definition. Blood eosinophils may increase in conjunction with sputum eosinophils during COPD exacerbations and therefore may be a good surrogate marker of airway eosinophilic inflammation. However, the timing of the blood eosinophil measurement, the stability of the eosinophil count and the threshold used in different studies are variable. The use of blood eosinophil count to direct biological therapies in COPD has also had variable outcomes. Eosinophilic inflammation has an important role in COPD management; however, its use as the optimum biomarker still needs further investigation.Key pointsEosinophilia may play a significant role in the pathogenesis of COPD.Eosinophilic inflammation in COPD can be steroid responsive; however, eosinophilic inflammation is variable, and caution needs to be taken with measurements and the thresholds used.The long-term effects of reducing eosinophil levels in COPD is unclear.Educational aimsTo explore current knowledge of eosinophils in COPD.To explore the relationship between eosinophilia and corticosteroid use.To understand the limitations of asses...

O'Loughlin, I & Newton-John, TRO 2019, '‘Dis-comfort eating’: An investigation into the use of food as a coping strategy for the management of chronic pain', Appetite, vol. 140, pp. 288-297.
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© 2019 Objectives: Chronic pain and obesity are major public health concerns. Animal and human models have demonstrated that eating high-sugar nutrient-dense foods confers analgesic effects. Moreover, recent research suggests that people with chronic pain may “comfort eat” to cope with their pain. Given the harmful impact of obesity on chronic pain, it is critical to determine whether pain elicits comfort eating amongst individuals with chronic pain to ensure that this potentially maladaptive pain coping strategy is not overlooked in chronic pain treatment. Therefore, this study aimed to: determine whether chronic pain intensity predicts pain-induced comfort eating and identify mediators of this relationship; to determine whether pain-induced comfort eating predicts elevated BMI; and to establish whether BMI predicts chronic pain interference. Methods: This study utilised a cross-sectional online survey design and a sample of 151 adults with chronic pain. Results: Over three-quarters of this chronic pain sample reported engaging in pain-induced comfort eating. Chronic pain intensity did not significantly predict pain-induced comfort eating. However, there was a significant indirect effect of chronic pain intensity on pain-induced comfort eating through stress—but not experiential avoidance or pain catastrophising. As predicted, pain-induced comfort eating significantly predicted increased BMI, and BMI in turn significantly predicted greater chronic pain interference. Discussion: This study indicates that pain-induced comfort eating is both common and harmful amongst individuals with chronic pain, across the entire BMI spectrum. Pain-induced comfort eating and stress have emerged as promising chronic pain treatment targets. The findings are discussed and interpreted in light of extant research and theory, as well as limitations of the current study. Future research directions and clinical implications are also considered.

Ong, J, van den Berg, A, Faiz, A, Boudewijn, I, Timens, W, Vermeulen, C, Oliver, B, Kok, K, Terpstra, M, van den Berge, M, Brandsma, C-A & Kluiver, J 2019, 'Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts', International Journal of Molecular Sciences, vol. 20, no. 20, pp. 5176-5176.
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Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns. Our aim was to identify the effect of current smoking on miRNA expression in primary lung fibroblasts. Small RNA sequencing was performed on lung fibroblasts from nine current and six ex-smokers with normal lung function. MiR-335-5p and miR-335-3p were significantly downregulated in lung fibroblasts from current compared to ex-smokers (false discovery rate (FDR) <0.05). Differential miR-335-5p expression was validated with RT-qPCR (p-value = 0.01). The results were validated in lung tissue from current and ex-smokers and in bronchial biopsies from non-diseased smokers and never-smokers (p-value <0.05). The methylation pattern of the miR-335 host gene, determined by methylation-specific qPCR, did not differ between current and ex-smokers. To obtain insights into the genes regulated by miR-335-5p in fibroblasts, we overlapped all proven miR-335-5p targets with our previously published miRNA targetome data in lung fibroblasts. This revealed Rb1, CARF, and SGK3 as likely targets of miR-335-5p in lung fibroblasts. Our study indicates that miR-335-5p downregulation due to current smoking may affect its function in lung fibroblasts by targeting Rb1, CARF and SGK3.

Ong, M, Cheng, J, Jin, X, Lao, W, Johnson, M, Tan, Y & Qu, X 2019, 'Paeoniflorin extract reverses dexamethasone-induced testosterone over-secretion through downregulation of cytochrome P450 17A1 expression in primary murine theca cells', Journal of Ethnopharmacology, vol. 229, pp. 97-103.
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© 2018 Elsevier B.V. Ethnopharmacological relevance: Polycystic Ovarian Syndrome (PCOS) is a complex endocrine and reproductive disorder. A main hallmark includes increased androgen production. The root of Paeonia lactiflora Pall. (Bai Shao) is used in Chinese herbal medicine for reproductive disorders, however its effects and mechanisms on ovarian theca cells has not yet been fully elucidated. Aim of the study: The aim of this study was to evaluate effect of paeoniflorin extract (PFE), the main constituents of Bai Shao, on androgen production in ovarian theca cells. Materials and methods: Primary murine theca cells were treated with concentrations of PFE (1–100 µg/mL) in the presence of dexamethasone (10 µM) with media-only treated cells used as the control. After 24 h, culture media was collected for biochemistry assays of testosterone and progesterone. Expression of key steroidogenic enzymes, cholesterol side-chain cleavage (CYP11A1) and 17α-hydroxylase (CYP17A1) was characterized using immunofluorescence staining, immunoblotting and qRT-PCR. Results: Dexamethasone significantly enhanced testosterone secretion (P < 0.05 vs. the control cells). PFE reversed over-production of testosterone induced by dexamethasone in a dose-dependent manner. The treatment with PFE also normalized production of progesterone in dexamethasone-treated cells. Expression of CYP11A1 and CYP17A1 in the theca cells were visualised by immunofluorescence staining. All doses of PFE significantly inhibited CYP17A1 expression detected by immunoblotting, but only 100 µg/mL of PFE downregulated CYP11A1 expression and reduced CYP11A1 significantly in dexamethasone-treated theca cells. Conclusions: PFE may reduce over-secretion of testosterone in theca cells through downregulation of CYP17A1 and CYP11A1. These findings provide scientific evidence to treat ovarian hyperandrogenism with the root of Paeonia lactiflora Pall.

Pelegri, NG, Gorrie, CA & Santos, J 2019, 'Rat Hippocampal Neural Stem Cell Modulation Using PDGF, VEGF, PDGF/VEGF, and BDNF', Stem Cells International, vol. 2019, pp. 1-12.
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Neural stem cells have become the focus of many studies as they have the potential to differentiate into all three neural lineages. This may be utilised to develop new and novel ways to treat neurological conditions such as spinal cord and brain injuries, especially if the stem cells can be modulated in vivo without additional invasive surgical procedures. This research is aimed at investigating the effects of the growth factors vascular endothelial growth factor, platelet-derived growth factor, brain-derived neurotrophic factor, and vascular endothelial growth factor/platelet-derived growth factor on hippocampal-derived neural stem cells. Cell growth and differentiation were assessed using immunohistochemistry and glutaminase enzyme assay. Cells were cultured for 14 days and treated with different growth factors at two different concentrations 20 ng/mL and 100 ng/mL. At 2 weeks, cells were fixed, and immunohistochemistry was conducted to determine cellular differentiation using antibodies against GFAP, nestin, OSP, and NF200. The cell medium supernatant was also collected during treatment to determine glutaminase levels secreted by the cells as an indicator of neural differentiation. VEGF/PDGF at 100 ng/mL had the greatest influence on cellular proliferation of HNSC, which also stained positively for nestin, OSP, and NF200. In comparison, HNSC in other treatments had poorer cell health and adhesion. HNSC in all treatment groups displayed some differentiation markers and morphology, but this is most significant in the 100 ng/ml VEGF/PDGF treatment. VEGF/PDGF combination produced the optimal effect on the HNSCs inducing the differentiation pathway exhibiting oligodendrocytic and neuronal markers. This is a promising finding that should be further investigated in the brain and spinal cord injury.

Pham, DD, Lee, SK, Shin, C, Kim, NH, Eisman, JA, Center, JR, Nguyen, TV & Leem, CH 2019, 'Koreans Do Not Have Higher Percent Body Fat than Australians: Implication for the Diagnosis of Obesity in Asians', Obesity, vol. 27, no. 11, pp. 1892-1897.
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ObjectiveIt has been assumed that, for a given BMI, Asians have higher percent body fat (PBF) than Caucasians. As a result, it has been suggested that the BMI threshold for diagnosing obesity in Asians be lowered to less than  30 kg/m2. This study sought to compare PBF between Koreans and Australians.MethodsWhole‐body fat mass and PBF were measured in 1,211 Koreans and 1,006 Australians using dual‐energy x‐ray absorptiometry (Lunar Prodigy; GE Healthcare, Madison, Wisconsin). The two groups were then matched for age and BMI by the propensity score method.ResultsFor a given age and BMI, Koreans had lower PBF than Australians, and the difference was statistically significant in women (mean difference: −2.13%; 95% CI: −2.61% to −1.65%) but not in men (difference: −0.54%; 95% CI: −1.22% to 0.14%). Matched‐pair analysis (423 pairs of women and 208 pairs of men) also showed that Korean women had statistically lower PBF than their Australian counterparts (P < 0.001).ConclusionsIn individuals aged 60 years and older, Koreans do not have higher PBF than Australians after adjusting for BMI. These results suggest that there is no evidence for lowering the BMI threshold for the diagnosis of obesity in elderly Koreans.

Phillips, J 2019, 'Humanitarian disasters', International Journal of Palliative Nursing, vol. 25, no. 9, pp. 419-419.
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Phillips, J, Bloomer, M & Mills, J 2019, 'Extending palliative care for underserved populations: Time to act', Collegian, vol. 26, no. 6, pp. 607-608.
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Phillips, JL, Heneka, N, Bhattarai, P, Fraser, C & Shaw, T 2019, 'Effectiveness of the spaced education pedagogy for clinicians’ continuing professional development: a systematic review', Medical Education, vol. 53, no. 9, pp. 886-902.
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ContextEnsuring clinical practice reflects current evidence is challenging given the rapid proliferation of new knowledge. Changing entrenched clinical behaviours and facilitating the adoption of best practice evidence requires a range of strategies, including affordable, scalable and effective continuing professional development (CPD). Yet, identifying the CPD delivery method most likely to effectively change and improve patient outcomes is difficult given the variability in the evidence for different learning approaches. Although there is moderate level evidence for outreach education, audit and feedback, and face‐to‐face or online learning, little is known about the capacity of spaced education to change ineffective clinical practice(s). Spaced education harnesses the power of spacing, repetition and testing learning content to increase topic‐specific knowledge. Although spaced education is widely used in undergraduate and postgraduate medical programmes, its effectiveness as a CPD delivery method that improves patient outcomes is less certain.AimTo determine the effectiveness of the spaced education CPD programmes to change targeted clinical knowledge and practice(s) to improve patient outcomes.MethodA systematic review, appraising the spaced education CPD evidence generated from searching six specialist medical and psychosocial databases. Studies published in English peer‐reviewed journals from 1 January, 2000 to 31 August, 2018 were eligible for inclusion. A modified Kirkpatrick four levels of evaluation framework assisted with appraising the effect of spaced education CPD interventions on clinicians and patients.ResultsOf the 2396 studies identified, 17 met the inclusion criteria, involving 2701 practising clinicians f...

Phillips, JL, Heneka, N, Lovell, M, Lam, L, Davidson, P, Boyle, F, McCaffrey, N, Fielding, S & Shaw, T 2019, 'A phase III wait-listed randomised controlled trial of novel targeted inter-professional clinical education intervention to improve cancer patients’ reported pain outcomes (The Cancer Pain Assessment (CPAS) Trial): study protocol', Trials, vol. 20, no. 1.
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© 2019 The Author(s). Background: Variations in care models contribute to cancer pain being under-recognised and under-treated in half of all patients with cancer. International and national cancer pain management guidelines are achievable with minimal investment but require practice changes. While much of the cancer pain research over the preceding decades has focused on management interventions, little attention has been given to achieving better adherence to recommended cancer pain guideline screening and assessment practices. This trial aims to reduce unrelieved cancer pain by improving cancer and palliative doctors' and nurses' ('clinicians') pain assessment capabilities through a targeted inter-professional clinical education intervention delivered to participants' mobile devices ('mHealth'). Methods: A wait-listed, randomised control trial design. Cancer and/or palliative care physicians and nurses employed at one of the six participating sites across Australia will be eligible to participate in this trial and, on enrolment, will be allocated to the active or wait-listed arm. Participants allocated to the active arm will be invited to complete the mHealth cancer pain assessment intervention. In this trial, mHealth is defined as medical or public health practice supported by mobile devices (i.e. phones, patient monitoring devices, personal digital assistants and other wireless devices). This mHealth intervention integrates three evidence-based elements, namely: the COM-B theoretical framework; spaced learning pedagogy; and audit and feedback. This intervention will be delivered via the QStream online platform to participants' mobile devices over four weeks. The trial will determine if a tailored mHealth intervention, targeting clinicians' cancer pain assessment capabilities, is effective in reducing self-reported cancer pain scores, as measured by a Numerical Rating Scale (NRS). Discussion: If this mHealth intervention is found to be effective, in...

Phillips, JL, Lobb, EA, Bellemore, F, Hays, T & Currow, DC 2019, '‘Through the eyes of the dying’—Identifying who may benefit from bereavement follow-up: A qualitative study', Collegian, vol. 26, no. 6, pp. 615-620.
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© 2019 Introduction: Bereavement support is an integral element of palliative care. Emerging evidence stipulates that bereavement support should be reserved for those most at risk of poor outcomes. While this evidence makes identifying those at risk of experiencing a complex bereavement a necessary first step, it has been difficult to arrive at a consensus as to whom that should be. Aim: To explore whether palliative care in-patients with advanced disease are concerned about the bereavement needs of others and, if so, is it their next-of-kin. Design: A qualitative study using semi-structured interviews, and thematic analysis using a constant comparative method. Setting/participants: Patients identified by their physicians as being aware of their limited prognosis (n = 19) in a specialist palliative care service in Sydney, Australia. Findings: Three key themes emerged: 1) Families considered close and supportive may not require bereavement follow-up; 2) Families with previous significant losses or who have more complex lives are perceived by patients as having greater risk; and 3) Asking palliative care patients about whom they are most concerned in their network after their death is difficult but possible. Conclusions: There are potentially people in the palliative patients’ networks who may be in need of bereavement support, but who are unlikely to be informed about available bereavement services. New strategies are needed to identify people who may benefit from bereavement support.

Pluss, MA, Bennett, KJM, Novak, AR, Panchuk, D, Coutts, AJ & Fransen, J 2019, 'Esports: The Chess of the 21st Century', Frontiers in Psychology, vol. 10.
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For many decades, researchers have explored the true potential of human achievement. The expertise field has come a long way since the early works of de Groot (1965) and Chase and Simon (1973). Since then, this inquiry has expanded into the areas of music, science, technology, sport, academia, and art. Despite the vast amount of research to date, the capability of study methodologies to truly capture the nature of expertise remains questionable. Some considerations include (i) the individual bias in the retrospective recall of developmental activities, (ii) the ability to develop ecologically valid tasks, and (iii) difficulties capturing the influence of confounding factors on expertise. This article proposes that expertise research in electronic sports (esports) presents an opportunity to overcome some of these considerations. Esports involves individuals or teams of players that compete in video game competitions via human-computer interaction. Advantages of applying the expert performance approach in esports include (i) developmental activities are objectively tracked and automatically logged online, (ii) the constraints of representative tasks correspond with the real-world environment of esports performance, and (iii) expertise has emerged without the influence of guided systematic training environments. Therefore, this article argues that esports research provides an ideal opportunity to further advance research on the development and assessment of human expertise.

Poon, J, Cui, Y, Valls Miro, J & Matsubara, T 2019, 'Learning from demonstration for locally assistive mobility aids', International Journal of Intelligent Robotics and Applications, vol. 3, no. 3, pp. 255-268.
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© 2019, The Author(s). Active assistive systems for mobility aids are largely restricted to environments mapped a-priori, while passive assistance primarily provides collision mitigation and other hand-crafted behaviors in the platform’s immediate space. This paper presents a framework providing active short-term assistance, combining the freedom of location independence with the intelligence of active assistance. Demonstration data consisting of on-board sensor data and driving inputs is gathered from an able-bodied expert maneuvring the mobility aid around a generic interior setting, and used in constructing a probabilistic intention model built with Radial Basis Function Networks. This allows for short-term intention prediction relying only upon immediately available user input and on-board sensor data, to be coupled with real-time path generation based upon the same expert demonstration data via Dynamic Policy Programming, a stochastic optimal control method. Together these two elements provide a combined assistive mobility system, capable of operating in restrictive environments without the need for additional obstacle avoidance protocols. Experimental results in both simulation and on the University of Technology Sydney semi-autonomous wheelchair in settings not seen in training data show promise in assisting users of power mobility aids.

Qiao, C, Lu, L, Yang, L & Kennedy, PJ 2019, 'Identifying Brain Abnormalities with Schizophrenia Based on a Hybrid Feature Selection Technology', Applied Sciences, vol. 9, no. 10, pp. 2148-2148.
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Many medical imaging data, especially the magnetic resonance imaging (MRI) data, usually have a small sample size, but a large number of features. How to reduce effectively the data dimension and locate accurately the biomarkers from such kinds of data are quite crucial for diagnosis and further precision medicine. In this paper, we propose a hybrid feature selection method based on machine learning and traditional statistical approaches and explore the brain abnormalities of schizophrenia by using the functional and structural MRI data. The results show that the abnormal brain regions are mainly distributed in the supramarginal gyrus, cingulate gyrus, frontal gyrus, precuneus and caudate, and the abnormal functional connections are related to the caudate nucleus, insula and rolandic operculum. In addition, some complex network analyses based on graph theory are utilized on the functional connection data, and the results demonstrate that the located abnormal functional connections in brain can distinguish schizophrenia patients from healthy controls. The identified abnormalities in brain with schizophrenia by the proposed hybrid feature selection method show that there do exist some abnormal brain regions and abnormal disruption of the network segregation and network integration for schizophrenia, and these changes may lead to inaccurate and inefficient information processing and synthesis in the brain, which provide further evidence for the cognitive dysmetria of schizophrenia.

Rafeie, M, Hosseinzadeh, S, Huang, J, Mihandoust, A, Warkiani, ME & Taylor, RA 2019, 'New insights into the physics of inertial microfluidics in curved microchannels. II. Adding an additive rule to understand complex cross-sections', Biomicrofluidics, vol. 13, no. 3, pp. 034118-034118.
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Curved microchannels allow controllable microparticle focusing, but a full understanding of particle behavior has been limited—even for simple rectangular and trapezoidal shapes. At present, most microfluidic particle separation literature is dedicated to adding “internal” complexity (via sheath flow or obstructions) to relatively simple cross-sectional channel shapes. We propose that, with sufficient understanding of particle behavior, an equally viable pathway for microparticle focusing could utilize complex “external” cross-sectional shapes. By investigating three novel, complex spiral microchannels, we have found that it is possible to passively focus (6, 10, and 13 μm) microparticles in the middle of a convex channel. Also, we found that in concave and jagged channel designs, it is possible to create multiple, tight focusing bands. In addition to these performance benefits, we report an “additive rule” herein, which states that complex channels can be considered as multiple, independent, simple cross-sectional shapes. We show with experimental and numerical analysis that this new additive rule can accurately predict particle behavior in complex cross-sectional shaped channels and that it can help to extract general inertial focusing tendencies for suspended particles in curved channels. Overall, this work provides simple, yet reliable, guidelines for the design of advanced curved microchannel cross sections.

Rafeie, M, Hosseinzadeh, S, Taylor, RA & Warkiani, ME 2019, 'New insights into the physics of inertial microfluidics in curved microchannels. I. Relaxing the fixed inflection point assumption', Biomicrofluidics, vol. 13, no. 3, pp. 034117-034117.
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Inertial microfluidics represents a powerful new tool for accurately positioning cells and microparticles within fluids for a variety of biomedical, clinical, and industrial applications. In spite of enormous advancements in the science and design of these devices, particularly in curved microfluidic channels, contradictory experimental results have confounded researchers and limited progress. Thus, at present, a complete theory which describes the underlying physics is lacking. We propose that this bottleneck is due to one simple mistaken assumption—the locations of inflection points of the Dean velocity profile in curved microchannels are not fixed, but can actually shift with the flow rate. Herein, we propose that the dynamic distance (δ) between the real equilibrium positions and their nearest inflection points can clearly explain several (previously) unexplained phenomena in inertial microfluidic systems. More interestingly, we found that this parameter, δ, is a function of several geometric and operational parameters, all of which are investigated (in detail) here with a series of experiments and simulations of different spiral microchannels. This key piece of understanding is expected to open the door for researchers to develop new and more effective inertial microfluidic designs.

Rao, A, DiGiacomo, M, Newton, PJ, Phillips, JL & Hickman, LD 2019, 'Meditation and Secondary Prevention of Depression and Anxiety in Heart Disease: a Systematic Review', Mindfulness, vol. 10, no. 1, pp. 1-14.
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Heart disease is the leading cause of global mortality, accounting for 13.7 million deaths annually. Optimising depression and anxiety symptoms in adults with heart disease is an international priority. Heart disease secondary prevention is best achieved through implementation of sustainable pharmacological and non-pharmacological interventions, including meditation. Meditation is a means of generating self-awareness and has implications for enhanced self-management of depression and anxiety symptoms. This review aims to identify high-level quantitative evidence for meditation interventions designed to improve depression and/or anxiety symptoms among adults with heart disease and ascertain the most important elements of meditation interventions that facilitate positive depression and/or anxiety outcomes. This systematic review and narrative synthesis was completed in accordance with the PRISMA Statement and has adhered to the Cochrane Risk of Bias guideline. Six databases were searched between 1975 and 2017. Statistically significant outcomes were demonstrated in over half (5/9) of phase II meditation studies for depression and/or anxiety and involved 477 participants. Meditation interventions that generated positive outcomes for depression and/or anxiety included elements such as focused attention to body parts (or body scan) (3/4 studies) and/or group meetings (4/5 studies). Meditation is a means of reframing heart disease outpatient services towards an integrated model of care. Future adequately powered phase III studies are needed to confirm which meditation elements are associated with reductions in depression and anxiety; and the differential effects between concentrative and mindfulness-based meditation types among adults with heart disease.

Raoufi, MA, Mashhadian, A, Niazmand, H, Asadnia, M, Razmjou, A & Warkiani, ME 2019, 'Experimental and numerical study of elasto-inertial focusing in straight channels', Biomicrofluidics, vol. 13, no. 3, pp. 034103-034103.
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Elasto-inertial microfluidics has drawn significant attention in recent years due to its enhanced capabilities compared to pure inertial systems in control of small microparticles. Previous investigations have focused mainly on the applications of elasto-inertial sorting, rather than studying its fundamentals. This is because of the complexity of simulation and analysis, due to the presence of viscoelastic force. There have been some investigative efforts on the mechanisms of elasto-inertial focusing in straight channels; however, these studies were limited to simple rectangular channels and neglected the effects of geometry and flow rates on focusing positions. Herein, for the first time, we experimentally and numerically explore the effects of elasticity accompanying channel cross-sectional geometry and sample flow rates on the focusing phenomenon in elasto-inertial systems. The results reveal that increasing the aspect ratio weakens the elastic force more than inertial force, causing a transition from one focusing position to two. In addition, they show that increasing the angle of a channel corner causes the elastic force to push the particles more efficiently toward the center over a larger area of the channel cross section. Following on from this, we proposed a new complex straight channel which demonstrates a tighter focusing band compared to other channel geometries. Finally, we focused Saccharomyces cerevisiae cells (3–5 μm) in the complex channel to showcase its capability in focusing small-size particles. We believe that this research work improves the understanding of focusing mechanisms in viscoelastic solutions and provides useful insights into the design of elasto-inertial microfluidic devices.

Raoufi, MA, Moshizi, SA, Razmjou, A, Wu, S, Ebrahimi Warkiani, M & Asadnia, M 2019, 'Development of a Biomimetic Semicircular Canal With MEMS Sensors to Restore Balance', IEEE Sensors Journal, vol. 19, no. 23, pp. 11675-11686.
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© 2001-2012 IEEE. A third of adults over the age of 50 suffer from chronic impairment of balance, posture, and/or gaze stability due to partial or complete impairment of the sensory cells in the inner ear responsible for these functions. The consequences of impaired balance organ can be dizziness, social withdrawal, and acceleration of the further functional decline. Despite the significant progress in biomedical sensing technologies, current artificial vestibular systems fail to function in practical situations and in very low frequencies. Herein, we introduced a novel biomechanical device that closely mimics the human vestibular system. A microelectromechanical systems (MEMS) flow sensor was first developed to mimic the vestibular haircell sensors. The sensor was then embedded into a three-dimensional (3D) printed semicircular canal and tested at various angular accelerations in the frequency range from 0.5Hz to 1.5Hz. The miniaturized device embedded into a 3D printed model will respond to mechanical deflections and essentially restore the sense of balance in patients with vestibular dysfunctions. The experimental and simulation studies of semicircular canal presented in this work will pave the way for the development of balance sensory system, which could lead to the design of a low-cost and commercially viable medical device with significant health benefits and economic potential.

Raymond, B, Luckett, T, Johnson, M, Hutchinson, A, Lovell, M & Phillips, J 2019, 'Low-intensity educational interventions supporting self-management to improve outcomes related to chronic breathlessness: a systematic review', npj Primary Care Respiratory Medicine, vol. 29, no. 1, p. 41.
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AbstractChronic breathlessness is debilitating and frightening, often resulting in emergency department presentations with acute-on-chronic breathlessness. Self-management is complex, involving 14 components as identified by the Practical Systematic Review in Self-Management Support (PRISMS). Low-intensity educational interventions that support breathlessness self-management through written/visual educational materials, alongside limited health professional support, are available. Our aim was to describe components of low-intensity educational interventions that support and improve self-management for adults with chronic breathlessness and evaluate their efficacy for improving breathlessness-related outcomes. A systematic review was conducted, including RCTs that compared these interventions with usual care in adults with chronic disease. Synthesis took a narrative approach utilizing the PRISMS taxonomy and Template for Intervention Description and Replication (TIDieR) checklist. Of the 1948 articles identified, 7 met criteria reporting 7 RCTs using 6 interventions. Studies utilized 12 out of 14 PRISMS components, the most frequent being training/rehearsal for psychological strategies. Evidence for effectiveness was inconsistent and attempts to identify beneficial components were confounded by intervention complexity and heterogeneity. The optimal content and delivery of low-intensity educational interventions that support self-management to improve chronic breathlessness-related outcomes in adults cannot be defined from current published literature. Future research should incorporate more detailed, standardized reporting to enable comparison and meta-analysis.

Razavi Bazaz, S, Kashaninejad, N, Azadi, S, Patel, K, Asadnia, M, Jin, D & Ebrahimi Warkiani, M 2019, 'Microfluidics: Rapid Softlithography Using 3D‐Printed Molds (Adv. Mater. Technol. 10/2019)', Advanced Materials Technologies, vol. 4, no. 10, pp. 1970056-1970056.
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Razavi Bazaz, S, Kashaninejad, N, Azadi, S, Patel, K, Asadnia, M, Jin, D & Ebrahimi Warkiani, M 2019, 'Rapid Softlithography Using 3D‐Printed Molds', Advanced Materials Technologies, vol. 4, no. 10, pp. 1900425-1900425.
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AbstractPolydimethylsiloxane (PDMS) is a long‐standing material of significant interest in microfluidics due to its unique features. As such, rapid prototyping of PDMS‐based microchannels is of great interest. The most prevalent and conventional method for fabrication of PDMS‐based microchips relies on softlithography, the main drawback of which is the preparation of a master mold, which is costly and time‐consuming. To prevent the attachment of PDMS to the master mold, silanization is necessary, which can be detrimental for cellular studies. Additionally, using coating the mold with a cell‐compatible surfactant adds extra preprocessing time. Recent advances in 3D printing have shown great promise in expediting microfabrication. Nevertheless, current 3D printing techniques are sub‐optimal for PDMS softlithography. The feasibility of producing master molds suitable for rapid softlithography is demonstrated using a newly developed 3D‐printing resin. Moreover, the utility of this technique is showcased for a number of widely used applications, such as concentration gradient generation, particle separation, cell culture (to show biocompatibility of the process), and fluid mixing. This can open new opportunities for biologists and scientists with minimum knowledge of microfabrication to build functional microfluidic devices for their basic and applied research.

Rezaei, M, Winter, M, Zander-Fox, D, Whitehead, C, Liebelt, J, Warkiani, ME, Hardy, T & Thierry, B 2019, 'A Reappraisal of Circulating Fetal Cell Noninvasive Prenatal Testing', Trends in Biotechnology, vol. 37, no. 6, pp. 632-644.
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© 2018 Elsevier Ltd New tools for higher-resolution fetal genome analysis including microarray and next-generation sequencing have revolutionized prenatal screening. This article provides commentary on this rapidly advancing field and a future perspective emphasizing circulating fetal cell (CFC) utility. Despite the tremendous technological challenges associated with their reliable and cost-effective isolation from maternal blood, CFCs have a strong potential to bridge the gap between the diagnostic sensitivity of invasive procedures and the desirable noninvasive nature of cell-free fetal DNA (cffDNA). Considering the rapid advances in both rare cell isolation and low-input DNA analysis, we argue here that CFC-based noninvasive prenatal testing is poised to be implemented clinically in the near future.

Rutting, S, Xenaki, D, Malouf, M, Horvat, JC, Wood, LG, Hansbro, PM & Oliver, BG 2019, 'Short-chain fatty acids increase TNFα-induced inflammation in primary human lung mesenchymal cells through the activation of p38 MAPK', American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 316, no. 1, pp. L157-L174.
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Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have anti-inflammatory properties and could potentially be used for the treatment of inflammatory diseases, including asthma. The direct effects of SCFAs on inflammatory responses in primary human lung mesenchymal cells have not been assessed. We investigated whether SCFAs can protect against tumor necrosis factor (TNF)α-induced inflammation in primary human lung fibroblasts (HLFs) and airway smooth muscle (ASM) cells in vitro. HLFs and ASM cells were exposed to SCFAs, acetate (C2:0), propionate (C3:0), and butyrate (C4:0) (0.01–25 mM) with or without TNFα, and the release of proinflammatory cytokines, IL-6, and CXCL8 was measured using ELISA. We found that none of the SCFAs suppressed TNFα-induced cytokine release. On the contrary, challenge with supraphysiological concentrations (10–25 mM), as might be used therapeutically, of propionate or butyrate in combination with TNFα resulted in substantially greater IL-6 and CXCL8 release from HLFs and ASM cells than challenge with TNFα alone, demonstrating synergistic effects. In ASM cells, challenge with acetate also enhanced TNFα-induced IL-6, but not CXCL8 release. Synergistic upregulation of IL-6 and CXCL8 was mediated through the activation of free fatty acid receptor (FFAR)3, but not FFAR2. The signaling pathways involved were further examined using specific inhibitors and immunoblotting, and responses were found to be mediated through p38 MAPK signaling. This study demonstrates that proinflammatory, rather than anti-inflammatory effects of SCFAs are evident in lung mesenchymal cells.

Rutting, S, Zakarya, R, Bozier, J, Xenaki, D, Horvat, JC, Wood, LG, Hansbro, PM & Oliver, BG 2019, 'Dietary Fatty Acids Amplify Inflammatory Responses to Infection through p38 MAPK Signaling', American Journal of Respiratory Cell and Molecular Biology, vol. 60, no. 5, pp. 554-568.
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Copyright © 2019 by the American Thoracic Society. Obesity is an important risk factor for severe asthma exacerbations, which are mainly caused by respiratory infections. Dietary fatty acids, which are increased systemically in obese patients and are further increased after high-fat meals, affect the innate immune system and may contribute to dysfunctional immune responses to respiratory infection. In this study we investigated the effects of dietary fatty acids on immune responses to respiratory infection in pulmonary fibroblasts and a bronchial epithelial cell line (BEAS-2B). Cells were challenged with BSA-conjugated fatty acids (v-6 polyunsaturated fatty acids [PUFAs], v-3 PUFAs, or saturated fatty acids [SFAs]) 1/2 the viral mimic polyinosinic:polycytidylic acid (poly[I:C]) or bacterial compound lipoteichoic acid (LTA), and release of proinflammatory cytokines was measured. In both cell types, challenge with arachidonic acid (AA) (v-6 PUFA) and poly(I:C) or LTA led to substantially greater IL-6 and CXCL8 release than either challenge alone, demonstrating synergy. In epithelial cells, palmitic acid (SFA) combined with poly(I:C) also led to greater IL-6 release. The underlying signaling pathways of AA and poly(I:C)- or LTA-induced cytokine release were examined using specific signaling inhibitors and IB. Cytokine production in pulmonary fibroblasts was prostaglandin dependent, and synergistic upregulation occurred via p38 mitogen-activated protein kinase signaling, whereas cytokine production in bronchial epithelial cell lines was mainly mediated through JNK and p38 mitogen-activated protein kinase signaling. We confirmed these findings using rhinovirus infection, demonstrating that AA enhances rhinovirus-induced cytokine release. This study suggests that during respiratory infection, increased levels of dietary v-6 PUFAs and SFAs may lead to more severe airway inflammation and may contribute to and/or increase the severity of asthma exacerbations.

Ryan, S, Kempton, T, Pacecca, E & Coutts, AJ 2019, 'Measurement Properties of an Adductor Strength-Assessment System in Professional Australian Footballers', International Journal of Sports Physiology and Performance, vol. 14, no. 2, pp. 256-259.
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© 2019 Human Kinetics, Inc. Purpose: To examine the measurement properties of an adductor strength-assessment system in professional Australian footballers. Methods: Observational, longitudinal design. Test–retest reliability data were collected from 18 professional Australian footballers from 1 club on the same day during the 2017 Australian Football League season. Week-to-week variation data were collected on 45 professional Australian footballers from 1 club during the same season at 48, 72, and 120 h postmatch (rounds 1–23). Players lay beneath a GroinBar hip-strength testing system in supine position with their knee joints at an angle of 60°. Force (in newtons) was extracted for the left and right limbs of each player and a pain score from 0 to 10 (0 = no pain, 10 = maximum pain) was provided. Coefficient of variation (CV) and smallest worthwhile change were calculated on test–retest data. Signal-to-noise ratio was calculated for each major time point. Mean difference between force scores in a subgroup of players with and without groin pain (n = 18) was collected as evidence of construct validity for the system. Results: Test CV was 6.3% (4.9–9.0%). CV exceeded the smallest worthwhile change on both limbs. Intraclass correlation coefficient was .94. Signal-to-noise ratio ranged from 1.6 to 2.6 on average for 48, 72, and 120 h postmatch. Groin pain had a very likely moderate negative effect on adductor strength (effect size: 0.41). Conclusions: The system possesses greater measurement precision than dynamometry and sphygmomanometer adductor strength-assessment methods in professional Australian footballers. Increased groin pain reduced groin squeeze force production. Practitioners may interpret changes exceeding 6.3% in adductor strength as real.

Sabnis, AB, Chamoli, U & Diwan, AD 2019, 'Answer to the Letter to the Editor of Miao Yu et al. concerning “Is L5-S1 motion segment different from the rest? A radiographic kinematic assessment of 72 patients with chronic low back pain” by AB Sabnis et al. (Eur. Spine J; 27(5):1127–1135)', European Spine Journal, vol. 28, no. 5, pp. 1249-1249.
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Saffari, M, Lin, C-Y, Chen, H & Pakpour, AH 2019, 'The role of religious coping and social support on medication adherence and quality of life among the elderly with type 2 diabetes', Quality of Life Research, vol. 28, no. 8, pp. 2183-2193.
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© 2019, Springer Nature Switzerland AG. Purpose: Type 2 diabetes is a major public health issue particularly in the elderly. Religion may affect the Health Related Quality of Life (HRQoL) in such patients, mediated by factors such as religious coping and social support. This study aimed to investigate the impact of religiosity on medication adherence and HRQoL. Methods: 793 adults (> 65 years old, 45% females) were recruited from 4 diabetes care centers and followed for 1 year. Duke University Religion Index, Spiritual Coping Strategies, Multidimensional Perceived Social Support, Medication Adherence Report Scale, WHOQOL-BREF and Diabetes-specific Quality of Life Questionnaire Module were used for assessment, as well as HbA1c and fasting blood glucose level. Using structural equation modeling, the potential paths were tested between religiosity, medication adherence and HRQoL; social support, religious coping and medication adherence served as the mediators. Results: Religious coping and social support were recognized as the significant mediators between religiosity and medication adherence (CFI = 0.983, TLI = 0.985, and RMSEA = 0.021). The relationships between religiosity and HRQoL were considerably mediated by social support, religious coping and medication adherence and these variables explained 12% and 33% of variances of generic and specific HRQoL, respectively. There was no significant direct effect of religiosity on HRQoL. HbA1c and fasting blood glucose level were successfully loaded on the latent construct of medication adherence (factor loading = 0.51 and 0.44, respectively). Conclusions: The impact of religiosity on medication adherence and HRQoL occurs through the mediators such as religious coping and social support. Therefore, to improve the adherence to treatment and quality of life, interventions may be designed based on these mediators.

Samardzic, K & Rodgers, KJ 2019, 'Cell death and mitochondrial dysfunction induced by the dietary non-proteinogenic amino acid l-azetidine-2-carboxylic acid (Aze)', Amino Acids, vol. 51, no. 8, pp. 1221-1232.
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Samardzic, K & Rodgers, KJ 2019, 'Cytotoxicity and mitochondrial dysfunction caused by the dietary supplement l-norvaline', Toxicology in Vitro, vol. 56, pp. 163-171.
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In addition to the 20 protein amino acids that are encoded for protein synthesis, hundreds of other naturally occurring amino acids, known as non-proteinogenic amino acids (NPAAs) exist. It is well known that some NPAAs are toxic through their ability to mimic protein amino acids, either in protein synthesis or in other metabolic pathways, and this property is utilised by some plants to inhibit the growth of other plants or kill herbivores. L-norvaline is an NPAA readily available for purchase as a dietary supplement. In light of previous evidence of l-norvaline's antifungal, antimicrobial and herbicidal activity, we examined the toxicity of l-norvaline to mammalian cells in vitro and showed that l-norvaline decreased cell viability at concentrations as low as 125 μM, caused necrotic cell death and significant changes to mitochondrial morphology and function. Furthermore, toxicity was reduced in the presence of structurally similar 'protein' amino acids, suggesting l-norvaline's cytotoxicity could be attributed to protein amino acid mimicry.

Sanderson, C, Miller-Lewis, L, Rawlings, D, Parker, D & Tieman, J 2019, '“I want to die in my sleep”—how people think about death, choice, and control: findings from a Massive Open Online Course', Annals of Palliative Medicine, vol. 8, no. 4, pp. 411-419.
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© Annals of Palliative Medicine. Background: Complex social and ethical debates about voluntary assisted dying (euthanasia), palliative care, and advance care planning are presently being worked through in many developed countries, and the policy implications of these discussions for palliative care are potentially very significant. However, community attitudes to death and dying are complex, multilayered, and contain many mixed messages. Methods: Participants posted comments in a Massive Open Online Course (MOOC) on death and dying, entitled Dying2Learn. This provided an opportunity to explore societal and personal attitudes to wishes and beliefs around death and dying. For one activity in the MOOC, participants responded to a question asking them about “the best way to go”. Results: Responses were subjected to thematic analysis, during which they were coded for conceptual categories. This analysis showed how acceptance of death as a natural and normal process, and as a shared event that affects a whole social network, may nonetheless be accompanied by deep reluctance to address the physical process of dying (i.e., “avoidant acceptance”). Conclusions: Our findings highlighted a desire for choice and control in relation to dying, which is a common element in discussions of both advance care planning and palliative care. This same focus may contribute to a perception that voluntary assisted dying/euthanasia is a necessary strategy for ensuring that people have control over their dying process. We discuss the paradox of individuals wanting to have control whilst preferring not to know that they are dying.

Sanderson, C, Sheahan, L, Kochovska, S, Luckett, T, Parker, D, Butow, P & Agar, M 2019, 'Re-defining moral distress: A systematic review and critical re-appraisal of the argument-based bioethics literature', Clinical Ethics, vol. 14, no. 4, pp. 195-210.
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The concept of moral distress comes from nursing ethics, and was initially defined as ‘…when one knows the right thing to do, but institutional constraints make it nearly impossible to pursue the right course of action’. There is a large body of literature associated with moral distress, yet multiple definitions now exist, significantly limiting its usefulness. We undertook a systematic review of the argument-based bioethics literature on this topic as the basis for a critical appraisal, identifying 55 papers for analysis. We found that moral distress is most frequently framed around individual experiences of distress in relation to local practices and constraints, and understood in terms of power relations and workplace hierarchies. This understanding is directly derived from, and often still seen as specific to, nursing. Frequently the perspective of the morally distressed individual is privileged. Understandings of moral distress have evolved towards an ‘occupational health approach’, with the assumption that moral distress should be measured and prevented. Counter-perspectives were identified, highlighting conceptual problems. Based on our review, we propose a redefinition of moral distress: ‘Ethical unease or disquiet resulting from a situation where a clinician believes they have contributed to avoidable patient or community harm through their involvement in an action, inaction or decision that conflicts with their own values’. This definition is specific enough for research use, anchored in clinicians’ professional responsibilities and concerns about harms to patients, framed relationally rather than hierarchically, and amenable to multiple perspectives on any given morally distressing situation.

Santos, J, Milthorpe, B & Padula, M 2019, 'Proteomic Analysis of Cyclic Ketamine Compounds Ability to Induce Neural Differentiation in Human Adult Mesenchymal Stem Cells', International Journal of Molecular Sciences, vol. 20, no. 3, pp. 523-523.
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Neural regeneration is of great interest due to its potential to treat traumatic brain injuries and diseases that impact quality of life. Growth factor mediated differentiation can take up to several weeks to months to produce the cell of interest whereas chemical stimulation may be as minimal as a few hours. The smaller time scale is of great clinical relevance. Adipose derived stem cells (ADSCs) were treated for up to 24 h with a novel differentiation media containing the cyclic ketamine compounds to direct neurogenic induction. The extent of differentiation was investigated by proteome changes occurring during the process. The treatments indicated the ADSCs responded favorably to the neurogenic induction media by presenting a number of morphological cues of neuronal phenotype previously seen and a higher cell population post induction compared to previous studies. Furthermore, approximately 3500 proteins were analyzed and identified by mass spectrometric iTRAQ analyses. The bioinformatics analyses revealed hundreds of proteins whose expression level changes were statistically significant and biologically relevant to neurogenesis and annotated as being involved in neurogenic development. Complementing this, the Bioplex cytokine assay profiles present evidence of decreased panel of stress response cytokines and a relative increase in those involved in neurogenesis.

Santos, J, Milthorpe, BK & Padula, MP 2019, 'Correction: Santos, J., et al. Proteomic Analysis of Cyclic Ketamine Compounds Ability to Induce Neural Differentiation in Human Adult Mesenchymal Stem Cells. International Journal of Molecular Sciences 2019, 20, 523', International Journal of Molecular Sciences, vol. 20, no. 14, pp. 3542-3542.
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The authors wish to make the following corrections to this paper [...]

Sheikhi, M, Movahedizadeh, M, Shahsavari, S & Chen, H 2019, 'The Association between Religious Belief and Drug Adherence Mediated by Religious Coping in Patients with Mental Disorders', Social Health and Behavior, vol. 2, no. 3, pp. 77-77.
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Sheldrick, K, Chamoli, U, Masuda, K, Miyazaki, S, Kato, K & Diwan, AD 2019, 'A novel magnetic resonance imaging postprocessing technique for the assessment of intervertebral disc degeneration—Correlation with histological grading in a rabbit disc degeneration model', JOR SPINE, vol. 2, no. 3.
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AbstractIntroductionEstimation of intervertebral disc degeneration on magnetic resonance imaging (MRI) is challenging. Qualitative schemes used in clinical practice correlate poorly with pain and quantitative techniques have not entered widespread clinical use.MethodsAs part of a prior study, 25 New Zealand white rabbits underwent annular puncture to induce disc degeneration in 50 noncontiguous lumbar discs. At 16 weeks, the animals underwent multi‐echo T2 MRI scanning and were euthanized. The discs were stained and examined histologically. Quantitative T2 relaxation maps were prepared using the nonlinear least squares method. Decay Variance maps were created using a novel technique of aggregating the deviation in the intensity of each echo signal from the expected intensity based on the previous rate of decay.ResultsDecay Variance maps showed a clear and well demarcated nucleus pulposus with a consistent rate of decay (low Decay Variance) in healthy discs that showed progressively more variable decay (higher Decay Variance) with increasing degeneration. Decay Variance maps required significantly less time to generate (1.0 ± 0.0 second) compared with traditional T2 relaxometry maps (5 (±0.9) to 1788.9 (±116) seconds). Histology scores correlated strongly with Decay Variance scores (r = 0.82, P < .01) and weakly with T2 signal intensity (r = 0.32, P < .01) and quantitative T2 relaxometry (r = 0.39, P < .01). Decay Variance had superior sensitivity and specificity for the detection of degenerate discs when compared to T2 signal intensity or Quantitative T2 mapping.ConclusionOur results show that using a multi‐echo ...

Shires, A, Sharpe, L & Newton John, TRO 2019, 'The relative efficacy of mindfulness versus distraction: The moderating role of attentional bias', European Journal of Pain, vol. 23, no. 4, pp. 727-738.
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AbstractBackgroundThis study investigated whether the ability to disengage quickly from pain‐related stimuli moderated the relative efficacy of a mindfulness‐based intervention versus distraction in response to an experimental pain task.MethodsParticipants (n = 100) completed a dot probe task with eye tracking and were then randomized (2:2:1) to receive a mindfulness‐based interoceptive exposure task (MIET), distraction instructions or no instructions (control group) before engaging in the cold pressor test.ResultsParticipants who were allocated to the MIET condition reported a significantly higher pain threshold and distress than the distraction group, although not significantly higher than the control group. Those in the MIET group had improved tolerance compared to both the distraction and control groups. Difficulty disengaging from pain‐related stimuli, as measured by the duration of the first fixation on sensory words, was found to moderate the relative efficacy of mindfulness versus distraction in terms of pain threshold and distress, but not tolerance. Those with difficulty disengaging from sensory pain words benefited less from the MIET. Duration of first fixation on sensory and affective pain words were highly correlated, and duration of first fixation on affective pain words also moderated the relative efficacy of MIET and distraction on threshold, but not distress.ConclusionsThese results show that a single brief session of a mindfulness task was sufficient to change an acute pain experience in comparison with a distraction task, and that those who disengaged quickly from pain words benefited most.Significance...

Shrestha, J, Ghadiri, M, Shanmugavel, M, Razavi Bazaz, S, Vasilescu, S, Ding, L & Ebrahimi Warkiani, M 2019, 'A rapidly prototyped lung-on-a-chip model using 3D-printed molds', Organs-on-a-Chip, vol. 1, pp. 100001-100001.
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Si, L, Eisman, JA, Winzenberg, T, Sanders, KM, Center, JR, Nguyen, TV & Palmer, AJ 2019, 'Microsimulation model for the health economic evaluation of osteoporosis interventions: study protocol', BMJ Open, vol. 9, no. 2, pp. e028365-e028365.
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IntroductionOsteoporosis is a systemic skeletal disease that is characterised by reduced bone strength and increased fracture risk. Osteoporosis-related fractures impose enormous disease and economic burden to the society. Although many treatments and health interventions are proven effective to prevent fractures, health economic evaluation adds evidence to their economic merits. Computer simulation modelling is a useful approach to extrapolate clinical and economic outcomes from clinical trials and it is increasingly used in health economic evaluation. Many osteoporosis health economic models have been developed in the past decades; however, they are limited to academic use and there are no publicly accessible health economic models of osteoporosis.Methods and analysisWe will develop the Australian osteoporosis health economic model based on our previously published microsimulation model of osteoporosis in the Chinese population. The development of the model will follow the recommendations for the conduct of economic evaluations in osteoporosis by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the US branch of the International Osteoporosis Foundation. The model will be a state-transition semi-Markov model with memory. Clinical parameters in the model will be mainly obtained from the Dubbo Osteoporosis Epidemiology Study and the health economic parameters will be collected from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study. Model transparency and validates will be tested using the recommendations from Good Research Practices in Modelling Task Forces. The model will be used in economic evaluations of osteoporosis interventions including pharmaceutical treatments and primary care interventions. A user-friendly graphical user ...

Skorski, S, Mujika, I, Bosquet, L, Meeusen, R, Coutts, AJ & Meyer, T 2019, 'The Temporal Relationship Between Exercise, Recovery Processes, and Changes in Performance', International Journal of Sports Physiology and Performance, vol. 14, no. 8, pp. 1015-1021.
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Physiological and psychological demands during training and competition generate fatigue and reduce an athlete’s sport-specific performance capacity. The magnitude of this decrement depends on several characteristics of the exercise stimulus (eg, type, duration, and intensity), as well as on individual characteristics (eg, fitness, profile, and fatigue resistance). As such, the time required to fully recover is proportional to the level of fatigue, and the consequences of exercise-induced fatigue are manifold. Whatever the purpose of the ensuing exercise session (ie, training or competition), it is crucial to understand the importance of optimizing the period between exercise bouts in order to speed up the regenerative processes and facilitate recovery or set the next stimulus at the optimal time point. This implies having a fairly precise understanding of the fatigue mechanisms that contribute to the performance decrement. Failing to respect an athlete’s recovery needs may lead to an excessive accumulation of fatigue and potentially “nonfunctional overreaching” or to maladaptive training. Although research in this area recently increased, considerations regarding the specific time frames for different physiological mechanisms in relation to exercise-induced fatigue are still missing. Furthermore, recommendations on the timing and dosing of recovery based on these time frames are limited. Therefore, the aim of this article is to describe time courses of recovery in relation to the exercise type and on different physiological levels. This summary supports coaches, athletes, and scientists in their decision-making process by considering the relationship of exercise type, physiology, and recovery.

Smith, CM, Catchpoole, D & Hutvagner, G 2019, 'Non-Coding RNAs in Pediatric Solid Tumors', Frontiers in Genetics, vol. 10.
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© Copyright © 2019 Smith, Catchpoole and Hutvagner. Pediatric solid tumors are a diverse group of extracranial solid tumors representing approximately 40% of childhood cancers. Pediatric solid tumors are believed to arise as a result of disruptions in the developmental process of precursor cells which lead them to accumulate cancerous phenotypes. In contrast to many adult tumors, pediatric tumors typically feature a low number of genetic mutations in protein-coding genes which could explain the emergence of these phenotypes. It is likely that oncogenesis occurs after a failure at many different levels of regulation. Non-coding RNAs (ncRNAs) comprise a group of functional RNA molecules that lack protein coding potential but are essential in the regulation and maintenance of many epigenetic and post-translational mechanisms. Indeed, research has accumulated a large body of evidence implicating many ncRNAs in the regulation of well-established oncogenic networks. In this review we cover a range of extracranial solid tumors which represent some of the rarer and enigmatic childhood cancers known. We focus on two major classes of ncRNAs, microRNAs and long non-coding RNAs, which are likely to play a key role in the development of these cancers and emphasize their functional contributions and molecular interactions during tumor formation.

Smith, MR, Chai, R, Nguyen, HT, Marcora, SM & Coutts, AJ 2019, 'Comparing the Effects of Three Cognitive Tasks on Indicators of Mental Fatigue', The Journal of Psychology, vol. 153, no. 8, pp. 759-783.
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© 2019, © 2019 Taylor & Francis Group, LLC. This investigation assessed the impact of three cognitively demanding tasks on cognitive performance, subjective, and physiological indicators of mental fatigue. Following familiarization, participants completed four testing sessions, separated by 48 h. During each session, participants watched a 45-min emotionally neutral documentary (control) or completed one of the following computer tasks: Psychomotor Vigilance Task (PVT); AX-Continuous Performance Test (AX-CPT); or Stroop Task. Mental fatigue was assessed before and at regular periods for 60 min following the 45-min treatments. Cognitive performance was assessed using 3-min PVT, and task performance. Subjective assessments were conducted using the Brunel Mood Scale, and visual analog scales (VAS). Physiological indicators of mental fatigue included electroencephalography (EEG), and heart rate variability (HRV). Subjective ratings of mental fatigue increased from pre to 0-min post in all-treatments, but not the documentary (p < 0.05). Subjective fatigue (VAS) remained higher (p < 0.05) than pretreatment values for 20-, 50-, and 60-min following the PVT, Stroop, and AX-CPT respectively. The cognitively demanding tasks had unclear effects on 3-min PVT, EEG, and HRV assessments. Tasks requiring response inhibition appear to induce fatigue for longer durations than a simple vigilance task. Simple VAS appear to be the most practical method for assessing mental fatigue.

Solanes, JE, Gracia, L, Muñoz-Benavent, P, Valls Miro, J, Perez-Vidal, C & Tornero, J 2019, 'Robust Hybrid Position-Force Control for Robotic Surface Polishing', Journal of Manufacturing Science and Engineering, vol. 141, no. 1.
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This work presents a hybrid position-force control of robots for surface polishing using task priority. The robot force control is designed using sliding mode ideas in order to benefit from its inherent robustness and low computational cost. In order to avoid the chattering drawback typically present in sliding mode control, several chattering-free controllers are evaluated and tested. A distinctive feature of the method is that the sliding mode force task is defined using not only equality constraints but also inequality constraints, which are satisfied using conventional and nonconventional sliding mode control, respectively. Moreover, a lower priority tracking controller is defined to follow the desired reference trajectory on the surface being polished. The applicability and the effectiveness of the proposed approach considering the mentioned chattering-free controllers are substantiated by experimental results using a redundant 7R manipulator.

Sopina, E, Chenoweth, L, Luckett, T, Agar, M, Luscombe, GM, Davidson, PM, Pond, CD, Phillips, J & Goodall, S 2019, 'Health-related quality of life in people with advanced dementia: a comparison of EQ-5D-5L and QUALID instruments', Quality of Life Research, vol. 28, no. 1, pp. 121-129.
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Assessing health-related quality of life (HRQOL) in people with advanced dementia is challenging but important for informed decision-making. Proxy measurement of this construct is difficult and is often rated lower than self-report. Accurate proxy rating of quality of life in dementia is related to identification of concepts important to the person themselves, as well as the sensitivity of the measures used. The main aim of this study was to compare the performance of two instruments-QUALID and EQ-5D-5L-on measuring HRQOL in people with advanced dementia.In a sub-study nested within a cluster-RCT we collected proxy(nurse)-completed EQ-5D-5L and QUALID measures at baseline, 3, 6, 9 and 12 months' follow-up for people with advanced dementia, residing in 20 nursing homes across Australia. Spearman's rank correlations, partial correlations and linear regressions were used to assess the relationship between the HRQOL instrument scores and their changes over time.The mean weight from 284 people for the EQ-5D-5L and QUALID at baseline were 0.004 (95% CI - 0.026, 0.033) and 24.98 (95% CI 24.13, 25.82), respectively. At 12 months' follow-up, 115 participants remained alive. EQ-5D-5L weights and QUALID scores at baseline and at follow-up were moderately correlated (r = - 0.437; p < 0.001 at 12 months). Changes within QUALID and EQ-5D-5L across the same follow-up periods were also correlated (r = - 0.266; p = 0.005). The regression analyses support these findings.Whilst these quality of life instruments demonstrated moderate correlation, the EQ-5D-5L does not appear to capture all aspects of quality of life that are relevant to people with advanced dementia and we cannot recommend the use of this instrument for use within this population. The QUALID appears to be a more suitable instrument for measuring HRQOL in people with severe dementia, but is not preference-based, which limits its application in economic evaluations of dementia care.

Stangenberg, S, Nguyen, LT, Chan, YL, Zaky, A, Pollock, CA, Chen, H & Saad, S 2019, 'Maternal L‐carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking', Clinical and Experimental Pharmacology and Physiology, vol. 46, no. 2, pp. 183-193.
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SummaryObjectivesEpidemiological and animal studies showed that L‐carnitine (LC) supplementation can ameliorate oxidative stress‐induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams during pregnancy. Exposure to an adverse intrauterine environment may lead to alteration in the epigenome, a mechanism by which adverse prenatal conditions increase the susceptibility to chronic disease later in life. The current study aimed to determine whether maternal SE induces epigenetic changes in the offspring's kidney are associated with renal underdevelopment, and the protective effect of maternal LC supplementation.MethodFemale Balb/c mice (7 weeks) were exposed to cigarette smoke (SE) or air (Sham) for 6 weeks prior to mating, during gestation and lactation. A subgroup of the SE dams received LC via drinking water (SE + LC, 1.5 mmol/L) throughout gestation and lactation. Male offspring were studied at postnatal day (P)1, P20, and 13 weeks.

Styrkarsdottir, U, Stefansson, OA, Gunnarsdottir, K, Thorleifsson, G, Lund, SH, Stefansdottir, L, Juliusson, K, Agustsdottir, AB, Zink, F, Halldorsson, GH, Ivarsdottir, EV, Benonisdottir, S, Jonsson, H, Gylfason, A, Norland, K, Trajanoska, K, Boer, CG, Southam, L, Leung, JCS, Tang, NLS, Kwok, TCY, Lee, JSW, Ho, SC, Byrjalsen, I, Center, JR, Lee, SH, Koh, J-M, Lohmander, LS, Ho-Pham, LT, Nguyen, TV, Eisman, JA, Woo, J, Leung, P-C, Loughlin, J, Zeggini, E, Christiansen, C, Rivadeneira, F, van Meurs, J, Uitterlinden, AG, Mogensen, B, Jonsson, H, Ingvarsson, T, Sigurdsson, G, Benediktsson, R, Sulem, P, Jonsdottir, I, Masson, G, Holm, H, Norddahl, GL, Thorsteinsdottir, U, Gudbjartsson, DF & Stefansson, K 2019, 'GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures', Nature Communications, vol. 10, no. 1.
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AbstractBone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10−42, β = −0.090) and confers risk of hip fracture (P = 1.0 × 10−8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.

Styrkarsdottir, U, Stefansson, OA, Gunnarsdottir, K, Thorleifsson, G, Lund, SH, Stefansdottir, L, Juliusson, K, Agustsdottir, AB, Zink, F, Halldorsson, GH, Ivarsdottir, EV, Benonisdottir, S, Jonsson, H, Gylfason, A, Norland, K, Trajanoska, K, Boer, CG, Southam, L, Leung, JCS, Tang, NLS, Kwok, TCY, Lee, JSW, Ho, SC, Byrjalsen, I, Center, JR, Lee, SH, Koh, J-M, Lohmander, LS, Ho-Pham, LT, Nguyen, TV, Eisman, JA, Woo, J, Leung, P-C, Loughlin, J, Zeggini, E, Christiansen, C, Rivadeneira, F, van Meurs, J, Uitterlinden, AG, Mogensen, B, Jonsson, H, Ingvarsson, T, Sigurdsson, G, Benediktsson, R, Sulem, P, Jonsdottir, I, Masson, G, Holm, H, Norddahl, GL, Thorsteinsdottir, U, Gudbjartsson, DF & Stefansson, K 2019, 'Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures', Nature Communications, vol. 10, no. 1.
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The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read ‘School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia’ and ‘St Vincent’s Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.’ This has now been corrected in both the PDF and HTML versions of the Article.

Sutton, SK, Cheung, BB, Massudi, H, Tan, O, Koach, J, Mayoh, C, Carter, DR & Marshall, GM 2019, 'Heterozygous loss of keratinocyte TRIM16 expression increases melanocytic cell lesions and lymph node metastasis', Journal of Cancer Research and Clinical Oncology, vol. 145, no. 9, pp. 2241-2250.
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© 2019, The Author(s). Purpose: The tripartite motif (TRIM)16 acts as a tumour suppressor in both squamous cell carcinoma (SCC) and melanoma. TRIM16 is known to be secreted by keratinocytes, but no studies have been reported yet to assess the relationship between TRIM16 keratinocyte expression and melanoma development. Methods: To study the role of TRIM16 in skin cancer development, we developed a keratinocyte TRIM16-specific knockout mouse model, and used the classical two-stage skin carcinogenesis challenge method, to assess the loss of keratinocyte TRIM16 on both papilloma, SCC and melanoma development in the skin after topical carcinogen treatment. Results: Heterozygous, but not homozygous, TRIM16 knockout mice exhibited an accelerated development of skin papillomas and melanomas, larger melanoma lesions and an increased potential for lymph node metastasis. Conclusion: This study provides the first evidence that keratinocyte loss of the putative melanoma tumour suppressor protein, TRIM16, enhances melanomagenesis. Our data also suggest that TRIM16 expression in keratinocytes is involved in cross talk between keratinocytes and melanocytes, and has a role in melanoma tumorigenesis.

Sweeney, CJ, De Abreu Lourenco, R, Hamid, AA & Buyse, M 2019, 'What Does Metastasis-Free Survival Actually Mean?', Journal of Clinical Oncology, vol. 37, no. 19, pp. 1679-1680.
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Tang, T, Liu, Y, Zhang, B, Su, B & Li, J 2019, 'Sketch distance-based clustering of chromosomes for large genome database compression', BMC Genomics, vol. 20, no. S10, pp. 978-978.
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AbstractBackgroundThe rapid development of Next-Generation Sequencing technologies enables sequencing genomes with low cost. The dramatically increasing amount of sequencing data raised crucial needs for efficient compression algorithms. Reference-based compression algorithms have exhibited outstanding performance on compressing single genomes. However, for the more challenging and more useful problem of compressing a large collection ofngenomes, straightforward application of these reference-based algorithms suffers a series of issues such as difficult reference selection and remarkable performance variation.ResultsWe propose an efficient clustering-based reference selection algorithm for reference-based compression within separate clusters of thengenomes. This method clusters the genomes into subsets of highly similar genomes using MinHash sketch distance, and uses the centroid sequence of each cluster as the reference genome for an outstanding reference-based compression of the remaining genomes in each cluster. A final reference is then selected from these reference genomes for the compression of the remaining reference genomes. Our method significantly improved the performance of the-state-of-art compression algorithms on large-scale human and rice genome databases containing thousands of genome sequences. The compression ratio gain can reach up to 20-30% in most cases for the datasets from NCBI, the 1000 Human Genomes Project and the 3000 Rice Genomes Project. The best improvement boosts the performance from 351.74 compression folds to 443.51 folds.ConclusionsThe compression ratio of reference-based compression on large scale genome datasets can be improved via reference selection by applying appropriate...

Tavakoli, J, Gascooke, J, Xie, N, Tang, BZ & Tang, Y 2019, 'Enlightening Freeze–Thaw Process of Physically Cross-Linked Poly(vinyl alcohol) Hydrogels by Aggregation-Induced Emission Fluorogens', ACS Applied Polymer Materials, vol. 1, no. 6, pp. 1390-1398.
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Tavakoli, J, Laisak, E, Gao, M & Tang, Y 2019, 'AIEgen quantitatively monitoring the release of Ca2+ during swelling and degradation process in alginate hydrogels', Materials Science and Engineering: C, vol. 104, pp. 109951-109951.
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© 2019 Elsevier B.V. Alginate-based hydrogels are extensively used for different biomedical applications. While the swelling and degradation of alginate-based hydrogels affect their structure-property relationship, many studies employed gravimetric analysis to characterize the swelling-degradation process. Accurate or not, this traditional method is difficult to be consistently performed with minimized errors, especially at the late stage of the process. For the first time, this study introduced a reliable, accurate and cost-effective method to minimize the human-sourced errors during repetitive measurement of swelling and degradation of alginate-based hydrogels based on Ca2+ specified aggregation-induced emission fluorogen technology. This study provides an approach for characterization of different properties of alginate-based tissue engineered scaffolds. The established relation between the changes in released Ca2+ into the swelling environment and its relative intensity identified the potential application of the proposed method for prediction of swelling and degradation behaviour in alginate-based hydrogels.

Tavakoli, J, Zhang, H-P, Tang, BZ & Tang, Y 2019, 'Aggregation-induced emission lights up the swelling process: a new technique for swelling characterisation of hydrogels', Materials Chemistry Frontiers, vol. 3, no. 4, pp. 664-667.
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The characterization of the swelling properties in hydrogels suffers uncertainty due to the limitations that occur during weight change measurement.

Thambar, PJ, Brown, DA & Sivabalan, P 2019, 'Managing systemic uncertainty: The role of industry-level management controls and hybrids', Accounting, Organizations and Society, vol. 77, pp. 101049-101049.
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© 2019 We study how multiple firms voluntarily design inter-firm mechanisms to manage industry-level systemic uncertainty. Facing a threat of systemic uncertainty that cannot be addressed by any one firm, we explain how the Australian cotton industry mobilised hybrids and boundary spanners to develop an industry-level solution at the inter-firm level. We apply resource dependence theory to extend Miller, Kurunmäki and O'Leary (2008), and identify a broader range of hybrid characteristics (novel, inter-firm, public/private and open source) than currently acknowledged in accounting studies. We use these characteristics to explain how hybrid organisational forms and hybrid control processes operate at the inter-firm level to develop and share a solution to systemic uncertainty, which are subsequently applied at the firm-level. Our findings also show how boundary spanners can operate with less tension in larger industry-level collaborations, explained using our resource dependence conceptualisation. This responds to Dekker's (2016) calls for more inter-firm research clarifying how controls operate beyond the firm.

Thompson, CJ, Fransen, J, Skorski, S, Smith, MR, Meyer, T, Barrett, S & Coutts, AJ 2019, 'Mental Fatigue in Football: Is it Time to Shift the Goalposts? An Evaluation of the Current Methodology', Sports Medicine, vol. 49, no. 2, pp. 177-183.
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© 2018, Springer Nature Switzerland AG. Research in football for a long time has focused on the physical nature of fatigue as opposed to its mental aspects. However, since 2016, six original articles have investigated the effects of induced mental fatigue in football on isolated physical, skill and decision-making performance tests, along with physical, technical and tactical performance outcomes in small-sided games. Whilst these studies have overall shown a negative impact of mental fatigue on task performance, this current opinion aims to critically examine the methodological approach to this problem, most notably the lack of ecological validity when inducing mental fatigue and the present approach to measuring mental fatigue using visual analogue scales (VAS). It is suggested that future research on mental fatigue in football may benefit from the use of surveys/interviews to understand the true cognitive demands of elite football players. Additionally, future research should aim to reduce the reliance on using VAS to measure mental fatigue as results from this tool may be confounded by several response biases. In conclusion, this article highlights the need for mentally fatiguing tasks that adequately represent football-associated mental fatigue and assessments of mental fatigue that minimise the confounding effect of response bias.

To, THM, Soo, WK, Lane, H, Khattak, A, Steer, C, Devitt, B, Dhillon, HM, Booms, A & Phillips, J 2019, 'Utilisation of geriatric assessment in oncology - a survey of Australian medical oncologists', Journal of Geriatric Oncology, vol. 10, no. 2, pp. 216-221.
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© 2018 Elsevier Inc. Introduction: Geriatric assessment (GA) is a multidimensional health assessment of the older person to evaluate their physical and cognitive function, comorbidities, nutrition, medications, psychological state, and social supports. GA may help oncologists optimise care for older patients with cancer. The aim of this study was to explore the views of Australian medical oncologists regarding the incorporation of geriatric screening tools, GA and collaboration with geriatricians into routine clinical practice. Methods: Members of the Medical Oncology Group of Australia were invited to complete an online survey that evaluated respondent demographics, practice characteristics, treatment decision-making factors, use of GA, and access to geriatricians. Results: Sixty-nine respondents identified comorbidities, polypharmacy, and poor functional status as the most frequent challenges in caring for older patients with cancer. Physical function, social supports and nutrition were the most frequent factors influencing treatment decision-making. The majority of respondents perceived value in GA and geriatrician review, although access was a barrier for referral. Such services would need to be responsive, providing reports within two weeks for the majority of respondents. Conclusion: Despite an emerging evidence base for the potential benefits of GA and collaboration with geriatricians, medical oncologists reported a lack of access but a desire to engage with these services.

Torres-Robles, A, Wiecek, E, Cutler, R, Drake, B, Benrimoj, SI, Fernandez-Llimos, F & Garcia-Cardenas, V 2019, 'Using Dispensing Data to Evaluate Adherence Implementation Rates in Community Pharmacy', Frontiers in Pharmacology, vol. 10, no. FEB, p. 130.
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Copyright © 2019 Torres-Robles, Wiecek, Cutler, Drake, Benrimoj, Fernandez-Llimos and Garcia-Cardenas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Background: Medication non-adherence remains a significant problem for the health care system with clinical, humanistic and economic impact. Dispensing data is a valuable and commonly utilized measure due accessibility in electronic health data. The purpose of this study was to analyze the changes on adherence implementation rates before and after a community pharmacist intervention integrated in usual real life practice, incorporating big data analysis techniques to evaluate Proportion of Days Covered (PDC) from pharmacy dispensing data. Methods: Retrospective observational study. A de-identified database of dispensing data from 20,335 patients (n = 11,257 on rosuvastatin, n = 6,797 on irbesartan, and n = 2,281 on desvenlafaxine) was analyzed. Included patients received a pharmacist-led medication adherence intervention and had dispensing records before and after the intervention. As a measure of adherence implementation, PDC was utilized. Analysis of the database was performed using SQL and Python. Results: Three months after the pharmacist intervention there was an increase on average PDC from 50.2% (SD: 30.1) to 66.9% (SD: 29.9) for rosuvastatin, from 50.8% (SD: 30.3) to 68% (SD: 29.3) for irbesartan and from 47.3% (SD: 28.4) to 66.3% (SD: 27.3) for desvenlafaxine. These rates declined over 12 months to 62.1% (SD: 32.0) for rosuvastatin, to 62.4% (SD: 32.5) for irbesartan and to 58.1% (SD: 31.1) for desvenla...

Tran, HV, Tran‐Le, PT & Nguyen, TV 2019, 'Treatment of vocal cord paralysis by autologous fat injection: Our experience with 41 patients', Clinical Otolaryngology, vol. 44, no. 1, pp. 76-80.
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Tribolet, R, Watsford, ML, Coutts, AJ, Smith, C & Fransen, J 2019, 'From entry to elite: The relative age effect in the Australian football talent pathway', Journal of Science and Medicine in Sport, vol. 22, no. 6, pp. 741-745.
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© 2018 Sports Medicine Australia Objectives: This study aimed to assess the first instance and prevalence of the Relative Age Effect (RAE) in the male Australian Football (AF) talent development pathway through to the Australian Football League (AFL). Design: Retrospective cross-sectional analysis. Methods: Birthdate distribution was accessed from an U10–U12 AF academy trial (n = 514), U13–U19 AF academy players (n = 408), AFL state, national and international combines (n = 2989), AFL Rising Star nominees (n = 50) and the top ten AFL Brownlow vote recipients (n = 50) between 2013–2017. Results: Chi-squared analysis showed significant overrepresentation to early born players in the selection year for both quartile and half-year compared to the previously known distribution at different stages of the talent pathway. Odds ratio demonstrated bias to players born in quartiles one and two of the selection year compared to players born in quartile four in every cohort examined. Conclusions: RAEs appear between ages 10–12 in the male AF development pathway and continue to senior professional competition. RAEs are amplified as the competition for positions increases and at points where selection cut-offs occur. Interestingly, players receiving votes for the AFL's best and fairest award were 12.6 times more likely to be born in the first half of the year. This may suggest a latent effect, which has long term benefits for relatively older players. Nonetheless, the RAE affects career progression in a male AF talent pathway.

Uddin, MB, Su, SW, Chen, W & Chow, CM 2019, 'Dynamic changes in electroencephalogram spectral power with varying apnea duration in older adults', Journal of Sleep Research, vol. 28, no. 6.
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AbstractSleep apnea elicits brain and physiological changes and its duration varies across the night. This study investigates the changes in the relative powers in electroencephalogram (EEG) frequency bands before and at apnea termination and as a function of apnea duration. The analysis was performed on 30 sleep records (375 apnea events) of older adults diagnosed with sleep apnea. Power spectral analysis centered on two 10‐s EEG epochs, before apnea termination (BAT) and after apnea termination (AAT), for each apnea event. The relative power changes in EEG frequency bands were compared with changes in apnea duration, defined as Short (between 10 and 20 s), Moderate (between 20 and 30 s) and Long (between 30 and 40 s). A significant reduction in EEG relative powers for lower frequency bands of alpha and sigma were observed for the Long compared to the Moderate and Short apnea duration groups at BAT, and reduction in relative theta, alpha and sigma powers for the Long compared to the Moderate and Short groups at AAT. The proportion of apnea events showed a significantly decreased trend with increased apnea duration for non‐rapid eye movement sleep but not rapid eye movement sleep. The proportion of central apnea events decreased with increased apnea duration, but not obstructive episodes. The findings suggest EEG arousal occurred both before and at apnea termination and these transient arousals were associated with a reduction in relative EEG powers of the low‐frequency bands: theta, alpha and sigma. The clinical implication is that these transient EEG arousals, without awakenings, are protective of sleep. Further studies with large datasets and different age groups are recommended.

Violi, JP, Facey, JA, Mitrovic, SM, Colville, A & Rodgers, KJ 2019, 'Production of β-methylamino-L-alanine (BMAA) and Its Isomers by Freshwater Diatoms', Toxins, vol. 11, no. 9, pp. 512-512.
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β-methylamino-L-alanine (BMAA) is a non-protein amino acid that has been implicated as a risk factor for motor neurone disease (MND). BMAA is produced by a wide range of cyanobacteria globally and by a small number of marine diatoms. BMAA is commonly found with two of its constitutional isomers: 2,4-diaminobutyric acid (2,4-DAB), and N-(2-aminoethyl)glycine (AEG). The isomer 2,4-DAB, like BMAA, has neurotoxic properties. While many studies have shown BMAA production by cyanobacteria, few studies have looked at other algal groups. Several studies have shown BMAA production by marine diatoms; however, there are no studies examining freshwater diatoms. This study aimed to determine if some freshwater diatoms produced BMAA, and which diatom taxa are capable of BMAA, 2,4-DAB and AEG production. Five axenic diatom cultures were established from river and lake sites across eastern Australia. Cultures were harvested during the stationary growth phase and intracellular amino acids were extracted. Using liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS), diatom extracts were analysed for the presence of both free and protein-associated BMAA, 2,4-DAB and AEG. Of the five diatom cultures analysed, four were found to have detectable BMAA and AEG, while 2,4-DAB was found in all cultures. These results show that BMAA production by diatoms is not confined to marine genera and that the prevalence of these non-protein amino acids in Australian freshwater environments cannot be solely attributed to cyanobacteria.

Violi, JP, Mitrovic, SM, Colville, A, Main, BJ & Rodgers, KJ 2019, 'Prevalence of β-methylamino-L-alanine (BMAA) and its isomers in freshwater cyanobacteria isolated from eastern Australia', Ecotoxicology and Environmental Safety, vol. 172, pp. 72-81.
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© 2019 Elsevier Inc. Environmental exposure to the amino acid β-methylamino-L-alanine (BMAA) was linked to the high incidence of neurodegenerative disease first reported on the island of Guam in the 1940s and has more recently been implicated in an increased incidence of amyotrophic lateral sclerosis (ALS) in parts of the USA. BMAA has been shown to be produced by a range of cyanobacteria and some marine diatoms and dinoflagellates in different parts of the world. BMAA is commonly found with two of its constitutional isomers: 2,4- diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl) glycine (AEG). These isomers are thought to be co-produced by the same organisms that produce BMAA and MS/MS analysis following LC separation can add an additional level of specificity over LC-FL. Although the presence of BMAA and 2,4-DAB in surface scum samples from several sites in Australia has been reported, which Australian cyanobacterial species are capable of BMAA, 2,4-DAB and AEG production remains unknown. The aims of the present studies were to identify some of the cyanobacterial genera or species that can produce BMAA, 2,4-DAB and AEG in freshwater cyanobacteria blooms in eastern Australia. Eleven freshwater sites were sampled and from these, 19 single-species cyanobacterial cultures were established. Amino acids were extracted from cyanobacterial cultures and analysed using liquid chromatography-tandem mass spectrometry. BMAA was detected in 17 of the 19 isolates, 2,4-DAB was detected in all isolates, and AEG was detected in 18 of the 19 isolates, showing the prevalence of these amino acids in Australian freshwater cyanobacteria. Concentrations of all three isomers in Australian cyanobacteria were generally higher than the concentrations reported elsewhere. This study confirmed the presence of BMAA and its isomers in cyanobacteria isolated from eastern Australian freshwater systems, and determined which Australian cyanobacterial genera or species were capable of pr...

Virdun, C, Luckett, T, Gilmore, I, Brassil, M, Lilian, R, Lorenz, K & Phillips, J 2019, 'Involving consumers with palliative care needs and their families in research: A case study', Collegian, vol. 26, no. 6, pp. 645-650.
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© 2019 Australian College of Nursing Ltd Background: There are significant policy imperatives to involve consumers at the outset of and throughout research. How best to achieve this in an authentic and meaningful way is elusive, particularly within the palliative care population. Aim: To determine how best to engage people with palliative care needs and their families in co-designing a qualitative study to better understand how to improve care of the dying in the acute care setting. Methods: A case study design informed this work, informed by pre-determined research questions that focused on consumers advising on participant experience within the research, rather than research methodology per se. Findings: Eleven consumers contributed across five panel meetings. Analysis of documented feedback led to four key areas of protocol change: Getting the language in the recruitment materials and information and consent forms right; Developing a feasible and acceptable recruitment strategy; Opportunities to more clearly articulate the explicit value of this research for patients and families; Support strategies for participants. Discussion: Authentic consumer engagement requires time and effort; however, the outcomes are well worth the invested time and energy. Key foci outlined within this case study to enhance authenticity included: collaboration; preferencing the consumer voice; adequate preparation to support consumer engagement; and openness to all feedback provided. Conclusion: Co-designing research with consumers enabled the outcome to be feasible for implementation, without any modifications required. Ensuring relevance and consumer-centredness for the expanding palliative care evidence base is essential and can only be achieved through meaningful partnerships with consumer representatives.

Vo, TT, Luong, NT & Hoang, D 2019, 'MLAMAN: a novel multi-level authentication model and protocol for preventing wormhole attack in mobile ad hoc network', Wireless Networks, vol. 25, no. 7, pp. 4115-4132.
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Vuckovic, S, Bryant, C, Marsh-Wakefield, F, Kruzins, A, McGuire, H, Yang, S, Fazekas de St. Groth, B, Nassif, N, Byrne, SN, Gibson, J, Brown, C, Larsen, S, McCulloch, D, Boyle, R, Clark, G, Joshua, D & Ho, PJ 2019, 'Activated and Bone-marrow Resident Treg Alterations Underlie Malignant Transformation from MGUS to Multiple Myeloma', Clinical Lymphoma Myeloma and Leukemia, vol. 19, no. 10, pp. e100-e100.
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Wang, J, Tavakoli, J & Tang, Y 2019, 'Bacterial cellulose production, properties and applications with different culture methods – A review', Carbohydrate Polymers, vol. 219, pp. 63-76.
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© 2019 Elsevier Ltd Bacterial cellulose (BC) is an organic compound produced by certain types of bacteria. In natural habitats, the majority of bacteria synthesize extracellular polysaccharides, such as cellulose, which form protective envelopes around the cells. Many methods are currently being investigated to enhance cellulose growth. The various celluloses produced by different bacteria possess different morphologies, structures, properties, and applications. However, the literature lacks a comprehensive review of the different methods of BC production, which are critical to BC properties and their final applications. The aims of this review are to provide an overview of the production of BC from different culture methods, to analyze the characteristics of particular BC productions, to indicate existing problems associated with different methods, and to choose suitable culture approaches for BC applications in different fields. The main goals for future studies have also been discussed here.

Winter, M, Cai, Z, Winkler, K, Georgiou, K, Inglis, D, Lavranos, T, Rezaei, M, Warkiani, M & Thierry, B 2019, 'Circulating tumour cell RNA characterisation from colorectal cancer patient blood after inertial microfluidic enrichment', MethodsX, vol. 6, pp. 1512-1520.
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© 2019 The Authors The detection and molecular analysis of circulating tumour cells (CTCs) potentially provides a significant insight to the characterisation of disease, stage of progression and therapeutic options for cancer patients. Following on from the protocol by Warkiani et al. 2016, which describes a method of enriching CTCs from cancer patient blood with inertial microfluidics, we describe a method to measure the CTC RNA expression in the enriched fraction using droplet digital PCR and compare transcript detection with and without RNA pre-amplification. • Inertial microfluidics combined with droplet digital PCR is advantageous as it allows for CTC enrichment and subsequent RNA analysis from patient blood. This allows for patient tumour analysis with increased sensitivity and precision compared to quantitative Real Time PCR and enables the direct quantification of nucleic acids without the need for tumour biopsy. • This method demonstrates an efficient approach providing important insights into the analysis of colorectal cancer patients’ CTCs using a specific gene subset or biomarkers, an approach that may be tailored to tumour type or expanded to larger panels.

Wood, LG, Li, Q, Scott, HA, Rutting, S, Berthon, BS, Gibson, PG, Hansbro, PM, Williams, E, Horvat, J, Simpson, JL, Young, P, Oliver, BG & Baines, KJ 2019, 'Saturated fatty acids, obesity, and the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome in asthmatic patients', Journal of Allergy and Clinical Immunology, vol. 143, no. 1, pp. 305-315.
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© 2018 American Academy of Allergy, Asthma & Immunology Background: Both obesity and high dietary fat intake activate the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome. Objective: We aimed to examine NLRP3 inflammasome activity in the airways of obese asthmatic patients after macronutrient overload and in immune cells challenged by inflammasome triggers. Methods: Study 1 was a cross-sectional observational study of nonobese (n = 51) and obese (n = 76) asthmatic adults. Study 2 was a randomized, crossover, acute feeding study in 23 asthmatic adults (n = 12 nonobese and n = 11 obese subjects). Subjects consumed 3 isocaloric meals on 3 separate occasions (ie, saturated fatty acid, n-6 polyunsaturated fatty acid, and carbohydrate) and were assessed at 0 and 4 hours. For Studies 1 and 2, airway inflammation was measured based on sputum differential cell counts, IL-1β protein levels (ELISA), and sputum cell gene expression (Nanostring nCounter). In Study 3 peripheral blood neutrophils and monocytes were isolated by using Ficoll density gradient and magnetic bead separation and incubated with or without palmitic acid, LPS, or TNF-α for 24 hours, and IL-1β release was measured (ELISA). Results: In Study 1 NLRP3 and nucleotide oligomerization domain 1 (NOD1) gene expression was upregulated, and sputum IL-1β protein levels were greater in obese versus nonobese asthmatic patients. In Study 2 the saturated fatty acid meal led to increases in sputum neutrophil percentages and sputum cell gene expression of Toll-like receptor 4 (TLR4) and NLRP3 at 4 hours in nonobese asthmatic patients. In Study 3 neutrophils and monocytes released IL-1β when challenged with a combination of palmitic acid and LPS or TNF-α. Conclusion: The NLRP3 inflammasome is a potential therapeutic target in asthmatic patients. Behavioral interventions that reduce fatty acid exposure, such as weight loss and dietary saturated fat restriction, warrant further exploration.

Wu, Y, Liu, T, Ling, S, Szymanski, J, Zhang, W & Su, S 2019, 'Air Quality Monitoring for Vulnerable Groups in Residential Environments Using a Multiple Hazard Gas Detector', Sensors, vol. 19, no. 2, pp. 362-362.
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This paper presents a smart “e-nose” device to monitor indoor hazardous air. Indoor hazardous odor is a threat for seniors, infants, children, pregnant women, disabled residents, and patients. To overcome the limitations of using existing non-intelligent, slow-responding, deficient gas sensors, we propose a novel artificial-intelligent-based multiple hazard gas detector (MHGD) system that is mounted on a motor vehicle-based robot which can be remotely controlled. First, we optimized the sensor array for the classification of three hazardous gases, including cigarette smoke, inflammable ethanol, and off-flavor from spoiled food, using an e-nose with a mixing chamber. The mixing chamber can prevent the impact of environmental changes. We compared the classification results of all combinations of sensors, and selected the one with the highest accuracy (98.88%) as the optimal sensor array for the MHGD. The optimal sensor array was then mounted on the MHGD to detect and classify the target gases without a mixing chamber but in a controlled environment. Finally, we tested the MHGD under these conditions, and achieved an acceptable accuracy (70.00%).

Xu, X, Parker, D & Inglis, S 2019, 'The Longitudinal Association Between Food Groups, Memory Loss and Comorbidity of Heart Disease in Older People: Results from the 45 and Up Study', Heart, Lung and Circulation, vol. 28, pp. S141-S142.
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Xu, X, Parker, D, Inglis, SC & Byles, J 2019, 'Can regular long-term breakfast cereals consumption benefits lower cardiovascular diseases and diabetes risk? A longitudinal population-based study', Annals of Epidemiology, vol. 37, pp. 43-50.e3.
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PURPOSE:Studies indicate breakfast cereals may reduce the risk of overweight, cardiovascular diseases, and diabetes, but a limited number of longitudinal studies have explored these relationships, indicating the need for further assessment. METHODS:We used 45 and Up Study data to examine the longitudinal association between breakfast cereals (and different categories of cereals) and heart disease, stroke, and diabetes. Dietary consumption was assessed by a short food frequency questionnaire. Diagnosed heart disease, stroke, and diabetes were self-reported. Generalized estimating equation models were used to examine the longitudinal associations. RESULTS:Of a total of 142,503 participants (aged 45 years and older), people in the older age group (aged 80 or older) had significantly higher breakfast cereal consumption (P < .001) than those in the younger age group (aged 45-64 years). A significantly inverse association was found between breakfast muesli and heart disease, stroke, and diabetes across all age groups. Associations between other categories of breakfast cereals (biscuit, bran, and oat cereals) and these three diseases differed by age groups. A positive association was found between oat cereals and diabetes for people in the younger age groups (aged 80 years and younger), but not for people in the older age group (aged 80 years and older). CONCLUSIONS:The benefit of breakfast muesli consumption was highlighted in prevention of these three diseases. The result suggests that age-specific dietary guidelines, with a particular focus on the types of breakfast cereals consumption in prevention of chronic diseases for older people need to be developed.

Yee, J, Davis, GM, Hackett, D, Beith, JM, Wilcken, N, Currow, D, Emery, J, Phillips, J, Martin, A, Hui, R, Harrison, M, Segelov, E & Kilbreath, SL 2019, 'Physical Activity for Symptom Management in Women With Metastatic Breast Cancer: A Randomized Feasibility Trial on Physical Activity and Breast Metastases', Journal of Pain and Symptom Management, vol. 58, no. 6, pp. 929-939.
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Zakarya, R, Adcock, I & Oliver, BG 2019, 'Epigenetic impacts of maternal tobacco and e-vapour exposure on the offspring lung', Clinical Epigenetics, vol. 11, no. 1.
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© 2019 The Author(s). In utero exposure to tobacco products, whether maternal or environmental, have harmful effects on first neonatal and later adult respiratory outcomes. These effects have been shown to persist across subsequent generations, regardless of the offsprings' smoking habits. Established epigenetic modifications induced by in utero exposure are postulated as the mechanism underlying the inherited poor respiratory outcomes. As e-cigarette use is on the rise, their potential to induce similar functional respiratory deficits underpinned by an alteration in the foetal epigenome needs to be explored. This review will focus on the functional and epigenetic impact of in utero exposure to maternal cigarette smoke, maternal environmental tobacco smoke, environmental tobacco smoke and e-cigarette vapour on foetal respiratory outcomes.

Zhang, B, Li, J, Quan, L, Chen, Y & Lü, Q 2019, 'Sequence-based prediction of protein-protein interaction sites by simplified long short-term memory network', Neurocomputing, vol. 357, pp. 86-100.
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© 2019 Elsevier B.V. Proteins often interact with each other and form protein complexes to carry out various biochemical activities. Knowledge of the interaction sites is helpful for understanding disease mechanisms and drug design. Accurate prediction of the interaction sites from protein sequences is still a challenging task and severe imbalance data also decreased the performance of computational methods. In this study, we propose to use a deep learning method for improving the imbalanced prediction of protein interaction sites. We develop a new simplified long short-term memory (SLSTM) network to implement a deep learning architecture (named DLPred). To deal with the imbalanced classification in the deep learning model, we explore three new ideas. First, our collection of the training data is to construct a set of protein sequences, instead of a set of just single residues, to retain the entire sequential completeness of each protein. Second, a new penalization factor is appended to the loss function such that the penalization to the non-interaction site loss can be effectively enhanced. Third, multi-task learning of interaction sites and residue solvent accessibility prediction are used for correcting the preference of the prediction model on the non-interaction sites. Our model is evaluated on three public datasets: Dset186, Dtestset72 and PDBtestset164. Compared with current state-of-the-art methods, DLPred is able to significantly improve the predictive accuracies and AUC values while improving the F-measure. The training dataset, test datasets, a standalone version of DLPred and online service are available at http://qianglab.scst.suda.edu.cn/dlp/.

Zhang, H-P, Han, W, Tavakoli, J, Zhang, Y-P, Lin, X, Lu, X, Ma, Y & Tang, Y 2019, 'Understanding interfacial interactions of polydopamine and glass fiber and their enhancement mechanisms in epoxy-based laminates', Composites Part A: Applied Science and Manufacturing, vol. 116, pp. 62-71.
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Interfacial behavior greatly affects the bulk mechanical performance of fiber reinforced polymer laminates. In this study, polydopamine modified glass fiber was used to fabricate short glass fiber reinforced polymer (GFRP) laminates. The interactions between glass fiber and polydopamine were studied experimentally and theoretically by X-ray photoelectron spectroscopy (XPS) and density functional calculation respectively. Theoretical study clearly demonstrated that electronic interactions existed between polydopamine and glass fiber, indicating the hydrogen bonds/chemical interactions between them that were also demonstrated by XPS results. The enhanced interfacial interaction significantly benefited GFRP laminates, as demonstrated by various mechanical characterizations such as single fiber pull-out and Mode I interlaminar fracture toughness tests. Combining the theoretical and experimental studies indicated that polydopamine modification of glass fiber could be an easy and effective way to significantly improve the interfacial interactions between glass fiber and matrix and enhance the mechanical properties of GFRP laminates.

Zhang, W, Liu, T, Ye, L, Ueland, M, Forbes, SL & Su, SW 2019, 'A novel data pre-processing method for odour detection and identification system', Sensors and Actuators A: Physical, vol. 287, pp. 113-120.
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© 2018 Elsevier B.V. This paper presents a novel electronic nose (E-nose) data pre-processing method, based on a recently developed non-parametric kernel-based modelling (KBM) approach. The proposed method is tested by an automated odour detection and classification system, named “NOS.E” developed by the NOS.E team in University of Technology Sydney. Experimental results show that when extracting the derivative-related features from signals collected by the NOS.E, the proposed non-parametric KBM odour data pre-processing method achieves more reliable and stable pre-processing results comparing with other pre-processing methods such as wavelet package correlation filter (WPCF), mean filter (MF), polynomial curve fitting (PCF) and locally weighted regression (LWR). Based on these derivative-related features, the NOS.E can achieve a 96.23% accuracy of classification with the popular Support Vector Machine (SVM) classifier.

Zhao, Z, Peng, H, Zhang, X, Zheng, Y, Chen, F, Fang, L & Li, J 2019, 'Identification of lung cancer gene markers through kernel maximum mean discrepancy and information entropy', BMC Medical Genomics, vol. 12, no. S8.
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AbstractBackgroundThe early diagnosis of lung cancer has been a critical problem in clinical practice for a long time and identifying differentially expressed gene as disease marker is a promising solution. However, the most existing gene differential expression analysis (DEA) methods have two main drawbacks: First, these methods are based on fixed statistical hypotheses and not always effective; Second, these methods can not identify a certain expression level boundary when there is no obvious expression level gap between control and experiment groups.MethodsThis paper proposed a novel approach to identify marker genes and gene expression level boundary for lung cancer. By calculating a kernel maximum mean discrepancy, our method can evaluate the expression differences between normal, normal adjacent to tumor (NAT) and tumor samples. For the potential marker genes, the expression level boundaries among different groups are defined with the information entropy method.ResultsCompared with two conventional methods t-test and fold change, the top average ranked genes selected by our method can achieve better performance under all metrics in the 10-fold cross-validation. Then GO and KEGG enrichment analysis are conducted to explore the biological function of the top 100 ranked genes. At last, we choose the top 10 average ranked genes as lung cancer markers and their expression boundaries are calculated and reported.ConclusionThe proposed approach is effective to identify gene markers for lung cancer diagnosis. It is not only more accurate than conventional DEA methods but also provides a reliable method to identify the gene expression level boundaries.

Zheng, Y, Peng, H, Ghosh, S, Lan, C & Li, J 2019, 'Inverse similarity and reliable negative samples for drug side-effect prediction', BMC Bioinformatics, vol. 19, no. S13, pp. 554-554.
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© 2019 The Author(s). Background: In silico prediction of potential drug side-effects is of crucial importance for drug development, since wet experimental identification of drug side-effects is expensive and time-consuming. Existing computational methods mainly focus on leveraging validated drug side-effect relations for the prediction. The performance is severely impeded by the lack of reliable negative training data. Thus, a method to select reliable negative samples becomes vital in the performance improvement. Methods: Most of the existing computational prediction methods are essentially based on the assumption that similar drugs are inclined to share the same side-effects, which has given rise to remarkable performance. It is also rational to assume an inverse proposition that dissimilar drugs are less likely to share the same side-effects. Based on this inverse similarity hypothesis, we proposed a novel method to select highly-reliable negative samples for side-effect prediction. The first step of our method is to build a drug similarity integration framework to measure the similarity between drugs from different perspectives. This step integrates drug chemical structures, drug target proteins, drug substituents, and drug therapeutic information as features into a unified framework. Then, a similarity score between each candidate negative drug and validated positive drugs is calculated using the similarity integration framework. Those candidate negative drugs with lower similarity scores are preferentially selected as negative samples. Finally, both the validated positive drugs and the selected highly-reliable negative samples are used for predictions. Results: The performance of the proposed method was evaluated on simulative side-effect prediction of 917 DrugBank drugs, comparing with four machine-learning algorithms. Extensive experiments show that the drug similarity integration framework has superior capability in capturing drug features, ac...

Zheng, Y, Peng, H, Zhang, X, Zhao, Z, Gao, X & Li, J 2019, 'DDI-PULearn: a positive-unlabeled learning method for large-scale prediction of drug-drug interactions', BMC Bioinformatics, vol. 20, no. S19.
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AbstractBackgroundDrug-drug interactions (DDIs) are a major concern in patients’ medication. It’s unfeasible to identify all potential DDIs using experimental methods which are time-consuming and expensive. Computational methods provide an effective strategy, however, facing challenges due to the lack of experimentally verified negative samples.ResultsTo address this problem, we propose a novel positive-unlabeled learning method named DDI-PULearn for large-scale drug-drug-interaction predictions. DDI-PULearn first generates seeds of reliable negatives via OCSVM (one-class support vector machine) under a high-recall constraint and via the cosine-similarity based KNN (k-nearest neighbors) as well. Then trained with all the labeled positives (i.e., the validated DDIs) and the generated seed negatives, DDI-PULearn employs an iterative SVM to identify a set of entire reliable negatives from the unlabeled samples (i.e., the unobserved DDIs). Following that, DDI-PULearn represents all the labeled positives and the identified negatives as vectors of abundant drug properties by a similarity-based method. Finally, DDI-PULearn transforms these vectors into a lower-dimensional space via PCA (principal component analysis) and utilizes the compressed vectors as input for binary classifications. The performance of DDI-PULearn is evaluated on simulative prediction for 149,878 possible interactions between 548 drugs, comparing with two baseline methods and five state-of-the-art methods. Related experiment results show that the proposed method for the representation of DDIs characterizes them accurately. DDI-PULearn achieves superior performance owing to the identified reliable negatives, outperforming all other methods significantly. In addition, the predicted novel DDIs suggest that DDI-PULearn is capable to identify novel DDIs.

Zheng, Y, Peng, H, Zhang, X, Zhao, Z, Gao, X & Li, J 2019, 'Old drug repositioning and new drug discovery through similarity learning from drug-target joint feature spaces', BMC Bioinformatics, vol. 20, no. S23, p. 605.
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AbstractBackgroundDetection of new drug-target interactions by computational algorithms is of crucial value to both old drug repositioning and new drug discovery. Existing machine-learning methods rely only on experimentally validated drug-target interactions (i.e., positive samples) for the predictions. Their performance is severely impeded by the lack of reliable negative samples.ResultsWe propose a method to construct highly-reliable negative samples for drug target prediction by a pairwise drug-target similarity measurement and OCSVM with a high-recall constraint. On one hand, we measure the pairwise similarity between every two drug-target interactions by combining the chemical similarity between their drugs and the Gene Ontology-based similarity between their targets. Then we calculate the accumulative similarity with all known drug-target interactions for each unobserved drug-target interaction. On the other hand, we obtain the signed distance from OCSVM learned from the known interactions with high recall (≥0.95) for each unobserved drug-target interaction. After normalizing all accumulative similarities and signed distances to the range [0,1], we compute the score for each unobserved drug-target interaction via averaging its accumulative similarity and signed distance. Unobserved interactions with lower scores are preferentially served as reliable negative samples for the classification algorithms. The performance of the proposed method is evaluated on the interaction data between 1094 drugs and 1556 target proteins. Extensive comparison experiments using four classical classifiers and one domain predictive method demonstrate the superior performance of the proposed method. A better decision boundary has been learned from the constructed reliable negative samples.Conc...

Abdollahi, M, Gao, X, Mei, Y, Ghosh, S & Li, J 1970, 'An Ontology-based Two-Stage Approach to Medical Text Classification with Feature Selection by Particle Swarm Optimisation', 2019 IEEE Congress on Evolutionary Computation (CEC), 2019 IEEE Congress on Evolutionary Computation (CEC), IEEE, New Zealand, pp. 119-126.
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© 2019 IEEE. Document classification (DC) is the task of assigning pre-defined labels to unseen documents by utilizing a model trained on the available labeled documents. DC has attracted much attention in medical fields recently because many issues can be formulated as a classification problem. It can assist doctors in decision making and correct decisions can reduce the medical expenses. Medical documents have special attributes that distinguish them from other texts and make them difficult to analyze. For example, many acronyms and abbreviations, and short expressions make it more challenging to extract information. The classification accuracy of the current medical DC methods is not satisfactory. The goal of this work is to enhance the input feature sets of the DC method to improve the accuracy. To approach this goal, a novel two-stage approach is proposed. In the first stage, a domain-specific dictionary, namely the Unified Medical Language System (UMLS), is employed to extract the key features belonging to the most relevant concepts such as diseases or symptoms. In the second stage, PSO is applied to select more related features from the extracted features in the first stage. The performance of the proposed approach is evaluated on the 2010 Informatics for Integrating Biology and the Bedside (i2b2) data set which is a widely used medical text dataset. The experimental results show substantial improvement by the proposed method on the accuracy of classification.

Abdollahi, M, Gao, X, Mei, Y, Ghosh, S & Li, J 1970, 'Stratifying Risk of Coronary Artery Disease Using Discriminative Knowledge-Guided Medical Concept Pairings from Clinical Notes', PRICAI 2019: Trends in Artificial Intelligence, Pacific Rim International Conference on Artificial Intelligence, Springer International Publishing, Cuvu, Yanuca Island, Fiji, pp. 457-473.
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© 2019, Springer Nature Switzerland AG. Document classification (DC) is one of the broadly investigated natural language processing tasks. Medical document classification can support doctors in making decision and improve medical services. Since the data in document classification often appear in raw form such as medical discharge notes, extracting meaningful information to use as features is a challenging task. There are many specialized words and expressions in medical documents which make them more challenging to analyze. The classification accuracy of available methods in medical field is not good enough. This work aims to improve the quality of the input feature sets to increase the accuracy. A new three-stage approach is proposed. In the first stage, the Unified Medical Language System (UMLS) which is a medical-specific dictionary is used to extract the meaningful phrases by considering disease or symptom concepts. In the second stage, all the possible pairs of the extracted concepts are created as new features. In the third stage, Particle Swarm Optimisation (PSO) is employed to select features from the extracted and constructed features in the previous stages. The experimental results show that the proposed three-stage method achieved substantial improvement over the existing medical DC approaches.

Alanazi, F, Gay, V & Alturki, R 1970, 'Tag Based Recommendation Systems for Tourism in Saudi Arabia', VISION 2025: EDUCATION EXCELLENCE AND MANAGEMENT OF INNOVATIONS THROUGH SUSTAINABLE ECONOMIC COMPETITIVE ADVANTAGE, 34th International-Business-Information-Management-Association (IBIMA) Conference, INT BUSINESS INFORMATION MANAGEMENT ASSOC-IBIMA, Madrid, SPAIN, pp. 6492-6500.

Alarkawi, D, Bliuc, D, Tran, T, Ahmed, LA, Emaus, N, Nguyen, TV, Eisman, JA & Center, JR 1970, 'IMPACT OF OSTEOPOROTIC FRACTURE TYPE AND SUBSEQUENT FRACTURE ON MORTALITY IN TROMSO, NORWAY', OSTEOPOROSIS INTERNATIONAL, IOF-Regional 7th Asia-Pacific Osteoporosis Conference, SPRINGER LONDON LTD, Sydney, AUSTRALIA, pp. S105-S106.

Ali, AR, Budka, M & Gabrys, B 1970, 'A Meta-Reinforcement Learning Approach to Optimize Parameters and Hyper-parameters Simultaneously', PRICAI 2019: Trends in Artificial Intelligence, Pacific Rim International Conference on Artificial Intelligence, Springer International Publishing, Yanuca Island, Fiji,, pp. 93-106.
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© 2019, Springer Nature Switzerland AG. In the last few years, we have witnessed a resurgence of interest in neural networks. The state-of-the-art deep neural network architectures are however challenging to design from scratch and requiring computationally costly empirical evaluations. Hence, there has been a lot of research effort dedicated to effective utilisation and adaptation of previously proposed architectures either by using transfer learning or by modifying the original architecture. The ultimate goal of designing a network architecture is to achieve the best possible accuracy for a given task or group of related tasks. Although there have been some efforts to automate network architecture design process, most of the existing solutions are still very computationally intensive. This work presents a framework to automatically find a good set of hyper-parameters resulting in reasonably good accuracy, which at the same time is less computationally expensive than the existing approaches. The idea presented here is to frame the hyper-parameter selection and tuning within the reinforcement learning regime. Thus, the parameters of a meta-learner, RNN, and hyper-parameters of the target network are tuned simultaneously. Our meta-learner is being updated using policy network and simultaneously generates a tuple of hyper-parameters which are utilized by another network. The network is trained on a given task for a number of steps and produces validation accuracy whose delta is used as reward. The reward along with the state of the network, comprising statistics of network’s final layer outcome and training loss, are fed back to the meta-learner which in turn generates a tuned tuple of hyper-parameters for the next time-step. Therefore, the effectiveness of a recommended tuple can be tested very quickly rather than waiting for the network to converge. This approach produces accuracy close to the state-of-the-art approach and is found to be comparatively l...

Ali, AR, Budka, M & Gabrys, B 1970, 'Towards Meta-learning of Deep Architectures for Efficient Domain Adaptation', PRICAI 2019: Trends in Artificial Intelligence, Pacific Rim International Conference on Artificial Intelligence, Springer International Publishing, Yanuca Island, Fiji., pp. 66-79.
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© 2019, Springer Nature Switzerland AG. This paper proposes an efficient domain adaption approach using deep learning along with transfer and meta-level learning. The objective is to identify how many blocks (i.e. groups of consecutive layers) of a pre-trained image classification network need to be fine-tuned based on the characteristics of the new task. In order to investigate it, a number of experiments have been conducted using different pre-trained networks and image datasets. The networks were fine-tuned, starting from the blocks containing the output layers and progressively moving towards the input layer, on various tasks with characteristics different from the original task. The amount of fine-tuning of a pre-trained network (i.e. the number of top layers requiring adaptation) is usually dependent on the complexity, size, and domain similarity of the original and new tasks. Considering these characteristics, a question arises of how many blocks of the network need to be fine-tuned to get maximum possible accuracy? Which of a number of available pre-trained networks require fine-tuning of the minimum number of blocks to achieve this accuracy? The experiments, that involve three network architectures each divided into 10 blocks on average and five datasets, empirically confirm the intuition that there exists a relationship between the similarity of the original and new tasks and the depth of network needed to fine-tune in order to achieve accuracy comparable with that of a model trained from scratch. Further analysis shows that the fine-tuning of the final top blocks of the network, which represent the high-level features, is sufficient in most of the cases. Moreover, we have empirically verified that less similar tasks require fine-tuning of deeper portions of the network, which however is still better than training a network from scratch.

Alturki, R & Gay, V 1970, 'Augmented and virtual reality in mobile fitness applications: A survey', EAI International Conference on Future Intelligent Vehicular Technologies, EAI International Conference on Future Intelligent Vehicular Technologies, ISLAMABAD, PAKISTAN, pp. 67-75.
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Obesity is a major issue around the world. It is the main reason for several chronic diseases. Obesity can be stopped by encouraging people to do physical activities and making behaviour intervention regarding lifestyle. Mobile fitness apps are emerging because of the unique features that are provided. They are seen as a vital tool to motivate people suffering from obesity to perform physical activities and make behaviour intervention regarding health and fitness. Augmented reality (AR) and virtual reality (VR) technologies have been used successfully in different kinds of mobile apps. This paper presents a systematic review of some of the most recent AG and VR researches in mobile apps. It discusses the main findings of applying both technologies in different fields of mobile apps. Based on this systematic review, a fitness mobile app for obese individuals that consider both AR and VR technology will be developed.

Alturki, R & Gay, V 1970, 'Usability attributes for mobile applications: A systematic review', EAI International Conference on Future Intelligent Vehicular Technologies, EAI International Conference on Future Intelligent Vehicular Technologies, Islamabad, Pakistan, pp. 53-62.
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The usability of mobile applications (apps) is an emerging area of research because of the increasing use of mobile devices around the world. App development is challenging because each application has its own purpose, and each individual user has different needs and expectations from the apps. There are various apps available for each purpose, and the success of the application depends on its usefulness. This paper presents a systematic review of some of the most contemporary apps and highlights their usability attributes. It discusses usability models, frameworks and guidelines outlined in previous research for designing apps with enhanced usability characteristics. Based on this research, comprehensive guidelines for mobile apps’ usability can then be provided.

Al-Zu'bi, MM, Mohan, AS & Ling, SSH 1970, 'Influence of Tissue Anisotropy on Molecular Communication.', EMBC, the 41st International Engineering in Medicine and Biology Conference, IEEE, Germany, pp. 2921-2924.
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Many biological tissues inside the human body exhibit highly anisotropic diffusion properties; for example, tissues of the nervous system and white matter in the brain. Here, we present an improved molecular communication model by introducing the tissue anisotropy to model diffusive molecular channel for nanomachine communications. We present a stochastic particle-based simulation model for molecular communication in three-dimensional (3D) anisotropic diffusive biological microenvironments and validate with analytical expressions. We also derive expressions for peak amplitude and peak time for the received molecular signal. The results demonstrate that the channel impulse response in anisotropic biological media depend significantly on the diffusion tensor as well as on the locations of the nanomachines.

Argha, A, Su, SW, Liu, Y & Celler, BG 1970, 'Control Allocation Based Sliding Mode Fault Tolerant Control', 2019 American Control Conference (ACC), 2019 American Control Conference (ACC), IEEE, Philadelphia, PA, USA, pp. 3752-3757.
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© 2019 American Automatic Control Council. This paper describes a novel fault tolerant control using robust sliding mode control strategy. This scheme can also be employed as actuator redundancy management for over-actuated uncertain linear systems. In contrast to many existing methods in the literature that assume the control input matrix is not of full rank such that it can be factorised into two matrices, this scheme can be applied to systems whose control input matrix has full rank. The so-called virtual control, in this scheme, is designed to be robust against uncertainties emanating from visibility of the control allocator to the controller and imperfection in the estimated effectiveness gain. Then using a static real-time control allocator, the obtained virtual control signal is redistributed among remaining (redundant or non-faulty) set of actuators. The proposed scheme is a unified, control allocation-based fault tolerant control which does not need to reconfigure the control system in the case of actuator fault or failure. The effectiveness of the proposed schemes is discussed with a numerical example.

Awan, Z, Kahlke, T, Ralph, P & Kennedy, P 1970, 'Chemical Named Entity Recognition with Deep Contextualized Neural Embeddings', Proceedings of the 11th International Joint Conference on Knowledge Discovery, Knowledge Engineering and Knowledge Management, 11th International Conference on Knowledge Discovery and Information Retrieval, SCITEPRESS - Science and Technology Publications, Austria, pp. 135-144.
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Copyright © 2019 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserved Chemical named entity recognition (ChemNER) is a preliminary step in chemical information extraction pipelines. ChemNER has been approached using rule-based, dictionary-based, and feature-engineered based machine learning, and more recently also deep learning based methods. Traditional word-embeddings, like word2vec and Glove, are inherently problematic because they ignore the context in which an entity appears. Contextualized embeddings called embedded language models (ELMo) have been recently introduced to represent contextual information of a word in its embedding space. In this work, we quantify the impact of contextualized embeddings for ChemNER by using Bi-LSTM-CRF (bidirectional long short term memory networks - conditional random fields) networks. We benchmarked our approach using four well-known corpora for chemical named entity recognition. Our results show that incorporation of ELMo results in statistically significant improvements in F1 score in all of the tested datasets.

Barnes-Harris, M, Johnson, M, Swan, F, Allgar, V, Booth, S, Currow, D, Hart, S & Phillips, J 1970, '8 Battery-operated fan and chronic breathlessness: does it help?', Future directions of hospice care: IPU or ITU?, Marie Curie Palliative Care Research Conference, British Medical Journal Publishing Group.
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Bedford, D, Pham, H, Sivabalan, P & Sivapalan, T 1970, 'Tight budgetary controls in early stage organisations facing high uncertainty and under-resourced environments: causes and effects', 10th Conference on Performance Measurement and Management Control, Nice, France.

Bozier, JE, Xenaki, D & Oliver, B 1970, 'E-cigarette Aerosol Stimulates Changes in Structural Proteins of the Lung', B107. EFFECTS OF E-CIGARETTES AND THEIR COMPONENTS ON RESPIRATORY DYSFUNCTION, INFLAMMATION, AND REPAIR, American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX, American Thoracic Society.
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Brunker, A, Catchpoole, D, Kennedy, P, Simoff, S & Nguyen, QV 1970, 'Two-Dimensional Immersive Cohort Analysis Supporting Personalised Medical Treatment', 2019 23rd International Conference in Information Visualization – Part II, 2019 23rd International Conference in Information Visualization – Part II, IEEE, Adelaide, Australia, pp. 34-41.
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© 2019 IEEE. Genomic data are large and complex which are challenges to visualize them effectively on ordinary screens due to the limited display spaces. Large and high resolution displays could enable the capability to show more information at once for better comprehension from the visualization. This paper presents a two-dimensional interactive visualization system and supporting algorithm for multi-dimensional large genomic data analysis that can be used in both ordinary displays or immersive environments. We provide both view of the entire patient cohort in the similarity space and the genomic details currently for comparison among the patients. Through the similarity space and on the selected genes of interest, we are able to perceive the genetic similarity throughout the cohort. From the linked heat map visualisation of the selected genes, we apply hierarchical clustering on both the horizontal and vertical axes to group together the genetically similar patients. We demonstrate the effectiveness of the visualization with two case studies on pediatric cancer patients suffering from Acute Lymphoblastic Leukemia (ALL) and from Rhabdomyosarcoma (RMS)

Büttner, TFS, Hudson, DD, Kabakova, IV & Eggleton, BJ 1970, 'Phase-locked, multiwavelength, distributed feedback brillouin laser', Proceedings 2015 European Conference on Lasers and Electro-Optics - European Quantum Electronics Conference, CLEO/Europe-EQEC 2015, European Conference on Lasers and Electro-Optics, OSA, Munich Germany.
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Phase-locked, multiwavelength laser sources with gigahertz line spacing are important for a variety of applications including arbitrary optical waveform generation and advanced telecommunications. Recently, it was demonstrated that the interplay of cascaded stimulated Brillouin scattering (SBS) and Kerr-nonlinear four-wave mixing (FWM) in Fabry-Perot resonators can generate phase-locked, equally spaced frequency components, i.e. frequency combs [1, 2]. Instead of Fabry-Perot resonances, Bragg grating resonances offer a flexible and tunable in-fiber approach that can also lower the threshold power SBS. This has recently been used to demonstrate a distributed feedback (DFB) Brillouin laser [3] based on a uniform Bragg grating with a π- phase shift manifesting in a single resonance.

Chai, R, Tran, Y, Ling, SH, Craig, A & Nguyen, HT 1970, 'Combining ICA Clustering and Power Spectral Density for Feature Extraction of Mental Fatigue of Spinal Cord Injury Patients', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 530-533.
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This paper presents the combination of clustering-based independent component analysis (ICASSO) and power spectral density (PSD) as a features extractor of mental fatigue from spinal cord injury (SCI) patients. Initially, the results show that SCI and abled-bodied groups have no differences in EEG for alert and mental fatigue states. Further, the coefficient determination (R2) is calculated for testing the variation of data alert vs. fatigue on the SCI group, resulting in a lower R2 for proposed combination of ICASSO and PSD method compared to the PSD method only. With the lower R2 values, this shows that the proposed method ICASSO and PSD is able to provide superior distinction for separating fatigue vs. alert data variation. The statistical significance is found across four EEG bands and EEG channels.

Craig, BM, De Abreu Lourenco, R & Huynh, E 1970, 'Good practices in health preference research', 11th Meeting of the International Academy of Health Preference Research, Auckland, New Zealand.

De Abreu Lourenco, R 1970, 'Grappling with the health, economics and health economics of immunotherapies', Immunotherapy Symptoms Clinical Trials: a new paradigm, Melbourne.

De Abreu Lourenco, R 1970, 'Health Economics, Drug Funding and Consumers', ANZGOG ASM, Sydney.

De Abreu Lourenco, R 1970, 'More than a fraction of value. Incorporating health economics into radiotherapy research', TROG ASM, Melbourne.

De Abreu Lourenco, R, Hegi-Johnson, F, Ball, D, Wright, G & Haas, M 1970, 'Factors influencing participation in curative intent treatment for lung cancer: A discrete choice experiment', TROG ASM, Melbourne.

DiGiacomo, M, Luckett, T, Hickman, L, Hrlec, M & Phillips, J 1970, 'Equipping tomorrow’s professional leaders in palliative care to recognise and work with assets beyond the healthcare system', Public Health and Palliative Care International, Leura.

DiGiacomo, M, Luckett, T, Hickman, L, Hrlec, M & Phillips, J 1970, 'Recognising and working with assets beyond the healthcare system: preparing future leaders in palliative care', Oceanic Palliative Care Conference, Perth.

Ding, L, Fardjahromi, MA, Bazaz, SR, Asadnia, M, Vesey, G & Warkiani, ME 1970, 'A 3D printed modular microfluidic device for large scale cell harvesting from bioreactors', 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019, pp. 604-605.
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Mesenchymal stem cell (MSC) therapy is a research hotspot nowadays due to its multiple therapeutic effects and novel application in diseases treatments. However, the current industrial technologies for their culture and harvesting are labour-intensive, time-consuming and very expensive. Herein, we presented a 3D printed modular microfluidic system consisting of micromixers and spiral channel units for cell harvesting which will greatly reduce the time and cost needed for cell harvesting, washing and cultivation. At the meantime, this system is automatic, making it compatible to the current Good Manufacturing Practice (cGMP).

Faiz, A, Rathnayake, SNH, Vermeulen, C, Timens, W, Kooistra, W, Oliver, B, Willemse, B, Ten Hacken, NHT, Heijink, IH, Brandsma, C-A & Van Den Berge, M 1970, 'Longitudinal effects of smoking cessation on DNA methylation in bronchial biopsies of COPD and asymptomatic smokers', Molecular pathology and funct. genomics, ERS International Congress 2019 abstracts, European Respiratory Society, Madrid, SPAIN.
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Garcia, JA, Sundara, N, Tabor, G, Gay, VC & Leong, TW 1970, 'Solitaire Fitness: Design of an asynchronous exergame for the elderly to enhance cognitive and physical ability', 2019 IEEE 7th International Conference on Serious Games and Applications for Health (SeGAH), 2019 IEEE 7th International Conference on Serious Games and Applications for Health (SeGAH), IEEE, IEEE, pp. 1-6.
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© 2019 IEEE. The use of exergames has shown positive results in encouraging the elderly to increase their motivation towards physical activity and rehabilitation. These games usually offer playful routines that require players to perform full body movements in order to interact with the game. While this is often well-received by elderly users, this approach has some limitations that can lead to negative effects in the aged cohort. The main one being, that gameplay and exercise must happen concurrently. This, unfortunately, places limitations on the elderly users and limits the range of exercises that can be delivered. Also, prior studies have revealed that while the aged cohort often finds this approach enjoyable, they are more inclined to exercise in more traditional ways. This paper describes the design and development of an asynchronous game, called Solitaire Fitness, where physical exercise and cognitive gameplay do not occur at the same time. The game is designed to enhance both cognitive and physical abilities. It seamlessly links a well-established card game, solitaire, and let the elderly chose the form of exercise they are familiar with and let them exercise at their own pace, allow them to fully immerse in gameplay, and ultimately increase their motivation towards an healthy active lifestyle.

Guo, K, Yu, H, Chai, R, Nguyen, H & Su, SW 1970, 'A Hybrid Physiological Approach of Emotional Reaction Detection Using Combined FCM and SVM Classifier', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 7088-7091.
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© 2019 IEEE. Users' emotional reaction capturing is one of the primary issues for brain computer interface applications. Despite the intuitive feedback provided by the qualitative methods, emotional reactions are expected to be detected and classified quantitatively. Based on the human emotion representation on physiological signal, this paper offers an hybrid approach combining electroencephalogram (EEG) and facial expression together to classify the human emotion. Several advanced signal processing techniques are used to simplify the data and extract the features involving local binary patterns (LBP), Compressed Sensing (CS) and Wavelet Transform (WT). A novel machine learning algorithm, combined Fuzzy Cognitive Maps (FCM) and Support Vector Machine (SVM) are implemented to recognise the feature patterns. The result illustrates a stable emotion classification system with 75.64% accuracy. This design can provide fast and precise emotional feedback, which would further improve the communication between human and computer.

Ha, TV & Hoang, DB 1970, 'Toward an Active Aging Society: An IT Model to Engage the Aging Population', 2019 International Conference on Information Networking (ICOIN), 2019 International Conference on Information Networking (ICOIN), IEEE, Kuala Lumpur, Malaysia.
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Many countries around the world are expecting a growing number of elderly people as the society is aging over time. This shift is expected to create a large impact on our health and social security system. The cost of having an increasing proportion of elderly people is emerging as a challenge for governments, so much that our government is encouraging people to stay in the workforce longer. As a result, the aging population requires a solution that allows them to remain productive and keeping them mentally healthy. Existing solutions rely on the benefits of social networks or service networks to keep them active and improve mental health. However, these solutions fail to allow elderly people to act as a value contributor for the society. This paper proposes the design of a new model that allows elderly people to actively and collaboratively provide value to the society through an assistive platform that integrates a service network with a social network. This model combines the advantages of the social network to connect them and utilize the advantages of the service network to create opportunities for elderly people to offer their skills and knowledge to exchange benefits with other users. The proposed model can be used as a mean to engage seniors to the community, allowing them to generate value for themselves and the community while staying mentally healthy.

Hegi-Johnson, F, Haas, M, Ball, D, Wright, G & De Abreu Lourenco, R 1970, 'P2.16-33 What Influences Patient Decision-Making About Lung-Cancer Treatment? A Discrete Choice Experiment', Journal of Thoracic Oncology, IASLC 2019 World Conference on Lung Cancer Conquering Thoracic Cancers Worldwide, Elsevier BV, Barcelona, Spain, pp. S878-S878.
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Despite major advances in radiotherapy, surgery remains the treatment of choice for patients with stage I non-small cell lung cancer. We sought to investigate what influenced preferences for surgery or SABR among cancer patients.

Hesamian, MH, Jia, W, He, X & Kennedy, PJ 1970, 'Atrous Convolution for Binary Semantic Segmentation of Lung Nodule', ICASSP 2019 - 2019 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP), ICASSP 2019 - 2019 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP), IEEE, Brighton. UK, pp. 1015-1019.
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© 2019 IEEE. Accurately estimating the size of tumours and reproducing their boundaries from lung CT images provides crucial information for early diagnosis, staging and evaluating patients response to cancer therapy. This paper presents an advanced solution to segment lung nodules from CT images by employing a deep residual network structure with Atrous convolution. The Atrous convolution increases the field of view of the filters and helps to improve classification accuracy. Moreover, in order to address the significant class imbalance issue between the nodule pixels and background non-nodule pixels, a weighted loss function is proposed. We evaluate our proposed solution on the widely adopted benchmark dataset LIDC. A promising result of an average DCS of 81.24% is achieved, outperforming the state of the arts. This demonstrates the effectiveness and importance of applying the Atrous convolution and weighted loss for such problems.

Hofman, M, Murphy, DG, Williams, S, Nzenza, T, Herschtal, A, Matera, A, Marusic, P, De Abreu Lourenco, R, Bailey, DL, Iravani, A, Hicks, RJ, Francis, RJ & Lawrentschuk, N 1970, 'The “ProPSMA Study” clinical trial protocol: A prospective randomized multi-center study of the impact of Ga-68 PSMA PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy.', Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), pp. TPS138-TPS138.
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TPS138 Background: Disease persistence or relapse following curative-intent surgery or radiotherapy of high-risk prostate cancer is not uncommon. This is attributable, in part, to a failure of accurate staging with diagnostic imaging being insensitive for detection of small volume metastatic disease. Prostate-specific-membrane-antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is a new whole body scanning technique that enables visualisation of prostate cancer with high sensitivity. The hypotheses of this study are that PSMA-PET/CT (a) has improved diagnostic accuracy compared to conventional imaging, (b) should be used as a first-line diagnostic test for staging, (c) the improved diagnostic accuracy will result in significant management impact and (d) provides economic benefits when incorporated into the management algorithm. Methods: This is a 300 patient phase III multi-centre randomized study of patients with untreated high-risk prostate cancer defined by Gleason grade group 3-5, PSA ≥ 20ng/ml or clinical stage ≥ T3. Patients are randomized to Gallium-68-PSMA11 PET/CT or conventional imaging, consisting of computer tomography of the abdomen/pelvis and bone scintigraphy with SPECT/CT. Patients with negative, equivocal or oligometastatic disease cross-over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT to conventional imaging for detecting nodal or distant metastatic disease. Accuracy is defined by a pre-defined “ground truth” scoring system incorporating histopathologic, imaging and clinical follow-up at six months post randomisation. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross-over, health economics, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer term follow-up will also assess the prognostic value of a nega...

Huang, Y, Song, R, Chen, W, Yu, H, Argha, A, Celler, BG & Su, S 1970, 'The effects of different tracking tasks on muscle synergy through visual feedback', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 417-420.
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© 2019 IEEE. By recruiting a modular organization of muscle with relative activities, the arm motion can be indicated by the neural system and generated for performing a variety of motor tasks. In this study, a Non-negative Matrix Factorization with initial estimation is applied to identify and extract primary muscle synergies and their activation patterns from the processed EMG recordings during three multidirectional tracking tasks with visual feedback interaction. The effects of task variety and tracking accuracy by visual feedback on muscle synergies and their activation patterns are explored by statistic analysis. The results showed that only the task variety affected what synergies were indicated by the neural system, but both task variety and visual feedback affected the duration and magnitude of the primary synergies. Thus, for active rehabilitation application, it is advised that if the purpose is to enhance the synergy indication from the neural system, the task completion accuracy should be emphasized, but if the purpose is to expand the motion area, the task variety should be diversified.

Khan, TA, Ling, SH & Mohan, AS 1970, 'Advanced Gravitational Search Algorithm with Modified Exploitation Strategy', 2019 IEEE International Conference on Systems, Man and Cybernetics (SMC), 2019 IEEE International Conference on Systems, Man and Cybernetics (SMC), IEEE, Bari, Italy, pp. 1066-1070.
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Gravitational search algorithm (GSA) is a novel technique as compared to other heuristic methods and depends pon the gravitational forces between masses. It showed better performance in terms of convergence but has slow exploitation ability due to the fitness function effect on masses; they are getting heavier after every iteration. Therefore, masses are getting closer to each other and nullify the gravitational forces on each other avoiding them from swiftly exploiting the optimum. In order to solve this problem in this paper, an advanced gravitational search algorithm (AGSA) with modified exploitation strategy is proposed. The reason for the modification is that the agents will reach the optimum point swiftly and the convergence is much faster as compared to the standard and other improved versions of GSA available in the literature. AGSA is also compared with the standard and modified Particle Swarm optimization algorithm in this paper. Five benchmark functions have been implemented to assess the efficiency of the presented algorithm. In addition, a standard, constrained, design problem of a pressure vessel design is also used to examine the efficiency of the proposed technique. Simulation results empirically validated that the presented algorithm has remarkably better results in accordance with convergence and solution stability when compared to the other methods.

Khan, TA, Zain-Ul-Abideen, K & Ling, SH 1970, 'A Hybrid Advanced PSO-Neural Network System', 2019 IEEE International Conference on Systems, Man and Cybernetics (SMC), 2019 IEEE International Conference on Systems, Man and Cybernetics (SMC), IEEE, Bari, ITALY, pp. 1626-1630.
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In this paper, a combination of Advanced Particle Swarm Optimization (APSO) and Neural Network are presented to compensate the drawbacks of both the techniques and utilize the strong attributes to form a hybrid system called Hybrid Advance Particle Swarm Optimization-Neural Network System (HAPSONNS). APSO is used for the training of the neural network. In the initial phases of the search, PSO has swift convergence for global optimum, but later it suffers from slow convergence around the global optimum position. On the contrary, the gradient method attains prior to convergence around the global optimum point, therefore, attaining better accuracy in terms of convergence. This paper elucidates the usage of APSO applied to feedforward neural network to improve the classification accuracy of the network and also decreases the network training time.

Khan, TA, Zain-Ul-Abideen, K & Ling, SH 1970, 'A Modified Particle Swarm Optimization Algorithm Used for Feature Selection of UCI Biomedical Data Sets', 2019 60th International Scientific Conference on Information Technology and Management Science of Riga Technical University (ITMS), 2019 60th International Scientific Conference on Information Technology and Management Science of Riga Technical University (ITMS), IEEE, Riga, LATVIA.
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Khuat, TT & Gabrys, B 1970, 'Accelerated Training Algorithms of General Fuzzy Min-Max Neural Network Using GPU for Very High Dimensional Data', Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), International Conference on Neural Information Processing, Springer International Publishing, Sydney, Australia, pp. 583-595.
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© Springer Nature Switzerland AG 2019. One of the issues of training a general fuzzy min-max neural network (GFMM) on very high dimensional data is a long training time even if the number of samples is relatively low. This is a quite common problem shared by many prototype-based methods requiring frequently repeated distance or similarity calculations. This paper proposes the method of accelerating the learning algorithms of the GFMM by, first, reformulating and representing them in a format allowing for their parallel execution and subsequently leveraging the computational power of the graphics processing unit (GPU). The original implementation of GFMM is modified by matrix computations to be executed on the GPU for the very high-dimensional datasets. The empirical results on two very high-dimensional datasets indicated that the training and testing processes performed on Nvidia Quadro P5000 GPU were from 10 to 35 times faster compared to those running serially on the Xeon CPU while retaining the same classification accuracy.

Kocbek, S & Gabrys, B 1970, 'Automated Machine Learning Techniques in Prognostics of Railway Track Defects', 2019 International Conference on Data Mining Workshops (ICDMW), 2019 International Conference on Data Mining Workshops (ICDMW), IEEE, China, pp. 777-784.
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© 2019 IEEE. The readiness and usefulness of Automated Machine Learning (AutoML) methods in classification of railway track defects is explored. Safety of railway networks is the top priority in the railroad industry, and track defects are a common cause of train accidents and service disruptions around the world. Effective classification and prediction of these defects based on historical inspection data can help in planning maintenance activities before critical defects occur. This increases safety of the network and lowers costs of the maintenance. The experimental analysis carried out on data from an international predictive modelling competition has shown that the proposed AutoML approaches resulted in an improved performance in comparison to the competition winning solutions and have an excellent potential for building robust predictive models in railway industry.

Kocbek, S, Kocbek, P, Zupanic, T, Stiglic, G & Gabrys, B 1970, 'Using (Automated) Machine Learning and Drug Prescription Records to Predict Mortality and Polypharmacy in Older Type 2 Diabetes Mellitus Patients', Communications in Computer and Information Science, International Conference on Neural Information Processing, Springer International Publishing, Sydney, NSW, Australia, pp. 624-632.
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We analyse a large drug prescription dataset and test the hypothesis that drug prescription data can be used to predict further complications in older patients newly diagnosed with type 2 diabetes mellitus. More specifically, we focus on mortality and polypharmacy prediction. We also examine the balance between interpretability and predictive performance for both prediction tasks, and compare performance of interpretable models with models generated with automated methods. Our results show good predictive performance in the polypharmacy prediction task with AUC of 0.859 (95% CI: 0.857–0.861). On the other hand, we were only able to achieve the average predictive performance for mortality prediction task with AUC of 0.754 (0.747–0.761). It was also shown that adding additional drug related features increased the performance only in the polypharmacy prediction task, while additional information on prescribed drugs did not influence the performance in the mortality prediction. Despite the limited success in mortality prediction, this study demonstrates the added value of the systematic collection and use of Electronic Health Record (EHR) data in solving the problem of polypharmacy related complications in older age.

Kulasinghe, A, Kapeleris, J, Kenny, L, Warkiani, M, Vela, I, Thiery, J-P, O'Byrne, K & Punyadeera, C 1970, 'Abstract 1333: Isolation, characterization and expansion of circulating tumor cells in solid cancers', Cancer Research, American Association for Cancer Research (AACR), pp. 1333-1333.
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Abstract Metastasis in cancer patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in a number of solid tumor types. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. Head and Neck cancer (n=300) and lung cancer (n=80) patients were recruited to investigate the prognostic role of CTCs. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, inertial microfluidics) using matched patient samples which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR-amplification, ALK-translocations). In HNC, the presence of CTC clusters associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression free survival (PFS) (Hazard ratio [HR]: 4.946; 95% confidence internal [CI]:1.571-15.57; P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P=0.0485). In a proof of principle study, we were able to demonstrate for the first time, short-term patient derived CTC cultures outside the patient’s body from 7/18 HNC samples (4/7 HPV-positive). Recently, we have preliminary data that suggests that PD-L1 is frequently expressed on CTCs in HNC and lung cancer and an immunoscore may be able to identify patients likely to benefit ...

LA, QT, REN, B, LOGAN, GJ, CUNNINGHAM, SC, KHANDEKAR, N, NASSIF, NT, O'BRIEN, BA, ALEXANDER, IE & SIMPSON, AM 1970, '1778-P: Delivery of the Insulin Gene Using an Integrating Adeno-Associated Viral Vector (AAV) to Diabetic NOD Mice', Diabetes, 79th Scientific Sessions of the American-Diabetes-Association (ADA), American Diabetes Association, San Francisco, CA, pp. 1778-P.
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Previously we introduced furin-cleavable human insulin (INSFUR) to the livers in several animal models using a lentiviral vector. Reversal of diabetes with normal glucose tolerance and pancreatic transdifferentiation was seen. The aim of the present study was to ascertain if we could similarly reverse diabetes in the non-obese diabetic (NOD) mouse using a clinically-applicable AAV system to deliver INSFUR ± the β-cell transcription factor (TF) Pdx1 to the livers of the diabetic mice. The traditional AAV8 that allows predominantly episomal expression, and the hybrid AAV8/piggyBac that results in transgene integration into the host genome were used. Weight and blood glucose levels were monitored. Intraperitoneal glucose tolerance tests (IPGTTs) were performed. Immunofluorescence was carried out to monitor transduction utilising marker genes Venus and mCherry. RT-PCR was used to identify expression of pancreatic genes. Diabetic mice that received intraperitoneal (IP) injections of AAV8-INSFUR-mCherry (2.3x 1010-4.5x1010vg) became hypoglycaemic with abnormal responses to IPGTTs. No β-cell TF could be detected in the livers. Reversal of diabetes could not be achieved in the mice (n=8) that received combinations of AAV8-INSFUR-venus (5x1010 or 7.5x1010vg) and AAV8-Pdx1-mCherry (7.5x1010 vg). Both INSFUR and Pdx1 were detected using RT-PCR and immunofluorescence showed the expression of both marker genes. IPGTTs were abnormal; however, the β-cell TF MafA was detected by RT-PCR. Euglycaemia and normal IPGTTs were achieved in mice (n=4) that received AAV8/piggyBac-INSFUR-mCherry (transposase 4x1010 vg and transposon 3.5x1010 vg). The INSFUR gene and the β-cell TFs NKx6.1 and MafA were detected in the livers, however wider evidence of pancreatic transdifferentiation was not seen. This is the first in vivo study using the hybrid AAV8/piggyBac system to treat type 1 diabetes (T1D). The AAV system, with further development, may hold promise for gene therapy ...

Ling, SH, Makgawinata, H, Monsivais, FH, dos Santos Goncalves Lourenco, A, Lyu, J & Chai, R 1970, 'Classification of EEG Motor Imagery Tasks Using Convolution Neural Networks', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 758-761.
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Electroencephalograph (EEG) is a highly nonlinear data and very difficult to be classified. The EEG signal is commonly used in the area of Brain-Computer Interface (BCI). The signal can be used as an operative command for directional movements for a powered wheelchair to assist people with disability in performing the daily activity.In this paper, we aim to classify Electroencephalograph EEG signals extracted from subjects which had been trained to perform four Motoric Imagery (MI) tasks for two classes. The classification will be processed via a Convolutional Neural Network (CNN) utilising all 22 electrodes based on 10-20 system placement. The EEG datasets will be transformed into scaleogram using Continuous Wavelet Transform (CWT) method.We evaluated two different types of image configuration, i.e. layered and stacked input datasets. Our procedure starts from denoising the EEG signals, employing Bump CWT from 8-32 Hz brain wave. Our CNN architecture is based on the Visual Geometry Group (VGG-16) network. Our results show that layered image dataset yields a high accuracy with an average of 68.33% for two classes classification.

Lyu, J, Ling, SH, Banerjee, S, Zheng, JJY, Lai, K-L, Yang, D, Zheng, Y-P & Su, S 1970, '3D Ultrasound Spine Image Selection Using Convolution Learning-to-Rank Algorithm', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, GERMANY, pp. 4799-4802.
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© 2019 IEEE. 3D Ultrasound imaging has become an important means of scoliosis assessment as it is a real-time, cost-effective and radiation-free imaging technique. However, the coronal images from different depths of a 3D ultrasound image have different imaging definitions. So there is a need to select the coronal image that would give the best image definition. Also, manual selection of coronal images is time-consuming and limited to the discretion and capability of the assessor. Therefore, in this paper, we have developed a convolution learning-to-rank algorithm to select the best ultrasound images automatically using raw ultrasound images. The ranking is done based on the curve angle of the spinal cord. Firstly, we approached the image selection problem as a ranking problem; ranked based on probability of an image to be a good image. Here, we use the RankNet, a pairwise learning-to-rank method, to rank the images automatically. Secondly, we replaced the backbone of the RankNet, which is the traditional artificial neural network (ANN), with convolution neural network (CNN) to improve the feature extracting ability for the successive iterations. The experimental result shows that the proposed convolutional RankNet achieves the perfect accuracy of 100% while conventional DenseNet achieved 35% only. This proves that the convolutional RankNet is more suitable to highlight the best quality of ultrasound image from multiple mediocre ones.

Mac Aogáin, M, Kumar, JN, Lim, AYH, Low, TB, Ong, TH, Chew, FT, Oliver, B, Keir, HR, Koh, MS, Abisheganaden, JA, Tsaneva-Atanasova, K, Chalmers, JD & Chotirmall, SH 1970, ''Integrative Microbiomics' Through Similarity Network Fusion Identifies Clinically Relevant Bronchiectasis Phenotypes', D97. FUNGAL INFECTIONS: FROM BENCH TO BEDSIDE, American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX, American Thoracic Society.
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Mahdavi, F, Hayati, H, Kennedy, P & Eager, D 1970, 'Ageing and resulting injuries – effects on racing greyhounds', European Society of Biomechanics, European Society of Biomechanics, Vienna, Austria.

Mahdavi, F, Hayati, H, Kennedy, P & Eager, D 1970, 'Effects of the number of starts on greyhound racing dynamics', International Society of Biomechanics Conference, International Society of Biomechanics Conference, Calgary, Canada.

McCarthy, M, Lorenco, RDA, Gillam, L, McMillan, L, Sullivan, M & Downie, P 1970, 'Personalised Medicine in Paediatric Cancer Care: What Matters in Decision-Making?', PEDIATRIC BLOOD & CANCER, 51st Congress of the International Society of Paediatric Oncology, WILEY, Lyon, France, pp. S11-S12.

Mitchell, A, Mourad, B, Morgan, L, Oliver, B & Glanville, A 1970, 'DETERMINING THE IMPACT OF RESPIRATORY VIRUSES ON AT RISK PATIENT POPULATIONS', RESPIROLOGY, WILEY, pp. 22-22.

Mulhern, B, Norman, R, De Abreu Lourenco, R, Malley, J, Street, D & Viney, R 1970, 'Investigating the relative value of health and social care related quality of life using a discrete choice experiment', Social Science & Medicine, 38th Annual Australian Health Economics Society Conference, Elsevier BV, Perth, pp. 28-37.
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Naji, M, Al-Ani, A, Braytee, A, Anaissi, A & Kennedy, P 1970, 'Queue Formation Augmented with Particle Swarm Optimisation to Improve Waiting Time in Airport Security Screening', Advances in Intelligent Systems and Computing, Workshops of the 33rd International Conference on Advanced Information Networking and Applications, Springer International Publishing, Japan, pp. 923-935.
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© 2019, Springer Nature Switzerland AG. Airport security screening processes are essential to ensure the safety of both passengers and the aviation industry. Security at airports has improved noticeably in recent years through the utilisation of state-of-the-art technologies and highly trained security officers. However, maintaining a high level of security can be costly to operate and implement. It may also lead to delays for passengers and airlines. This paper proposes a novel queue formation method based on a queueing theory model augmented with a particle swarm optimisation method known as QQT-PSO to improve the average waiting time in airport security areas. Extensive experiments were conducted using real-world datasets collected from Sydney airport. Compared to the existing system, our method significantly reduces the average waiting time and operating cost by 11.89% compared to the one-queue formation.

Ngo, CQ, Chai, R, Nguyen, TV, Jones, TW & Nguyen, HT 1970, 'Nocturnal Hypoglycemia Detection using EEG Spectral Moments under Natural Occurrence Conditions', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 7177-7180.
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This paper is concerned with a study of hypoglycemia under natural occurrence conditions at night time. Five adolescents with type 1 diabetes (T1D) participated in the experiments. Patients' blood glucose profiles were interpolated to estimate the intermediate values. The proposed system used spectral moments of electroencephalogram (EEG) signals from central and occipital areas as features for detecting hypoglycemia. We found that hypoglycemia could be detected non-invasively using EEG spectral moments. During hypoglycemic episodes, theta moments increased significantly (P<; 0.005) whereas beta moments decreased significantly (P<; 0.001). Based on the optimal network architecture associated with the highest log evidence, the proposed optimal Bayesian neural network resulted in a sensitivity of 82% and a specificity of 52%. In addition, the estimated blood glucose profiles showed a significant correlation (P<; 1e-6) with interpolated blood glucose values in the test set.

Ngo, CQ, Chai, R, Nguyen, TV, Jones, TW & Nguyen, HT 1970, 'Nocturnal Hypoglycemia Detection using Optimal Bayesian Algorithm in an EEG Spectral Moments Based System', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 5439-5442.
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This paper presents a hypoglycemia detection system using electroencephalogram (EEG) spectral moments from 8 patients with type 1 diabetes (T1D) at night time. Four channels (C3, C4, O1, and O2) associated with glycemic episodes were analyzed. Spectral moments were applied to EEG signal and its corresponding speed and acceleration. During hypoglycemia, theta moments increased significantly (P<; 0.001) and alpha moments decreased significantly (P<; 0.001). The system used an optimal Bayesian neural network for detecting hypoglycemic episodes. Based on the optimal network architecture with the highest log evidence, the final classification results for the test set were 79% and 51% in sensitivity and specificity, respectively. Essentially, the estimated blood glucose profiles correlated significantly to actual values in the test set (P<; 0.0001). Using error grid analysis, 93% of the estimated values were clinically acceptable.

Nguyen, L & Miro, JV 1970, 'Acoustic Sensor Networks and Mobile Robotics for Sound Source Localization', 2019 IEEE 15th International Conference on Control and Automation (ICCA), 2019 IEEE 15th International Conference on Control and Automation (ICCA), IEEE, Edinburgh, UK, pp. 1453-1458.
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© 2019 IEEE. Localizing a sound source is a fundamental but still challenging issue in many applications, where sound information is gathered by static and local microphone sensors. Therefore, this work proposes a new system by exploiting advances in sensor networks and robotics to more accurately address the problem of sound source localization. By the use of the network infrastructure, acoustic sensors are more efficient to spatially monitor acoustical phenomena. Furthermore, a mobile robot is proposed to carry an extra microphone array in order to collect more acoustic signals when it travels around the environment. Driving the robot is guided by the need to increase the quality of the data gathered by the static acoustic sensors, which leads to better probabilistic fusion of all the information gained, so that an increasingly accurate map of the sound source can be built. The proposed system has been validated in a real-life environment, where the obtained results are highly promising.

Nguyen, L, Miro, JV & Qiu, X 1970, 'Can a Robot Hear the Shape and Dimensions of a Room?', IEEE International Conference on Intelligent Robots and Systems, IEEE/RSJ International Conference on Intelligent Robots and Systems, IEEE, Macau, China, pp. 5346-5351.
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Knowing the geometry of a space is desirable for many applications, e.g.sound source localization, sound field reproduction or auralization. Incircumstances where only acoustic signals can be obtained, estimating thegeometry of a room is a challenging proposition. Existing methods have beenproposed to reconstruct a room from the room impulse responses (RIRs). However,the sound source and microphones must be deployed in a feasible region of theroom for it to work, which is impractical when the room is unknown. This workpropose to employ a robot equipped with a sound source and four acousticsensors, to follow a proposed path planning strategy to moves around the roomto collect first image sources for room geometry estimation. The strategy caneffectively drives the robot from a random initial location through the room sothat the room geometry is guaranteed to be revealed. Effectiveness of theproposed approach is extensively validated in a synthetic environment, wherethe results obtained are highly promising.

Nguyen, L, Miro, JV, Shi, L & Vidal-Calleja, T 1970, 'Gaussian Mixture Marginal Distributions for Modelling Remaining Pipe Wall Thickness of Critical Water Mains in Non-Destructive Evaluation', 2019 IEEE International Conference on Cybernetics and Intelligent Systems (CIS) and IEEE Conference on Robotics, Automation and Mechatronics (RAM), IEEE International Conference on Cybernetics and Intelligent Systems, and Robotics, Automation and Mechatronics, IEEE, Bangkok, Thailand.
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Rapidly estimating the remaining wall thickness (RWT) is paramount for thenon-destructive condition assessment evaluation of large critical metallicpipelines. A robotic vehicle with embedded magnetism-based sensors has beendeveloped to traverse the inside of a pipeline and conduct inspections at thelocation of a break. However its sensing speed is constrained by the magneticprinciple of operation, thus slowing down the overall operation in seekingdense RWT mapping. To ameliorate this drawback, this work proposes the partialscanning of the pipe and then employing Gaussian Processes (GPs) to infer RWTat the unseen pipe sections. Since GP prediction assumes to have normallydistributed input data - which does correspond with real RWT measurements -Gaussian mixture (GM) models are proven in this work as fitting marginaldistributions to effectively capture the probability of any RWT value in theinspected data. The effectiveness of the proposed approach is extensivelyvalidated from real-world data collected in collaboration with a water utilityfrom a cast iron water main pipeline in Sydney, Australia.

Nguyen, TV, Tran, TS, Center, JR & Eisman, JA 1970, 'Small individual-level increase in bone mineral density translated into substantial population-level decrease in fracture incidence: revisiting Goeffrey Rose's axiom', JOURNAL OF BONE AND MINERAL RESEARCH, Annual Meeting of the American-Society-for-Bone-and Mineral Research, WILEY, Orlando, FL, pp. 250-250.

Pham, M, Hoang, DB & Chaczko, Z 1970, 'Realization of congestion-aware energy-aware virtual link embedding', 2019 29th International Telecommunication Networks and Applications Conference (ITNAC), 2019 29th International Telecommunication Networks and Applications Conference (ITNAC), IEEE, Auckland, New Zealand.
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Network virtualization is an inherent component of future internets. Network resources are virtualized and provisioned to users on demand. The virtual network embedding entails two processes: node mapping and link mapping. However, efficient and practical solutions to the link mapping problem in software-defined networks (SDN) and data centers are still lacking. This paper proposes a solution to the link mapping (LiM) process that can dynamically interact with the routing protocols of the substrate network to allocate virtual link requests to the underlying substrate links, satisfies optimizing cost, minimizing energy consumption, and avoiding congestion (CEVNE) concurrently. CEVNE LiM is realized as a composite application on top of the SDN controller running the Segment Routing (SR) application. The performance of the CEVNE LiM algorithm is compared with the k-shortest path link mapping algorithm and shows its superior performance in terms of the overall runtime, the average path length, the average node stress, the average link stress, and the overall energy consumption.

Phillips, J 1970, 'Older cancer patients: The evolution of geriatric oncology and palliative care', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, WILEY, pp. 95-96.

Rao, A, DiGiacomo, M, Newton, PJ, Phillips, JL & Hickman, LD 1970, 'Meditation and Secondary Prevention of Depression and Anxiety in Heart Disease: a Systematic Review', Mindfulness, Australian Cardiac Rehabilitation Association Conference, Adelaide.
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Heart disease is the leading cause of global mortality, accounting for 13.7 million deaths annually. Optimising depression and anxiety symptoms in adults with heart disease is an international priority. Heart disease secondary prevention is best achieved through implementation of sustainable pharmacological and non-pharmacological interventions, including meditation. Meditation is a means of generating self-awareness and has implications for enhanced self-management of depression and anxiety symptoms. This review aims to identify high-level quantitative evidence for meditation interventions designed to improve depression and/or anxiety symptoms among adults with heart disease and ascertain the most important elements of meditation interventions that facilitate positive depression and/or anxiety outcomes. This systematic review and narrative synthesis was completed in accordance with the PRISMA Statement and has adhered to the Cochrane Risk of Bias guideline. Six databases were searched between 1975 and 2017. Statistically significant outcomes were demonstrated in over half (5/9) of phase II meditation studies for depression and/or anxiety and involved 477 participants. Meditation interventions that generated positive outcomes for depression and/or anxiety included elements such as focused attention to body parts (or body scan) (3/4 studies) and/or group meetings (4/5 studies). Meditation is a means of reframing heart disease outpatient services towards an integrated model of care. Future adequately powered phase III studies are needed to confirm which meditation elements are associated with reductions in depression and anxiety; and the differential effects between concentrative and mindfulness-based meditation types among adults with heart disease.

Rao, A, DiGiacomo, M, Phillips, J & Hickman, L 1970, 'Health professional perspectives of the organisational barriers and facilitators to implementing meditation in heart disease clinical settings', Australian Cardiac Rehabilitation Association, Kirribilli, NSW.

Rao, A, Zecchin, R, Newton, P, Phillips, J, DiGiacomo, M, Denniss, A & Hickman, L 1970, 'The Prevalence of Anxiety and Depression in a Cardiac Rehabilitation Population and its Impact on Adherence: A Cohort Study', Heart, Lung and Circulation, Australian Cardiac Rehabilitation Association, Elsevier BV, Kirribilli, NSW, pp. S375-S375.
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Reddy, K, Zakarya, R & Oliver, BG 1970, 'Epigenetic-like regulation of signalling proteins in chronic obstructive pulmonary disease', Airway cell biology and immunopathology, ERS International Congress 2019 abstracts, European Respiratory Society, Madrid, SPAIN.
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Rezaeian, M, Butlin, M, Golzan, SM, Graham, SL & Avolio, AP 1970, 'A novel method for retinal vessel segmentation and diameter measurement using high speed video', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 2781-2784.
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Studying dynamic characteristics of retinal vessels, as opposed to static measures, may provide additional insight into pathophysiological changes associated with local and systemic abnormalities such as glaucoma and hypertension. Various approaches have been developed to derive static biomarkers from retinal still images, but not many for dynamic analysis of video sequences. This study presents a novel method for the assessment of time-dependent diameter changes in high-speed videos (125 fps) from the rat retina. The proposed method is composed of a vessel segmentation and a diameter measurement module. The specificity and sensitivity of the segmentation method over 25 images were 95.1% and 97.3% respectively. The mean and standard deviation of the diameter measurement errors were -0.147±0.41 pixels over 100 measurements.

Shariflou, S, Agar, A, Rose, KA & Golzan, M 1970, 'The accuracy of spontaneous venous pulsation assessment in discriminating glaucoma from glaucoma suspects', INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), ASSOC RESEARCH VISION OPHTHALMOLOGY INC, CANADA, Vancouver.

Si, L, Eisman, JA, Winzenberg, T, Sanders, KM, Center, JR, Nguyen, TV, Chen, M & Palmer, AJ 1970, 'RESIDUAL LIFETIME FRACTURE RISKS AND YEARS OF LIFE LOSS DUE TO OSTEOPOROSIS IN THE AUSTRALIAN POPULATION: AN APPLICATION OF AN OS'T'EOPOROSIS HEALTH ECONOMIC MODEL', OSTEOPOROSIS INTERNATIONAL, World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO), SPRINGER LONDON LTD, Paris, FRANCE, pp. S306-S307.

Thng, KX, Mac Aogáin, M, Ali, NABM, Hui, AGY, Hou, ALY, Low, TB, Ong, TH, Oliver, B, Koh, MS, Abisheganaden, J, Chalmers, JD & Chotirmall, SH 1970, 'Viral prevalence in stable bronchiectasis: analysis of the Cohort of Asian and Matched European Bronchiectasis (CAMEB)', Respiratory infections, ERS International Congress 2019 abstracts, European Respiratory Society.
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Thompson, C, Berthon, B, Scott, H, Gibson, P, Young, P, Oliver, B & Wood, L 1970, 'MACRONUTRIENT EFFECTS ON BRONCHODILATOR RESPONSIVENESS IN OBESE ASTHMA', RESPIROLOGY, WILEY, pp. 61-61.

Tran, TS, Bliuc, D, Hansen, L, Abrahamsen, B, van den Bergh, J, Eisman, JA, van Geel, T, Geusens, P, Vestergaard, P, Nguyen, TV & Center, JR 1970, 'Multimorbidity and long-term mortality following a specific fragility fracture: Latent class analysis of a nationwide population-based cohort', JOURNAL OF BONE AND MINERAL RESEARCH, Annual Meeting of the American-Society-for-Bone-and Mineral Research, WILEY, Orlando, FL, pp. 385-386.

Tran, TS, Bliuc, D, O'Donoghue, S, Hansen, L, Abrahamsen, B, van den Bergh, J, van Geel, T, Geusens, P, Vestergaard, P, Nguyen, TV & Center, JR 1970, 'Trajectories to subsequent admissions and mortality following a specific fragility fracture: A nationwide population-based follow-up study', JOURNAL OF BONE AND MINERAL RESEARCH, Annual Meeting of the American-Society-for-Bone-and Mineral Research, WILEY, Orlando, FL, pp. 386-386.

van Reyk, D, Oliver, B, Capistrano, S, Komalla, V, Haghi, M & Zosky, G 1970, 'Pro-inflammatory effects of exposure of the combination of silicon- and iron-containing particles upon human lung fibroblasts', Airway cell biology and immunopathology, ERS International Congress 2019 abstracts, European Respiratory Society, Madrid, SPAIN.
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Vranken, L, Wyers, CE, Van der Velde, RY, De Bruin, IJA, Van den Bergh, JPW, Janzing, HMJ, Kaarsemakers, S, Eisman, JA, Center, JR, Nguyen, TV, Bliuc, D, Tran, T & Geusens, PPMM 1970, 'The imminent subsequent fracture risk in patients with a recent fracture at the FLS is mainly associated with falls - a 3 year prospective cohort study.', JOURNAL OF BONE AND MINERAL RESEARCH, Annual Meeting of the American-Society-for-Bone-and Mineral Research, WILEY, Orlando, FL, pp. 181-182.

Wadhwa, R, Paudel, KR, Nee, TX, Xin Lau, NJ, Zeeshan, F, Madheswaran, T, Panneerselvam, J, Reddy, K, Hsu, A, Oliver, B, Hansbro, P, Chellappan, DK & Dua, K 1970, 'Preparation, characterisation and biological applications of Rutin loaded liquid crystalline nanoparticles in targeting airway diseases', Sydney New Horizons-2019, Sydney New Horizons-2019.

Wang, B, Hui, C, Zhou, S, Saad, S, Chan, YL & Oliver, BGG 1970, 'L-Carnitine mitigates impact of maternal smoking on lung health in mice offspring', Allergy and immunology, ERS International Congress 2019 abstracts, European Respiratory Society.
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Warkiani, ME 1970, 'Label-free Cell Sorting Using Inertial Microfluidics', 2019 13TH IEEE INTERNATIONAL CONFERENCE ON NANO/MOLECULAR MEDICINE & ENGINEERING (IEEE-NANOMED 2019), 13th IEEE International Conference on Nano/Molecular Medicine and Engineering (IEEE NANOMED), IEEE, SOUTH KOREA, Gwangju, pp. 52-53.

Warkiani, ME, Moloudi, R, Oh, S & Naing, MW 1970, 'Inertial-based Microcarrier-cell retention in bioprocessing', Cytotherapy, Elsevier BV, Australia, pp. e4-e5.
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Watson, K, Lewis, J & Parker, D 1970, 'A career in aged care: mapping final-year nursing perspectives', Australian Association of Gerontology, Sydney.

Watterson, P, Gorrie, C & Herok, G 1970, 'Invited Faculty Abstracts from the International Neuromodulation Society’s 14th World Congress', Neuromodulation: Technology at the Neural Interface, International Neuromodulation Society 14th World Congress, Elsevier BV, Sydney, Australia, pp. e296-e584.
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White, K, De Abreu Lourenco, R, Kenny, P, Lehane, L & King, T 1970, 'Understanding the financial impact of cancer: Examining the ‘COST’ Measure in the Australian context.', Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, pp. e340-e340.
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Zakarya, R, Chen, H, Brandsma, C-AA, Adcock, IM & Oliver, BGG 1970, 'Small Airway Fibrosis in COPD Is Mediated by Histone Acetylation', C108. COPD: PHENOTYPE, MECHANISM, AND TREATMENT, American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX, American Thoracic Society, Dallas, TX.
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Zhang, M, Li, H & Su, S 1970, 'High Dimensional Bayesian Optimization via Supervised Dimension Reduction', Proceedings of the Twenty-Eighth International Joint Conference on Artificial Intelligence, Twenty-Eighth International Joint Conference on Artificial Intelligence {IJCAI-19}, International Joint Conferences on Artificial Intelligence Organization, Macao, China, pp. 4292-4298.
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Bayesian optimization (BO) has been broadly applied to computational expensive problems, but it is still challenging to extend BO to high dimensions. Existing works are usually under strict assumption of an additive or a linear embedding structure for objective functions. This paper directly introduces a supervised dimension reduction method, Sliced Inverse Regression (SIR), to high dimensional Bayesian optimization, which could effectively learn the intrinsic sub-structure of objective function during the optimization. Furthermore, a kernel trick is developed to reduce computational complexity and learn nonlinear subset of the unknowing function when applying SIR to extremely high dimensional BO. We present several computational benefits and derive theoretical regret bounds of our algorithm. Extensive experiments on synthetic examples and two real applications demonstrate the superiority of our algorithms for high dimensional Bayesian optimization.

Zhang, X, Zhang, X, Verma, S, Liu, Y, Blumenstein, M & Li, J 1970, 'Detection of Anomalous Traffic Patterns and Insight Analysis from Bus Trajectory Data', PRICAI 2019: Trends in Artificial Intelligence, The 16th Pacific Rim International Conference on Artificial Intelligence, Springer International Publishing, Cuvu, Fiji, pp. 307-321.
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Zhang, Y, Yao, D, Tie, Y, Wang, Y, Zhang, X, Cui, Y, Hao, J, Wu, X, Su, S & Xu, P 1970, 'Identification of Neuromuscular Causal Relationship Between Brain and Muscles in Limb Movement by Using Ensemble Empirical Mode Decomposition based Causal Decomposition', 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), IEEE, Berlin, Germany, pp. 2667-2670.
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This paper proposes the potential extension of Ensemble Empirical Mode Decomposition based Causal Decomposition (EEMD-CD) to the physiological system. The neural basis of Volitional Motor Control (VMC), resulting in skilled motor behaviors through a connected interaction between limb biomechanical properties and Central Neural System (CNS), has been well documented. Specifically, the Primary Motor Cortex (M1) contributes volitional and goal-directed limb movements in terms of motor planning and motor behavior. The actual applications of causality detection approaches were still dominated by the prediction concept, i.e., Granger Causality (GC). This study concerns clearly some of components of M1 regulating motor properties of upper limbs, and holds the neuroscience finding from which the bi-directional causal interaction in brain and muscles has been concluded. The study performs an experiment by which Electromyography (EMG) of limb muscles and Electroencephalography (EEG) across from prefrontal cortex to M1, were synchronously acquired during wrist extensions. It also provides a valid example of how the casuality can be approached by EEMD-CD and offers a first step in the identification of casual relationship in mutual physiological systems.

Foley, C, Hergesell, A, Almond, B & Darcy, S University of Technology Sydney 2019, ActivateUTS sport and social clubs: Empowering students to grow, contribute and make a difference, Sydney.
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This report presents thefindings of a study that investigated the relationship between student involvement inextracurricular activities facilitated by ActivateUTS and the development of graduateattributes.

Darcy, S, Porto, N, Ruccia, AC, Garberoc, N & Almond, B 2019, 'Critical elements in accessible tourism for destination competitiveness & comparison: Principal component analysis from Oceania & South America'.
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This research sought to construct an exploratory nationally comparative tourism accessibility measure (TAI) through developing an objective set of metrics in the spirit and intent of the international treaties and missions regarding the rights of persons with disabilities.

Impellizzeri, FM, Wookcock, S, McCall, A, Ward, P & Coutts, AJ 2019, 'The acute-chronic workload ratio-injury figure and its ‘sweet spot’ are flawed', Center for Open Science.
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Kaasalainen, S, Sussman, T, Thompson, G, McCleary, L, Hunter, P, Venturato, L, Wickson-Griffiths, A, Ploeg, J, Parker, D, Sinclair, S, Haas, VD-B, Earl, M & You, J 2019, 'A Pilot Evaluation of the Strengthening a Palliative Approach in Long-Term Care (SPA-LTC) Program', Research Square Platform LLC.
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Kaasalainen, S, Sussman, T, Thompson, G, McCleary, L, Hunter, P, Wickson-Griffiths, A, Venturato, L, Ploeg, J, Parker, D, Sinclair, S, Haas, VD-B, Earl, M & You, J 2019, 'Evaluation of a Program Based on the Strengthening a Palliative Approach in Long-Term Care (SPA-LTC) Model', Research Square Platform LLC.
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Miller, R, Iancu, C, Babineau, J & Newton-John, T 2019, 'Are residential rehabilitation clients representative of Australians who engage in problematic Alcohol and Other Drug use?'.

Wang, B, Chan, YL, Zhou, S, Saad, S, Chen, H & Oliver, BG 2019, 'Offspring sex affects the susceptibility to maternal smoking-induced lung inflammation and the effect of maternal antioxidant supplementation in mice', Research Square Platform LLC.
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