Aboulkheyr Es, H, Zhand, S, Thiery, JP & Warkiani, ME 2020, 'Pirfenidone reduces immune-suppressive capacity of cancer-associated fibroblasts through targeting CCL17 and TNF-beta', Integrative Biology, vol. 12, no. 7, pp. 188-197.
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Abstract Various factors in the tumor microenvironment (TME) regulate the expression of PD-L1 in carcinoma cells. The cancer-associated fibroblasts (CAFs) play a crucial role in regulating and rewiring TME to enhance their immune suppressive function and to favor the invasion of the malignant cells. Tumor progression may be retarded by targeting CAFs in the TME. Various studies highlighted the ability of targeting CAF with pirfenidone (PFD), leading to increased efficacy of chemotherapy. However, its potential for the reduction of immune-suppression capacity of CAFs remains to be elusive. Here, we assessed the effect of PFD on the expression of PD-L1 on CAF cells. Besides migration inhibitory effects of PFD on CAFs, the expression level of PD-L1 reduced in CAFs after treatment with PFD. The downstream analysis of released cytokines from CAFs showed that PFD significantly dropped the secretion of CCL17 and TNF-β, where a positive association between PFD-targeted proteins and PD-L1 was observed. These data suggest that the treatment of CAF within TME through the PFD may reduce the acquisition of CAF-mediated invasive and immune-suppressive capacity of breast carcinoma cells.
Akyol, S, Akgun, MY, Yetmez, M, Hanci, M, Oktar, FN & Ben-Nissan, B 2020, 'Comparative Analysis of NF-κB in the MyD88-Mediated Pathway After Implantation of Titanium Alloy and Stainless Steel and the Role of Regulatory T Cells', World Neurosurgery, vol. 144, pp. e138-e148.
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OBJECTIVE: Development of immunologically smart implants, integrated to biological systems, is a key aim to minimize the inflammatory response of the host to biomaterial implants. METHODS: The aim of this study is to investigate the influence of titanium alloy and stainless steel implants on immunological responses in rats by comparative analysis of nuclear factor kappa B (NF-κB) profiles in the activation of inflammatory signaling pathways and the role of CD4+CD25+Foxp3+. RESULTS: Both Ti alloy and stainless steel alloy group implantation affect Toll-like receptors-4 pathways and CD4+CD25+ regulatory T cells in different ways. CONCLUSIONS: Results show that NF-κB/p65 and NF-κB1/p50 possess potential as a therapeutic target in the prevention of adverse reactions to metal, especially for controlling inflammation after the implantation.
Alghalayini, A, Jiang, L, Gu, X, Yeoh, GH, Cranfield, CG, Timchenko, V, Cornell, BA & Valenzuela, SM 2020, 'Real-time monitoring of heat transfer between gold nanoparticles and tethered bilayer lipid membranes', Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 1862, no. 9, pp. 183334-183334.
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Plasmon resonance frequency irradiated gold nanoparticles (GNPs) have gained interest as a laser-targeted treatment for infections, tumors and for the controlled release of drugs in situ. Questions still remain, however, as to the efficiency of heat delivery within biological tissues and how this can be reliably determined. Here, we demonstrate how a nanomaterial-electrode interface that mimics cell membranes can detect the localized heat transfer characteristics arising from plasmon resonance frequency-matched laser excitation of GNPs. We demonstrate that the lipid bilayer membrane can be affected by conjugated GNP induced hyperthermia when irradiated with a laser power output as low as 135 nW/μm2. This is four orders of magnitude lower power than previously reported. By restricting the lateral movement of the lipids in the bilayer membrane, it was shown that the change in membrane conductance as a result of the heat transfer was due to the creation of transient lipidic toroidal pores within the membrane. We further demonstrate that the heat transfer from the GNPs alters diffusion rates of monomers of the gramicidin-A peptide within the lipid leaflets. This work highlights how targeted low laser power GNP hyperthermia treatments, in vivo, could play a dual role of interfering with both cell membrane morphology and dynamics, along with membrane protein function.
Alghalayini, A, Jiang, L, Gu, X, Yeoh, GH, Cranfield, CG, Timchenko, V, Cornell, BA & Valenzuela, SM 2020, 'Tethered Bilayer Lipid Membranes to Monitor Heat Transfer between Gold Nanoparticles and Lipid Membranes', Journal of Visualized Experiments, no. 166.
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Ali, MK, Kim, RY, Brown, AC, Donovan, C, Vanka, KS, Mayall, JR, Liu, G, Pillar, AL, Jones‐Freeman, B, Xenaki, D, Borghuis, T, Karim, R, Pinkerton, JW, Aryal, R, Heidari, M, Martin, KL, Burgess, JK, Oliver, BG, Trinder, D, Johnstone, DM, Milward, EA, Hansbro, PM & Horvat, JC 2020, 'Critical role for iron accumulation in the pathogenesis of fibrotic lung disease', The Journal of Pathology, vol. 251, no. 1, pp. 49-62.
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AbstractIncreased iron levels and dysregulated iron homeostasis, or both, occur in several lung diseases. Here, the effects of iron accumulation on the pathogenesis of pulmonary fibrosis and associated lung function decline was investigated using a combination of murine models of iron overload and bleomycin‐induced pulmonary fibrosis, primary human lung fibroblasts treated with iron, and histological samples from patients with or without idiopathic pulmonary fibrosis (IPF). Iron levels are significantly increased in iron overloaded transferrin receptor 2 (Tfr2) mutant mice and homeostatic iron regulator (Hfe) gene–deficient mice and this is associated with increases in airway fibrosis and reduced lung function. Furthermore, fibrosis and lung function decline are associated with pulmonary iron accumulation in bleomycin‐induced pulmonary fibrosis. In addition, we show that iron accumulation is increased in lung sections from patients with IPF and that human lung fibroblasts show greater proliferation and cytokine and extracellular matrix responses when exposed to increased iron levels. Significantly, we show that intranasal treatment with the iron chelator, deferoxamine (DFO), from the time when pulmonary iron levels accumulate, prevents airway fibrosis and decline in lung function in experimental pulmonary fibrosis. Pulmonary fibrosis is associated with an increase in Tfr1+ macrophages that display altered phenotype in disease, and DFO treatment modified the abundance of these cells. These experimental and clinical data demonstrate that increased accumulation of pulmonary iron plays a key role in the pathogenesis of pulmonary fibrosis and lung function decline. Furthermore, these data highlight the potential for the therapeutic targeting of increased pulmonary iron in the treatment of fibrotic lung diseases such as IPF. © 2020 Pathological Society ...
Ali, MK, Kim, RY, Brown, AC, Mayall, JR, Karim, R, Pinkerton, JW, Liu, G, Martin, KL, Starkey, MR, Pillar, AL, Donovan, C, Pathinayake, PS, Carroll, OR, Trinder, D, Tay, HL, Badi, YE, Kermani, NZ, Guo, Y-K, Aryal, R, Mumby, S, Pavlidis, S, Adcock, IM, Weaver, J, Xenaki, D, Oliver, BG, Holliday, EG, Foster, PS, Wark, PA, Johnstone, DM, Milward, EA, Hansbro, PM & Horvat, JC 2020, 'Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma', European Respiratory Journal, vol. 55, no. 4, pp. 1901340-1901340.
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Accumulating evidence highlights links between iron regulation and respiratory disease. Here, we assessed the relationship between iron levels and regulatory responses in clinical and experimental asthma.We show that cell-free iron levels are reduced in the bronchoalveolar lavage (BAL) supernatant of severe or mild–moderate asthma patients and correlate with lower forced expiratory volume in 1 s (FEV1). Conversely, iron-loaded cell numbers were increased in BAL in these patients and with lower FEV1/forced vital capacity (FVC) ratio. The airway tissue expression of the iron sequestration molecules divalent metal transporter 1 (DMT1) and transferrin receptor 1 (TFR1) are increased in asthma, with TFR1 expression correlating with reduced lung function and increased Type-2 (T2) inflammatory responses in the airways. Furthermore, pulmonary iron levels are increased in a house dust mite (HDM)-induced model of experimental asthma in association with augmented Tfr1 expression in airway tissue, similar to human disease. We show that macrophages are the predominant source of increased Tfr1 and Tfr1+ macrophages have increased Il13 expression. We also show that increased iron levels induce increased pro-inflammatory cytokine and/or extracellular matrix (ECM) responses in human airway smooth muscle (ASM) cells and fibroblasts ex vivo and induce key features of asthma in vivo, including airway hyper-responsiveness (AHR) and fibrosis, and T2 inflammatory responses.Together these complementary clinical and experimental data highlight the importance of altered pulmonary iron levels and regulation in asthma, and the need for a greater focus on the role and potential therapeutic tar...
Amin, DB, Tavakoli, J, Freeman, BJC & Costi, JJ 2020, 'Mechanisms of Failure Following Simulated Repetitive Lifting', Spine, vol. 45, no. 6, pp. 357-367.
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Study Design. A biomechanical analysis correlating internal disc strains and tissue damage during simulated repetitive lifting. Objective. To understand the failure modes during simulated safe and unsafe repetitive lifting. Summary of Background Data. Repetitive lifting has been shown to lead to lumbar disc herniation (LDH). In vitro studies have developed a qualitative understanding of the effect of repetitive loading on LDH. However, no studies have measured internal disc strains and subsequently correlated these with disc damage. Methods. Thirty human cadaver lumbar functional spinal units were subjected to an equivalent of 1 year of simulated repetitive lifting under safe and unsafe levels of compression, in combination with flexion (13–15°), and right axial rotation (2°) for 20,000 cycles or until failure. Safe or unsafe lifting were applied as a compressive load to mimic holding a 20 kg weight either close to, or at arm's length, from the body, respectively. Maximum shear strains (MSS) were measured, and disc damage scores were determined in nine regions from axial post-test magnetic resonance imaging (MRI) and macroscopic images. Results. Twenty percent of specimens in the safe lifting group failed before 20,000 cycles due to endplate failure, compared with 67% in the unsafe group. Over half of the specimens in the safe lifting group failed via either disc protrusion or LDH, compared with only 20% via protrusion ...
Ariawan, AD, Sun, B, Wojciechowski, JP, Lin, I, Du, EY, Goodchild, SC, Cranfield, CG, Ittner, LM, Thordarson, P & Martin, AD 2020, 'Effect of polar amino acid incorporation on Fmoc-diphenylalanine-based tetrapeptides', Soft Matter, vol. 16, no. 20, pp. 4800-4805.
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The incorporation of polar amino acids into the Fmoc-FF motif yields tetrapeptide hydrogels whose biocompatibility in the gel state is inversely proportional to their biocompatibility in the solution state.
Asadniaye Fardjahromi, M, Razmjou, A, Vesey, G, Ejeian, F, Banerjee, B, Chandra Mukhopadhyay, S & Ebrahimi Warkiani, M 2020, 'Mussel inspired ZIF8 microcarriers: a new approach for large-scale production of stem cells', RSC Advances, vol. 10, no. 34, pp. 20118-20128.
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Mussel inspired ZIF8 microcarriers with high surface area, biocompatibility, and nanoscale surface roughness are applied to enhance mesenchymal stem cell attachment and proliferation in 3D cell culture.
Asano, R, Mathai, SC, Macdonald, PS, Newton, PJ, Currow, DC, Phillips, J, Yeung, W-F & Davidson, PM 2020, 'Oxygen use in chronic heart failure to relieve breathlessness: A systematic review', Heart Failure Reviews, vol. 25, no. 2, pp. 195-205.
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To appraise published studies on the use of supplemental oxygen in chronic heart failure. Chronic breathlessness is a characterizing symptom of symptomatic heart failure resulting in substantial disability and healthcare utilization and is the primary reason for emergency room visits and hospitalizations. In spite of the variable evidence, oxygen therapy is commonly administered both acutely and chronically. Moreover, the role of oxygen therapy to relieve chronic breathlessness in heart failure is not well described, particularly in normoxemic or mild or intermittent hypoxemic states. In fact, several studies have shown the detrimental effects of oxygen therapy with normal oxygen saturation levels. A systematic review using PRISMA guidelines. Four databases PubMed, Embase, CINAHL, and Web of Science were systematically searched from January 2001 to January 2019 investigating the use of oxygen in heart failure. Duplicate articles were removed from the review. Titles and abstracts were screened for inclusion and exclusion criteria. The remaining full-text articles were reviewed and hand-searched for additional references. The quality of the full-text articles was assessed using standardized critical appraisal instruments by the Joanna Briggs Institute. A total of 11 studies, including three intervention and eight non-interventions studies, were included in this review from 1072 non-duplicated records retrieved. Sample size ranged from 4 to 5862. In spite of common usage, this review suggests that there are scant data available to justify the use of oxygen in individuals with non-hypoxemic chronic heart failure and chronic breathlessness.
Asano, R, Newton, PJ, Currow, DC, Macdonald, PS, Leung, D, Phillips, JL, Perrin, N & Davidson, PM 2020, 'Reply to Kako, Kajiwara, Kobayashi, and Oosono letter to the editor response', Heart Failure Reviews, vol. 25, no. 5, pp. 893-893.
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Azadi, S, Aboulkheyr Es, H, Kulasinghe, A, Bordhan, P & Ebrahimi Warkiani, M 2020, 'Application of microfluidic technology in cancer research and therapy', Advances in Clinical Chemistry, vol. 99, pp. 193-235.
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Cancer is a heterogeneous disease that requires a multimodal approach to diagnose, manage and treat. A better understanding of the disease biology can lead to identification of novel diagnostic/prognostic biomarkers and the discovery of the novel therapeutics with the goal of improving patient outcomes. Employing advanced technologies can facilitate this, enabling better diagnostic and treatment for cancer patients. In this regard, microfluidic technology has emerged as a promising tool in the studies of cancer, including single cancer cell analysis, modeling angiogenesis and metastasis, drug screening and liquid biopsy. Microfluidic technologies have opened new ways to study tumors in the preclinical and clinical settings. In this chapter, we highlight novel application of this technology in area of fundamental, translational and clinical cancer research.
Bajan, S & Hutvagner, G 2020, 'RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs', Cells, vol. 9, no. 1, pp. 137-137.
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The first therapeutic nucleic acid, a DNA oligonucleotide, was approved for clinical use in 1998. Twenty years later, in 2018, the first therapeutic RNA-based oligonucleotide was United States Food and Drug Administration (FDA) approved. This promises to be a rapidly expanding market, as many emerging biopharmaceutical companies are developing RNA interference (RNAi)-based, and RNA-based antisense oligonucleotide therapies. However, miRNA therapeutics are noticeably absent. miRNAs are regulatory RNAs that regulate gene expression. In disease states, the expression of many miRNAs is measurably altered. The potential of miRNAs as therapies and therapeutic targets has long been discussed and in the context of a wide variety of infections and diseases. Despite the great number of studies identifying miRNAs as potential therapeutic targets, only a handful of miRNA-targeting drugs (mimics or inhibitors) have entered clinical trials. In this review, we will discuss whether the investment in finding potential miRNA therapeutic targets has yielded feasible and practicable results, the benefits and obstacles of miRNAs as therapeutic targets, and the potential future of the field.
Beehan-Quirk, C, Jarman, L, Maharaj, S, Simpson, A, Nassif, N & Lal, S 2020, 'Investigating the effects of fatigue on blood glucose levels – Implications for diabetes', Translational Metabolic Syndrome Research, vol. 3, pp. 17-20.
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Bennett, KJM, Novak, AR, Pluss, MA, Coutts, AJ & Fransen, J 2020, 'A multifactorial comparison of Australian youth soccer players’ performance characteristics', International Journal of Sports Science & Coaching, vol. 15, no. 1, pp. 17-25.
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The current study aimed to investigate the performance characteristics that discriminate Australian youth soccer players according to their academy status. A total of 165 youth soccer players participated in this study and were sub-divided into either an early adolescence ( n = 92, age = 13.0 ± 0.6 years) or mid-adolescence ( n = 73 age = 14.8 ± 0.6 years) group. Players completed multifactorial assessments of anthropometry, motor competence, physical fitness, decision-making and psychological traits. Statistical significance was set at p ≤ 0.05. Multivariate analysis of variance identified dynamic balancing ability (both age groups), object manipulation (mid-adolescence), lateral jumping ability (both age groups), linear speed over 5 m (both age groups), change of direction skill (mid-adolescence), intermittent aerobic endurance (mid-adolescence) and total response time on a decision-making assessment (early adolescence) to discriminate academy status. Interestingly, a binomial logistical regression showed that a 0.1 s decrease in sprint time (i.e. running faster) increased the odds of a player belonging to a tier one academy by 19% and 47% for early and mid-adolescent players, respectively. Overall, performance in the motor competence and physical fitness assessments were in favour of the tier one academy players. These findings are indicative of a potential selection bias in the Australian talent pool or a training effect whereby tier one academy programmes emphasise the development of physical attributes. However, future research is required to further substantiate this in a larger sample of youth soccer players from other playing regions within Australia.
Ben-Nissan, I, Ueland, M, Taudte, V, Ben-Nissan, B & Zaslawski, C 2020, 'Is moxibustion safe? An analytic chemical analysis of moxa smoke', Integrative Medicine Research, vol. 9, pp. 100549-100549.
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Bhattarai, P, Newton-John, T & Phillips, JL 2020, 'Apps for Older People’s Pain Self-Management: Perspectives of Primary Care and Allied Health Clinicians', Pain Medicine, vol. 21, no. 4, pp. 686-694.
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Abstract Background Chronic arthritic pain is one of the major causes of physical suffering and disability among older people. Primary care and allied health clinicians use various approaches to help their older clients better manage their arthritic pain. The growing uptake of technology among older people offers the potential for clinicians to integrate an arthritic pain app into their patients’ self-management plans. This study explored the perspectives of Australian primary care and allied health clinicians regarding the use of pain self-management apps to help their older patients/clients better manage their arthritic pain. Methods Qualitative design using a semistructured interview approach. Interviews were conducted via telephone with primary and allied health clinicians (N = 17) across Australia. Results The overarching theme underlying participants’ views on integration of apps into older people’s pain self-management strategy was that this approach is an idealistic but uniquely challenging endeavor. Four subthemes emerged, namely: 1) self-management apps are a potentially useful tool but require careful consideration; 2) clinicians’ involvement is crucial yet potentially onerous; 3) no single app is right for every older person with arthritic pain; and 4) patient data access is beneficial, but caution is needed for real-time data access. Discussion The predominant clinician perspective of integrating apps into their older patients/clients’ p...
Bhattarai, P, Newton-John, TRO & Phillips, JL 2020, 'Apps for pain self-management of older people’s arthritic pain, one size doesn’t fit all: A qualitative study', Archives of Gerontology and Geriatrics, vol. 89, pp. 104062-104062.
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Introduction Arthritic pain is a major cause of illness and disability among older people. People living with arthritic pain carry out self-management activities to adequately manage their pain. As the trend of smartphone uptake continues to rise among older people, there are opportunities to explore the role of these devices in helping older people better manage their pain. Aim: To explore the attitudes and experiences of older people with chronic arthritic pain towards using an app for their pain selfmanagement. Methods A qualitative design using semi-structured interviews with community-dwelling older Australians living with arthritic pain (n = 16). Data was analyzed using thematic analysis. Results Four themes emerged from the data: (1) Apps are valuable self-management tool, but they do have the potential for harm; (2) A pain self-management app needs to strictly align with the user's needs; (3) Clinician's involvement is crucial when integrating an app into older people's pain selfmanagement regime; and (4) pain self-management app must be designed with enduser in mind. In addition, suggestions on how to make an app more useful and userfriendly were offered by the participants. Discussion While pain self-management apps have the potential to assist older people in their pain self-management process, this modality is not of interest to all older people. Adaptable apps that offer clinician input may be best placed to offer individual level relevance to older users. Future pain selfmanagement app development endeavors should adopt a co-design approach where older people are involved through all stages of design and development.
Blazevski, A, Scheltema, MJ, Yuen, B, Masand, N, Nguyen, TV, Delprado, W, Shnier, R, Haynes, A-M, Cusick, T, Thompson, J & Stricker, P 2020, 'Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort', European Urology Oncology, vol. 3, no. 3, pp. 283-290.
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BACKGROUND:Focal irreversible electroporation (IRE) can be used to treat men with localised prostate cancer (PCa) with reduced impact on quality of life (QoL). OBJECTIVE:To assess oncological and functional outcomes. DESIGN, SETTING, AND PARTICIPANTS:To report on a prospective database of patients undergoing primary IRE between February 2013 and August 2018. A minimum of 12-mo follow-up was available for 123 patients. Median follow-up was 36 mo (interquartile range [IQR] 24-52 mo). A total of 112 (91%) patients had National Comprehensive Cancer Network intermediate risk and 11 (9%) had low risk. A total of 12 (9.8%) had International Society of Urological Pathology (ISUP) grade 1, 88 (71.5%) had ISUP 2, and 23 (18.7%) had ISUP 3. INTERVENTION:Focal IRE ablation of PCa lesions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Follow-up involved serial prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and transperineal template mapping biopsy (TTMB) at 12 mo. Failure-free survival (FFS) was defined as progression to whole-gland or systemic treatment or metastasis/death. Functional outcomes were assessed. RESULTS AND LIMITATIONS:Median age was 68yr (IQR 62-73yr). Median preoperative PSA was 5.7ng/ml (IQR 3.8-8.0ng/ml). On post-treatment TTMB, in-field recurrence was present in 2.7-9.8% of patients. FFS at 3yr was 96.75%, metastasis-free survival 99%, and overall survival 100%. A total of 18 patients required salvage treatment (12 had repeat IRE; six had whole-gland treatment). The negative predictive value of mpMRI was 94% and sensitivity 40% for detecting in-field residual disease 6 mo after treatment. Among patients who returned questionnaires, 80/81 (98.8%) remained pad free and 40/53 (76%) had no change in erectile function. CONCLUSIONS:Focal IRE in select patients with localised clinically significant PCa has satisfactory short-term oncological outcomes with a minimal impact on patient QoL. PATIENT SUMMARY:In this study...
Bliuc, D, Tran, T, Adachi, JD, Atkins, GJ, Berger, C, van den Bergh, J, Cappai, R, Eisman, JA, van Geel, T, Geusens, P, Goltzman, D, Hanley, DA, Josse, R, Kaiser, S, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV, Solomon, LB, Stapledon, C & Center, JR 2020, 'Reply to: The Association Between Cognitive Decline and Bone Loss and Fracture Risk Is Not Affected by Medication With Anticholinergic Effect', Journal of Bone and Mineral Research, vol. 37, no. 5, pp. 1075-1076.
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Bousquet, J, Anto, JM, Iaccarino, G, Czarlewski, W, Haahtela, T, Anto, A, Akdis, CA, Blain, H, Canonica, GW, Cardona, V, Cruz, AA, Illario, M, Ivancevich, JC, Jutel, M, Klimek, L, Kuna, P, Laune, D, Larenas-Linnemann, D, Mullol, J, Papadopoulos, NG, Pfaar, O, Samolinski, B, Valiulis, A, Yorgancioglu, A & Zuberbier, T 2020, 'Is diet partly responsible for differences in COVID-19 death rates between and within countries?', Clinical and Translational Allergy, vol. 10, no. 1.
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AbstractReported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.
Bousquet, J, Cristol, J-P, Czarlewski, W, Anto, JM, Martineau, A, Haahtela, T, Fonseca, SC, Iaccarino, G, Blain, H, Fiocchi, A, Canonica, GW, Fonseca, JA, Vidal, A, Choi, H-J, Kim, HJ, Le Moing, V, Reynes, J, Sheikh, A, Akdis, CA & Zuberbier, T 2020, 'Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies', Clinical and Translational Allergy, vol. 10, no. 1, p. 58.
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AbstractThere are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Bozier, J, Zakarya, R, Chapman, DG & Oliver, BGG 2020, 'How harmless are E-cigarettes? Effects in the pulmonary system', Current Opinion in Pulmonary Medicine, vol. 26, no. 1, pp. 97-102.
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Purpose of review Electronic cigarettes have quickly risen to be the leading alternative nicotine source to tobacco. E-cigarette use is hard to research and regulate because of the novelty and rapid evolution of the devices and E-liquids. Epidemiological data on long-term usage is currently lacking, but in smaller cohort studies we are starting to understand the usage patterns and demographics of users, which differ depending on where the study takes place and the regulatory environment. The present review describes the current knowledge of the effects of E-cigarettes on the pulmonary system and knowledge of their usage patterns worldwide. Recent findings E-cigarette use is continuing to rise in young adults in United States and Canada, but not in United Kingdom. These suggest that regulation is influencing uptake in young adults. If E-cigarettes are to be considered as a harm minimisation smoking cessation product, use in young never smokers must be factored into the risk assessment. A recent surge in cases of lung injury associated with vaping in America has resulted in the definition of vaping associated pulmonary injury, although the exact cause remains unknown. Summary It is our opinion that E-cigarettes can no longer be defined as harmless. Further studies are needed to determine the risks for all populations as it is evident that a large proportion of E-cigarette users are never-smokers, meaning they cannot only be considered from a harm reduction perspective.
Brown, P, Ly, T, Pham, H & Sivabalan, P 2020, 'Automation and management control in dynamic environments: Managing organisational flexibility and energy efficiency in service sectors', The British Accounting Review, vol. 52, no. 2, pp. 100840-100840.
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Automation has been conceptually explained in management accounting research as an antecedent to control problem avoidance (Emmanuel, Merchant, & Otley, 1990). However, the question of how automation is implicated in more dynamic service-based environments remains unanswered. We apply the Adler and Borys' (1996) bureaucracy framework to explain how enabling controls allow organisations to simultaneously pursue organisational flexibility and energy efficiency (Ahrens & Chapman, 2004; Jorgensen & Messner, 2009). Subsequently, we examine how automation and its related management control are designed and used in a dynamic service-based organisation, where goal attainment and the energy efficiency of its buildings are critical. In doing so, we explain how automation-related standardisation is adjusted by enabling control attributes (repair, flexibility, internal transparency) to advance user flexibility. Additionally, standardisation minimises the loss in energy efficiency when less optimal repair control behaviour manifests. Our study adds more depth to the work by Merchant and Van de Stede (2017) by exploring how automation complements labour in dynamic environments. Our findings offer greater understanding of how automation and management control systems are designed and used to enhance organisations' energy efficiency in dynamic service-based environments. In doing so, we advance extant environmental management accounting studies (Virtanen, Tuomaala, & Pentti, 2013).
Cahill, PJ, Lobb, EA, Sanderson, CR & Phillips, JL 2020, '“Standing Shoulder to Shoulder to Tell the Family What Was Really Going On”: A Qualitative Study Exploring Palliative Care Clinicians' Perceptions of “Patient-Centered Family Meetings”', Journal of Palliative Medicine, vol. 23, no. 10, pp. 1307-1313.
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Callaghan, R, Gelissen, IC, George, AM & Hartz, AMS 2020, 'Mamma Mia, P‐glycoprotein binds again', FEBS Letters, vol. 594, no. 23, pp. 4076-4084.
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The levels of amyloid peptides in the brain are regulated by a clearance pathway from neurons to the blood–brain barrier. The first step is thought to involve diffusion from the plasma membrane to the interstitium. However, amyloid peptides are hydrophobic and avidly intercalate within membranes. The ABC transporter P‐glycoprotein is implicated in the clearance of amyloid peptides across the blood–brain, but its role at neurons is undetermined. We here propose that P‐glycoprotein mediates 'exit' of amyloid peptides from neurons. Indeed, amyloid peptides have physicochemical similarities to substrates of P‐glycoprotein, but their larger size represents a conundrum. This review probes the plausibility of a mechanism for amyloid peptide transport by P‐glycoprotein exploiting evolving biochemical and structural models.
Chalmers, T, Maharaj, S, Lees, T, Lin, CT, Newton, P, Clifton-Bligh, R, McLachlan, CS, Gustin, SM & Lal, S 2020, 'Impact of acute stress on cortical electrical activity and cardiac autonomic coupling', Journal of Integrative Neuroscience, vol. 19, no. 2, pp. 239-239.
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Assessment of heart rate variability (reflective of the cardiac autonomic nervous system) has shown some predictive power for stress. Further, the predictive power of the distinct patterns of cortical brain activity and - cardiac autonomic interactions are yet to be explored in the context of acute stress, as assessed by an electrocardiogram and electroencephalogram. The present study identified distinct patterns of neural-cardiac autonomic coupling during both resting and acute stress states. In particular, during the stress task, frontal delta waves activity was positively associated with low-frequency heart rate variability and negatively associated with high-frequency heart rate variability. Low high-frequency power is associated with stress and anxiety and reduced vagal control. A positive association between resting high-frequency heart rate variability and frontocentral gamma activity was found, with a direct inverse relationship of low-frequency heart rate variability and gamma wave coupling at rest. During the stress task, low-frequency heart rate variability was positively associated with frontal delta activity. That is, the parasympathetic nervous system is reduced during a stress task, whereas frontal delta wave activity is increased. Our findings suggest an association between cardiac parasympathetic nervous system activity and frontocentral gamma and delta activity at rest and during acute stress. This suggests that parasympathetic activity is decreased during acute stress, and this is coupled with neuronal cortical prefrontal activity. The distinct patterns of neural-cardiac coupling identified in this study provide a unique insight into the dynamic associations between brain and heart function during both resting and acute stress states.
Chamoli, U, Umali, J, Kleuskens, MWA, Chepurin, D & Diwan, AD 2020, 'Morphological characteristics of the kangaroo lumbar intervertebral discs and comparison with other animal models used in spine research', European Spine Journal, vol. 29, no. 4, pp. 652-662.
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PURPOSE:Animal models are frequently used to elucidate pathomechanism and pathophysiology of various disorders of the human intervertebral disc (IVD) and also to develop therapeutic approaches. Here we report morphological characteristics of the kangaroo lumbar IVDs and compare them with other animal models used in spine research. METHODS:Twenty-five fresh-frozen cadaveric lumbar spines (T12-S1) derived from kangaroo carcases (Macropus giganteus) of undetermined age were first scanned in a C-Arm X-ray machine. A photograph of the axial section of the disc including a calibrated metric scale was also acquired. The digital radiographs and photographs were processed in ImageJ to determine the axial and sagittal plane dimensions for the whole disc (WD) and the nucleus pulposus (NP) and the mid-sagittal disc height for all the lumbar levels. RESULTS:Our results suggest that the L6-S1 IVD in kangaroos is distinctly large compared with the upper lumbar IVDs. Based on previously published data, human lumbar IVDs are the largest of all the animal IVDs used in spine research, with camelid cervical IVDs being the closest relative in absolute dimensions (llamas: 78% in disc height, 40% in WD volume, and 38% in NP volume). Kangaroo L6-S1 IVD was approximately 51% in height, 20% in WD volume, and 20% in NP volume of the human lumbar IVD. CONCLUSIONS:We conclude that morphological similarities exist between a kangaroo and human lumbar IVD, especially with the lima bean shape in the axial plane, wedge shape in the sagittal plane, convexity at the cephalad endplates, and percentage volume occupied by the NP in the IVD. These slides can be retrieved under Electronic Supplementary Material.
Chan, YL, Oliver, BG & Chen, H 2020, 'What lessons have we learnt about the impact of maternal cigarette smoking from animal models?', Clinical and Experimental Pharmacology and Physiology, vol. 47, no. 2, pp. 337-344.
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AbstractMaternal first‐ or second‐hand tobacco smoking during pregnancy is still common albeit that the detrimental effects to the unborn child are well known. Maternal tobacco cigarette smoking can affect multiple organ systems in the offspring, rendering them at increased risk of various conditions throughout life (eg. intrauterine underdevelopment, asthma, substance abuse, diabetes). However, this review will only focus on its impact on the brain and the related molecular changes in the offspring based on evidence from animal studies. Although epidemiological studies have identified the associations between maternal cigarette smoke exposure (SE) and brain disorders, animal models can help identify the underlying mechanisms and test interventions. Human studies have found that maternal SE is closely linked to small brain size and changes in brain structure and associated with a high risk of cognitive defects. Animal models suggest that this may be due to increased brain oxidative stress and inflammation during the neonatal period, leading to increased brain cell apoptosis in adulthood. There is a distinct gender bias of such impacts, where male offspring are more affected than females. Female offspring seem to have developed the adaptation by increasing endogenous antioxidant levels. Indeed, animal studies have shown that using antioxidant supplementation during pregnancy can improve neurological outcomes in male offspring, however, the efficacy in humans is yet to be confirmed. Furthermore, some animal studies suggested nicotine as the key player in intrauterine underdevelopment due to maternal SE, while human clinical trials using nicotine replacement therapy do not support this mechanism. This review will discuss the possible reasons.
Chandran, M, Bhadada, SK, Ebeling, PR, Gilchrist, NL, Khan, AH, Halbout, P, Lekamwasam, S, Lyubomirsky, G, Mitchell, PJ, Nguyen, TV & Tiu, KL 2020, 'IQ driving QI: the Asia Pacific Consortium on Osteoporosis (APCO): an innovative and collaborative initiative to improve osteoporosis care in the Asia Pacific', Osteoporosis International, vol. 31, no. 11, pp. 2077-2081.
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Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region.
Introduction
The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis and fragility fractures in the AP region.
Methods
APCO has so far brought together 39 clinical experts from countries and regions across the AP to develop solutions to challenges facing osteoporosis management and fracture prevention in this highly populous region of the world. APCO aims to achieve its vision by engaging with relevant stakeholders including healthcare providers, policy makers and the public. The initial APCO project is to develop and implement a Framework of pan-AP minimum clinical standards for the screening, diagnosis and management of osteoporosis.
Results and conclusions
The Framework will serve as a platform upon which new national clinical guidelines can be developed or existing guidelines be revised, in a standardised fashion. The Framework will also facilitate benchmarking for provision of quality of care. It is hoped that the principles underlying the formation and functioning of APCO can be adopted by other regions and that every health care facility and progressively every country in the world can follow our aspirational path and progress towards best practice.
Chandran, M, Ebeling, PR, Mitchell, PJ & Nguyen, TV 2020, 'Harmonization of Osteoporosis Guidelines: Paving the Way for Disrupting the Status Quo in Osteoporosis Management in the Asia Pacific', Journal of Bone and Mineral Research, vol. 37, no. 4, pp. 608-615.
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ABSTRACT In the Asia Pacific (AP) region, osteoporosis and its consequence of fragility fractures are not widely recognized as a major public health problem. Several challenges including underdiagnosis and undertreatment exist. The Asia Pacific Consortium on Osteoporosis (APCO) is a nonpartisan and apolitical organization comprising musculoskeletal experts and stakeholders from both private and public sectors who have united to develop tangible solutions for these substantive challenges. APCO's vision is to reduce the burden of osteoporosis and fragility fractures in the AP region. Heterogeneity in both scope and recommendations among the available clinical practice guidelines (CPGs) contribute to the large osteoporosis treatment gap in the Asia Pacific. APCO has therefore developed a pan Asia-Oceania harmonized set of standards of care (The Framework), for the screening, diagnosis, and management of osteoporosis. First, a structured analysis of the 18 extant AP CPGs was completed. Subsequently, a prioritization of themes and agreement on fundamental principles in osteoporosis management were made through a Delphi process of consensus building. This approach, ensuring the opinions of all participating members were equally considered, was especially useful for a geographically diverse group such as APCO. It is hoped that the Framework will serve as a platform upon which new AP national CPGs can be developed and existing ones be revised. APCO is currently embarking on country-specific engagement plans to embed the Framework in clinical practice in the AP region. This is through partnering with regulatory bodies and national guidelines development authorities, through peer-to-peer health care professional education and by conducting path finder audits to benchmark current osteoporosis services against the Framework standards. The principles underpinning the harmonization of guidelines in the AP region can als...
Changani, Z, Razmjou, A, Taheri-Kafrani, A, Warkiani, ME & Asadnia, M 2020, 'Surface modification of polypropylene membrane for the removal of iodine using polydopamine chemistry', Chemosphere, vol. 249, pp. 126079-126079.
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The development of stable and effective iodine removal systems would be highly desirable in addressing environmental issues relevant to water contamination. In the present research, a novel iodine adsorbent was synthesized by self-polymerization of dopamine (PDA) onto inert polypropylene (PP) membrane. This PP/PDA membrane was thoroughly characterized and its susrface propeties was analyzed by various analytical techniques indcluding field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH), contact angle, and surface free energy measurement. The PP/PDA membranes were subsequently used for batchwise removal of iodine at different temperatures (25-70 °C), pH (2-7), and surface areas (1-10 cm2) to understand the underlying adsorption phenomena and to estimate the membrane capacity for iodine uptake. The increase in temperature and pH both led to higher adsorption of iodine. The present approach showed a removal efficiency of over 75% for iodine using 10 cm2 PP/PDA membrane (18.87 m2 g-1) within 2 h at moderate temperatures (∼50 °C) and pH > 4, about 15 fold compared to the PP control membrane. The adsorption kinetics and isotherms were well fitted to the pseudo-second-order kinetic and Langmuir isotherm models (R2 > 0.99). This adsorbent can be recycled and reused at least six times with stable iodine adsorption. These findings were attributed to the homogenous monolayer adsorption of the iodide on the surface due to the presence of catechol and amine groups in the PP/PDA membrane. This study proposes an efficient adsorbent for iodine removal.
Chehade, M, Bullock, M, Glover, A, Hutvagner, G & Sidhu, S 2020, 'Key MicroRNA’s and Their Targetome in Adrenocortical Cancer', Cancers, vol. 12, no. 8, pp. 2198-2198.
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Adrenocortical Carcinoma (ACC) is a rare but aggressive malignancy with poor prognosis and limited response to available systemic therapies. Although complete surgical resection gives the best chance for long-term survival, ACC has a two-year recurrence rate of 50%, which poses a therapeutic challenge. High throughput analyses focused on characterizing the molecular signature of ACC have revealed specific micro-RNAs (miRNAs) that are associated with aggressive tumor phenotypes. MiRNAs are small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation or degrading mRNA transcripts and have been generally implicated in carcinogenesis. This review summarizes the current insights into dysregulated miRNAs in ACC tumorigenesis, their known functions, and specific targetomes. In addition, we explore the possibility of particular miRNAs to be exploited as clinical biomarkers in ACC and as potential therapeutics.
Chen, H, Li, G, Allam, VSRR, Wang, B, Chan, YL, Scarfo, C, Ueland, M, Shimmon, R, Fu, S, Foster, P & Oliver, BG 2020, 'Evidence from a mouse model on the dangers of thirdhand electronic cigarette exposure during early life', ERJ Open Research, vol. 6, no. 2, pp. 00022-2020.
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Thirdhand exposure to e-cigarette residue is likely to have harmful effects in children http://bit.ly/38a2umw.
Chen, H, McGrath, K, Rayner, B & McClements, L 2020, '054 Potential New Treatment Based on FKBPL for Hypertension-Induced Cardiac Hypertrophy', Heart, Lung and Circulation, vol. 29, pp. S62-S62.
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Chen, H, Power, T, Hayes, C, Reyna, J & van Reyk, D 2020, 'Perceptions of Video Scenarios to Learn Human Pathophysiology Among Undergraduate Science Students', Journal of Science Education and Technology, vol. 29, no. 5, pp. 597-604.
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© 2020, Springer Nature B.V. Pathophysiology describes and explains the physiological dysfunctions that occur in human diseases. Pathophysiology is content heavy, often leading to medical/biomedical science students adopting a surface approach to learning. To encourage more engagement, we developed clinical simulation practical classes using manikin patients. Students considered these were more effective than paper-based case studies. However, they found the first encounter with the manikins daunting. In addition, they did not have a strong sense of responsibility towards the outcome of their treatment choices largely because they recognized this as a simulated experience. Video is a powerful teaching tool to demonstrate situations that are difficult to explain in words, to see theory applied to practice or create enthusiasm and confidence in the viewer regarding the use of new practices. In this study, we evaluated the effectiveness of exposure to a video scenario, in which a high-fidelity manikin was used as the ‘patient’, before the students’ own interactions with the manikin in later classes. Survey results suggested that the students felt more engaged with the case study. They felt the video helped them appreciate aspects of clinical communication and prepare for their time in the simulation laboratory interacting with the manikin. They saw the video as a useful addition to the written case study notes. Their criticisms were mainly around the production quality. This study supports the use of video scenarios as a valuable adjunct to the teaching of pathophysiology to medical/biomedical science students when using either paper- or simulation-based case studies.
Chen, X, Chamoli, U, Vargas Castillo, J, Ramakrishna, VAS & Diwan, AD 2020, 'Complication rates of different discectomy techniques for symptomatic lumbar disc herniation: a systematic review and meta-analysis', European Spine Journal, vol. 29, no. 7, pp. 1752-1770.
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Chen, Y, Chen, H, Li, Y, Chen, Z, Wu, Y, McGowan, E, Qu, X, Lin, Y & Sun, B 2020, 'Chinese herbal medicine Guilu erxian jiao attenuates bone marrow suppression following chemotherapy in patients with advanced lung cancer', Translational Metabolic Syndrome Research, vol. 3, pp. 25-28.
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In recent decades, a classic recipe in traditional Chinese medicine, Guilu erxian jiao (GEJ), has been used in the prevention and treatment of myelosuppression following cancer chemotherapy. However, the safety and efficacy of GEJ has not been studied. In the present study, we investigated the safety and efficacy of GEJ in the management of myelosuppression in a cohort of advanced lung adenocarcinoma patients who received 4 cycles of chemotherapy. Treatment with GEJ was compared to the conventional treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF). The GEJ treatment group (38 patients) was orally administered GEJ whilst the control group (25 patients) were treated with PEG-rhG-CSF during the 4 cycles of chemotherapy. We found that GEJ was as safe as the recommended treatment, PEG-rhG-CSF . GEJ patients recovered from suppressed bone marrow in a much steadier approach, compared with the highly fluctuating changes observed in PEG-rhG-CSF treatment. Our data suggests that GEJ may be a better alternative to manage cancer chemotherapy-induced myelosuppression.
Chen, Y, D'Amario, C, Gee, A, Duong, HTT, Shimoni, O & Valenzuela, SM 2020, 'Dispersion stability and biocompatibility of four ligand-exchanged NaYF4: Yb, Er upconversion nanoparticles', Acta Biomaterialia, vol. 102, pp. 384-393.
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Surface modification to obtain high dispersion stability and biocompatibility is a key factor for bio-application of upconversion nanoparticles (UCNPs). A systematic study of UCNPs modified with four hydrophilic molecules separately, comparing their dispersion stability in biological buffers and cellular biocompatibility is reported here. The results show that carboxyl-functionalized UCNPs (modified by 3,4-dihydrocinnamic acid (DHCA) or poly(monoacryloxyethyl phosphate (MAEP)) with negative surface charge have superior even-distribution in biological buffers compared to amino-functionalized UCNPs (modified by (aminomethyl)phosphonic (AMPA) or (3-Aminopropyl)triethoxysilane (APTES)) with positive surface charge. Subsequent investigation of cellular interactions revealed high levels of non-targeted cellular uptake of the particles modified with either of the three small molecules (AMPA, APTES, DHCA) and high levels of cytotoxicity when used at high concentrations. The particles were seen to be trapped as particle-aggregates within the cellular cytoplasm, leading to reduced cell viability and cell proliferation, along with dysregulation of the cell cycle as assessed by DNA content measurements. The dramatically reduced proportion of cells in G1 phase and the slightly increased proportion in G2 phase indicates inhibition of M phase, and the appearance of sub-G1 phase reflects cell necrosis. In contrast, MAEP-modified UCNPs are bio-friendly with increased dispersion stability in biological buffers, are non-cytotoxic, with negligible levels of non-specific cellular uptake and no effect on the cell cycle at both low and high concentrations. MAEP-modified UCNPs were further functionalized with streptavidin for intracellular microtubule imaging, and showed clear cytoskeletal structures via their upconversion luminescence. STATEMENT OF SIGNIFICANCE: Upconversion nanoparticles (UCNP) are an exciting potential nanomaterial for bio-applications. Their anti-Stokes lu...
Cheng, J, Tan, Y, Zhou, J, Xiao, L, Johnson, M & Qu, X 2020, 'Green tea polyphenols ameliorate metabolic abnormalities and insulin resistance by enhancing insulin signalling in skeletal muscle of Zucker fatty rats', Clinical Science, vol. 134, no. 10, pp. 1167-1180.
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Abstract In the present study, we evaluated the metabolic effects of green tea polyphenols (GTPs) in high-fat diet (HFD) fed Zucker fatty (ZF) rats, in particular the effects of GTP on skeletal muscle insulin sensitivity. Body weight, visceral fat, glucose tolerance, lipid profiles and whole-body insulin sensitivity were measured in HFD-fed ZF rats after 8-week-treatment with GTP (200 mg/kg of body weight) or saline (5 ml/kg of body weight). Zucker lean rats were studied as controls. Ex vivo insulin-mediated muscle glucose uptake was assessed. Immunoblotting was used to evaluate the expression of key insulin signalling proteins in skeletal muscle. GTP treatment attenuated weight gain (P<0.05) and visceral fat accumulation (27.6%, P<0.05), and significantly reduced fasting serum glucose (P<0.05) and insulin (P<0.01) levels. Homoeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance, was lower (P<0.01) in GTP-treated animals compared with ZF controls. Moreover, insulin-stimulated glucose uptake by isolated soleus muscle was increased (P<0.05) in GTP-ZF rats compared with ZF-controls. GTP treatment attenuated the accumulation of ectopic lipids (triacyl- and diacyl-glycerols), enhanced the expression and translocation of glucose transporter-4, and decreased pSer612IRS-1 and increased pSer473Akt2 expression in skeletal muscle. These molecular changes were also associated with significantly decreased activation of the inhibitory (muscle-specific) protein kinase (PKC) isoform, PKC-θ. Taken together, the present study has shown that regular ingestion of GTP exerts a number of favourable metabolic and molecular effects in an established animal model of obesity and insulin resistance. The benefits of GTP are mediated in part by inhibiting PKC-θ and improving muscle insulin sensitivity.
Choi, AH, Karacan, I & Ben-Nissan, B 2020, 'Surface modifications of titanium alloy using nanobioceramic-based coatings to improve osseointegration: a review', Materials Technology, vol. 35, no. 11-12, pp. 742-751.
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© 2018 Informa UK Limited, trading as Taylor & Francis Group. Nanomaterials such as nanostructured scaffolds in tissue engineering and nanoparticles in drug delivery systems are associated with many applications within the biomedical and dental arenas. Furthermore, nanotechnology has also played an important role in the modifications of surface properties of surgical-grade materials and implants to achieve improvements in in vivo performance and reliability. The utilizations of nanocoatings, nanocomposite coatings, and nanolaminates are also intended to enhance osseointegration and improved protection from the release of unnecessary or even harmful metal ions. Due to their nanocrystalline structure and increase surface area, they become more reactive and hence they can also be synthesized to deliver faster tissue bonding properties and exceptional bioactivity. These new generation nanocoatings based on inorganic and biological materials such as proteins and peptides are currently being developed and investigated. This review aims to give an overview into the recent advances in nanocoatings containing biological materials being applied in medicine.
Choi, G, Choi, AH, Evans, LA, Akyol, S & Ben‐Nissan, B 2020, 'A review: Recent advances in sol‐gel‐derived hydroxyapatite nanocoatings for clinical applications', Journal of the American Ceramic Society, vol. 103, no. 10, pp. 5442-5453.
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AbstractThe prospect of modifying the surface properties of the substrate (or base) material to enhance its corrosion and wear resistance as well as its reliability, performance, and more importantly its bioactivity is made possible using nanocoatings. An effective technique of synthesizing high purity nanocoatings in addition to nanopowders and fibers is to utilize the sol‐gel approach. It is an attractive and versatile method that can be carried out with relative ease. Ceramic coatings, such as hydroxyapatite (HAp), can be fabricated through chemical means from solutions and consequently complex shapes can be coated economically. Given the fact that mixing takes place on the atomic scale, one of the key advantages of the sol‐gel technique is its capacity to produce homogeneous materials, and it has been shown that the mechanical properties of sol‐gel coatings are enhanced due to the presence of nanocrystalline grain structures. This review covers a brief insight into the recent application of HAp nanocoatings derived from sol‐gel technique.
Colloca, L, Akintola, T, Haycock, NR, Blasini, M, Thomas, S, Phillips, J, Corsi, N, Schenk, LA & Wang, Y 2020, 'Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants', Psychotherapy and Psychosomatics, vol. 89, no. 6, pp. 371-378.
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<b><i>Introduction:</i></b> Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients’ expectations may affect the capacity to respond to placebos in chronic disorders. <b><i>Objective:</i></b> The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. <b><i>Methods:</i></b> We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. <b><i>Results:</i></b> In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. <b><i>Conclusions:</i></b> These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clin...
Coutts, AJ 2020, 'Building a Bridge Between Research and Practice—The Importance of the Practical Application', International Journal of Sports Physiology and Performance, vol. 15, no. 4, pp. 449-449.
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Coyne, JOC, Coutts, AJ, Fomin, R, French, DN, Newton, RU & Haff, GG 2020, 'Heart Rate Variability and Direct Current Measurement Characteristics in Professional Mixed Martial Arts Athletes', Sports, vol. 8, no. 8, pp. 109-109.
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This study’s purpose was to examine heart rate variability (HRV) and direct current potential (DC) measures’ sensitivity and correlations between changes in the acute recovery and stress scale (ARSS) and the previous day’s training load. Training load, HRV, DC and ARSS data were collected from fourteen professional mixed martial arts athletes (32.6 ± 5.3 years, 174.8 ± 8.8 cm, 79.2 ± 17.5 kg) the following morning after hard, easy and rest days. Sensitivity was expressed as a signal-to-noise ratio (SNR, inter-day typical error (TE) or coefficient of variation (%CV) divided by intra-day TE or %CV). Correlations between HRV, DC and ARSS with training load were also examined. The SNRs for the various HRV and DC measures were acceptable to good (1.02–2.85). There was a 23.1% CV average increase between measures taken between different locations versus the same location. Training load changes were not correlated with HRV/DC but were correlated with ARSS stress variables. Practitioners should be aware of HRV/DC variability; however the daily training signal was greater than the test-retest error in this investigation. Upon awakening, HRV/DC measures appear superior for standardization and planning. HRV and DC measures were less sensitive to the previous day’s training load than ARSS measures.
Crabtree, J, Hudson, JL & Newton-John, T 2020, 'Anxiety and Adverse Life Events in Professional Creative and Early Psychosis Populations', Psychiatry, vol. 83, no. 4, pp. 328-343.
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Objective: The association between creativity and psychopathology has intrigued researchers and recent studies have affirmed genetic and epidemiological links. In particular, epidemiological research highlights the need to study what aspects of the creative individual protect or provide risk for transition to psychosis. Two factors, associated with transition to psychosis, will be investigated, namely anxiety and adverse life events. Method: A diverse sample of 110 participants (18-35 years) was examined, including early psychosis (EP), creative professionals who are clinically vulnerable or 'at-risk' (ARCC), those with no psychotic symptoms (CC), and non-creative (NCC) participants. Measures of anxiety (DASS) and adverse life events (ALE) were administered to the participants to determine whether these factors were positively or negatively associated with creativity and whether they were able to differentiate the EP from ARCC, CC and NCC participants. Results: Creative cognition and achievement were positively correlated with anxiety. The EP and ARCC groups were more closely aligned than expected on measures of anxiety and adverse life events. Childhood sexual/physical assault were the only variables that differentiated these two groups. Conclusions: These results provide further support for the association between creative professionals and those with early psychosis. It provides corroborating evidence of the vulnerability of creative individuals who appear to be aligned with the early psychosis group on anxiety, aspects of paranoia and overall trauma. The results provide possible innovative avenues for intervention in EP and ARCC.
Crowcroft, S, Slattery, K, McCleave, E & Coutts, AJ 2020, 'Do Athlete Monitoring Tools Improve a Coach’s Understanding of Performance Change?', International Journal of Sports Physiology and Performance, vol. 15, no. 6, pp. 847-852.
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Purpose: To assess a coach’s subjective assessment of their athletes’ performances and whether the use of athlete-monitoring tools could improve on the coach’s prediction to identify performance changes. Methods: Eight highly trained swimmers (7 male and 1 female, age 21.6 [2.0] y) recorded perceived fatigue, total quality recovery, and heart-rate variability over a 9-month period. Prior to each race of the swimmers’ main 2 events, the coach (n = 1) was presented with their previous race results and asked to predict their race time. All race results (n = 93) with aligning coach’s predictions were recorded and classified as a dichotomous outcome (0 = no change; 1 = performance decrement or improvement [change +/− > or < smallest meaningful change]). A generalized estimating equation was used to assess the coach’s accuracy and the contribution of monitoring variables to the model fit. The probability from generalized estimating equation models was assessed with receiver operating characteristic curves to identify the model’s accuracy from the area under the curve analysis. Results: The coach’s predictions had the highest diagnostic accuracy to identify both decrements (area under the curve: 0.93; 95% confidence interval, 0.88–0.99) and improvements (area under the curve: 0.89; 95% confidence interval, 0.83–0.96) in performance. Conclusions: These findings highlight the high accuracy of a coach’s subjective assessment of performance. Furthermore, the findings provide a future benchmark for athlete-monitoring systems to be able to improve on a coach’s existing understanding of swimming performance.
Cui, L, Wu, J, Pi, D, Zhang, P & Kennedy, P 2020, 'Dual Implicit Mining-Based Latent Friend Recommendation', IEEE Transactions on Systems, Man, and Cybernetics: Systems, vol. 50, no. 5, pp. 1663-1678.
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IEEE The latent friend recommendation in online social media is interesting, yet challenging, because the user-item ratings and the user-user relationships are both sparse. In this paper, we propose a new dual implicit mining-based latent friend recommendation model that simultaneously considers the implicit interest topics of users and the implicit link relationships between the users in the local topic cliques. Specifically, we first propose an algorithm called all reviews from a user and all tags from their corresponding items to learn the implicit interest topics of the users and their corresponding topic weights, then compute the user interest topic similarity using a symmetric Jensen-Shannon divergence. After that, we adopt the proposed weighted local random walk with restart algorithm to analyze the implicit link relationships between the users in the local topic cliques and calculate the weighted link relationship similarity between the users. Combining the user interest topic similarity with the weighted link relationship similarity in a unified way, we get the final latent friend recommendation list. The experiments on real-world datasets demonstrate that the proposed method outperforms the state-of-the-art latent friend recommendation methods under four different types of evaluation metrics.
Curiskis, SA, Drake, B, Osborn, TR & Kennedy, PJ 2020, 'An evaluation of document clustering and topic modelling in two online social networks: Twitter and Reddit', Information Processing & Management, vol. 57, no. 2, pp. 102034-102034.
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© 2019 Elsevier Ltd Methods for document clustering and topic modelling in online social networks (OSNs) offer a means of categorising, annotating and making sense of large volumes of user generated content. Many techniques have been developed over the years, ranging from text mining and clustering methods to latent topic models and neural embedding approaches. However, many of these methods deliver poor results when applied to OSN data as such text is notoriously short and noisy, and often results are not comparable across studies. In this study we evaluate several techniques for document clustering and topic modelling on three datasets from Twitter and Reddit. We benchmark four different feature representations derived from term-frequency inverse-document-frequency (tf-idf) matrices and word embedding models combined with four clustering methods, and we include a Latent Dirichlet Allocation topic model for comparison. Several different evaluation measures are used in the literature, so we provide a discussion and recommendation for the most appropriate extrinsic measures for this task. We also demonstrate the performance of the methods over data sets with different document lengths. Our results show that clustering techniques applied to neural embedding feature representations delivered the best performance over all data sets using appropriate extrinsic evaluation measures. We also demonstrate a method for interpreting the clusters with a top-words based approach using tf-idf weights combined with embedding distance measures.
Currow, DC, Agar, MR & Phillips, JL 2020, 'Role of Hospice Care at the End of Life for People With Cancer', Journal of Clinical Oncology, vol. 38, no. 9, pp. 937-943.
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Patient-defined factors that are important at the end of life include being physically independent for as long as possible, good symptom control, and spending quality time with friends and family. Hospice care adds to the quality of care and these patient-centered priorities for people with cancer and their families in the last weeks and days of life. Evidence from large observational studies demonstrate that hospice care can improve outcomes directly and support better and more appropriate health care use for people in the last stages of cancer. Team-based community hospice care has measurable benefits for patients, their family caregivers, and health services. In addition to improved symptom control for patients and a greater likelihood of time spent at home, caregiver outcomes are better when hospice care is accessed: informational needs are better met, and caregivers have an improved ability to move on with life after the patient’s death compared with people who did not have access to these services. Hospice care continues to evolve as its reach expands and the needs of patients continue to broaden. This is reflected in the transition from hospice being based on excellence in nursing to teams with a broad range of health professionals to meet the complex and changing needs of patients and their families. Additional integration of cancer services with hospice care will help to provide more seamless care for patients and supporting family caregivers during their caregiving and after the death of the patient.
Dalla, PV, Santos, J, Milthorpe, BK & Padula, MP 2020, 'Selectively-Packaged Proteins in Breast Cancer Extracellular Vesicles Involved in Metastasis', International Journal of Molecular Sciences, vol. 21, no. 14, pp. 4990-4990.
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Cancer-derived extracellular vesicles are known to play a role in the progression of the disease. In this rapidly-growing field, there are many reports of phenotypic changes in cells following exposure to cancer-derived extracellular vesicles. This study examines the protein contents of vesicles derived from three well-known breast cancer cell lines, MCF-7, MDA-MB-231 and T47D, using peptide-centric LC-MS/MS and cytokine multiplex immunoassay analysis to understand the molecular basis of these changes. Through these techniques a large number of proteins within these vesicles were identified. A large proportion of these proteins are known to be important in cancer formation and progression and associated with cancer signaling, angiogenesis, metastasis and invasion and immune regulation. This highlights the importance of extracellular vesicles (EVs) in cancer communications and shows some of the mechanisms the vesicles use to assist in cancer progression.
Darcy, S, McKercher, B & Schweinsberg, S 2020, 'From tourism and disability to accessible tourism: a perspective article', Tourism Review, vol. 75, no. 1, pp. 140-144.
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PurposeThis paper aims to examine the development of disability and tourism to the conceptualising and defining of accessible tourism.Design/methodology/approachThis paper uses a limited review of the literature as its main approach.FindingsIn reviewing the development of the field from disability and tourism to accessible tourism, it became apparent that there has been a change in focus on the accessibility of the key sectors of tourism (e.g. transport, accommodation and attractions) to incorporating an embodied understanding of tourism in developing accessible destination experiences that provide an equality of offering to that of nondisabled tourists.Originality/valueThis paper makes a contribution by clearly following the development of the field from papers that only considered tourism and disability to conceptualise and define the accessible tourism field. It then goes on to identify a significant challenge due to an underlying empirical data gap through a lack of nationally and regionally collected tourism data that incorporates disability questions.
Darcy, S, Ollerton, J & Faulkner, S 2020, '“Why Can’t I Play?”: Transdisciplinary Learnings for Children with Disability’s Sport Participation', Social Inclusion, vol. 8, no. 3, pp. 209-223.
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This article explores the constraints to mainstream sports participation of children with disability in community sports clubs and schools through their lived experiences and the perceptions of parents, teachers, coaches, and club officials. It does so by administering an open-ended survey instrument to a sample of participants recruited from schools, sporting facilities, and disability organizations in New South Wales and Victoria, Australia. The data were analysed through a transdisciplinary conceptual framework which brought together the social model of disability (disability studies) with the leisure constraints framework (leisure studies), which have been encouraged by both academics and practitioners. The findings identified ableist and disablist practices, creating an enabled understanding of the facilitators for social inclusion. Participants perceived that interrelated intrapersonal, interpersonal, and structural constraints excluded children from their desired sporting activities. Through applying the social model of disability to the leisure constraints framework, the findings and discussion showed that a great deal of what had been considered intrapersonal constraints of the child with disability could be reinterpreted as interpersonal and structural constraints through enabling socially inclusive practices. The implications are that a social model of disability brings a new social lens to understanding constraints to sport participation for children with disability and can produce effective strategies for inclusion in sport at schools and community sport clubs.
Deplazes, E, Hartmann, LM, Cranfield, CG & Garcia, A 2020, 'Structural Characterization of a Cation-Selective, Self-Assembled Peptide Pore in Planar Phospholipid Bilayers', The Journal of Physical Chemistry Letters, vol. 11, no. 19, pp. 8152-8156.
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GALA is a 30-residue amphipathic peptide that self-assembles into multimeric transmembrane pores in a pH-dependent fashion. In this study, we characterize the size, multimeric structure, and cation selectivity of GALA pores in planar phospholipid bilayers using electrical impedance spectroscopy and molecular dynamics simulations. We demonstrate that in planar bilayers GALA pores are likely formed by six peptide monomers rather than eight to 12 monomers as previously reported for lipid vesicles. We further show that in planar bilayers, GALA pores exhibit previously unreported cation selectivity. We propose that the difference between the predicted pore structures in planar bilayers and lipid vesicles exemplifies the importance of phospholipid bilayer structural properties on the aggregation of transmembrane helical structures.
Deplazes, E, Tafalla, BD, Cranfield, CG & Garcia, A 2020, 'Role of Ion–Phospholipid Interactions in Zwitterionic Phospholipid Bilayer Ion Permeation', The Journal of Physical Chemistry Letters, vol. 11, no. 15, pp. 6353-6358.
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Despite the central role of Na+ and K+ in physiological processes, it is still unclear whether they interact or alter the physical properties of simple zwitterionic phospholipid bilayers at physiologically relevant concentrations. Here we report a difference in membrane permeability between Na+ and K+, as measured with electrical impedance spectroscopy and tethered bilayer lipid membranes. We reveal that the differences in membrane permeability originate from distinct ion coordination by carbonyl oxygens at the phospholipid-water interface, altering the propensity for bilayer pore formation. Molecular dynamics simulations showed differences in the coordination of Na+ and K+ at the phospholipid-water interface of zwitterionic phospholipid bilayers. The ability of Na+ to conscript more phospholipids with a greater number of coordinating interactions causes a higher localized energy barrier for pore formation. These results provide evidence that ion-specific interactions at the phospholipid-water interface can modulate the physical properties of zwitterionic phospholipid bilayers.
Dickson, TJ, Darcy, S & Pentifallo Gadd, C 2020, 'Ensuring volunteer impacts, legacy and leveraging is not “fake news”', International Journal of Contemporary Hospitality Management, vol. 32, no. 2, pp. 683-705.
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PurposeThis study aims to explore the legacy potential of the FIFA Women’s World Cup (FWWC) 2015, for the host communities across Canada.Design/methodology/approachThe mixed-methods study included a link to an online anonymous survey being sent to all volunteers at the FWWC that explored their prior volunteering experience, motivations for volunteering, perceived skill development and future volunteering intentions. Documents were reviewed, and key stakeholders were interviewed.FindingsThe results support previous research that mega-sport event (MSE) volunteers are typically older females with prior volunteering experience. Those most likely to indicate they wanted to volunteer more are younger volunteers without prior volunteering experience. While legacy was discussed as a desired outcome, this was not operationalised through strategic human resource strategies such as being imbedded in the position descriptions for the volunteer managers.Research limitations/implicationsAs this study was conducted in the real-world context of a sport event, the timing of the survey was determined by the organising committee.Practical implicationsMega sport events typically draw upon existing host-city social and human capital. For future event organising committees planning for and delivering a volunteer legacy may require better strategic planning and leveraging relationships with existing host-city volunteer networks. In the context of a single sport, women’s MSE, multi-venue, multi-pro...
Dickson, TJ, Darcy, S & Walker, C 2020, 'A Case of Leveraging a Mega-Sport Event for a Sport Participation and Sport Tourism Legacy: A Prospective Longitudinal Case Study of Whistler Adaptive Sports', Sustainability, vol. 13, no. 1, pp. 170-170.
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Sport participation legacies are often offered as reasons to host mega-sport events, yet there is little evidence to demonstrate the claim’s legitimacy, thus we examine “What did Whistler Sports do to leverage the Vancouver 2010 Olympic and Paralympic Winter Games to facilitate a sport tourism legacy?”. Through a prospective longitudinal case study of WAS and application of the temporal extension of the socioecological framework, multiple data sources were analyzed from over a decade beginning before the event until 2019. The findings reveal the situated and embedded nature of mega-sport event legacies i.e., context. These depend upon a network of facilitators such as local, provincial, and federal policies; pre-event and post-event vision and strategies from local communities and sport organizations; the development of a pool of willing and flexible volunteers. Together these were strategically leveraged to overcome sport participation and sport tourism barriers for people with disabilities. The sport, tourism, and sport tourism experience reflected Whistler’s natural and infrastructure advantage and the needs and desires of locals and visitors with access needs that could not have occurred without the capital injection of the Vancouver 2010 Olympic and Paralympic Games. Leveraging the mega-sport event opportunities required leadership and a strategic vision for repositioning to a year-round program. This strategic change also opened new sport and sport tourism opportunities for current participants but importantly brought new participants and their friendship groups to Whistler over the post-event decade for year-round sustainable adaptive sport opportunities.
DiGiacomo, M, Chang, S, Luckett, T, Agar, M, Phillips, J & Lam, L 2020, 'Financial stress experienced by informal carers of adults with a chronic disease: Results from an Australian population‐based cross‐sectional survey', Australasian Journal on Ageing, vol. 39, no. 3, pp. 254-262.
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AbstractObjectiveTo identify caregiving characteristics that are associated with financial stress in Australian carers of people with a chronic disease.MethodsData were collected via the South Australian Health Omnibus, an annual population‐based, cross‐sectional survey. Individuals who provided care to someone with prevalent chronic conditions were asked about financial stress and caregiving characteristics.ResultsOf 32.4% (988/3047) who were carers, 13.4% (132/988) experienced financial stress. Adjusting for age and household income, providing more than 20 hours of care per week (AOR = 2.39, 95% CI = 1.48‐3.86), transport assistance (AOR = 1.89, 95% CI = 1.15‐3.09) and assistance with household tasks (AOR = 1.92, 95% CI = 1.14‐3.26) and caring for a person with a mental illness (AOR = 2.01, 95% CI = 1.24‐3.28) were associated with a significant increase in odds of experiencing financial stress. Caring for a person with cancer (AOR = 0.49, 95% CI = 0.30‐0.81) or dementia (AOR = 0.40, 95% CI = 0.21‐0.76) was associated with decrease in odds.ConclusionsFinancial stress was reported by more than 13% of carers, and factors other than household income were implicated.
Domínguez Vila, T, Alén González, E & Darcy, S 2020, 'Accessibility of tourism websites: the level of countries’ commitment', Universal Access in the Information Society, vol. 19, no. 2, pp. 331-346.
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© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Various initiatives have been undertaken in recent years to improve the accessibility of tourism in a large number of countries. One of the areas in which work has been done has been the inclusion and accessibility of information for all, especially for people with disabilities and other users with access needs. A focus of this work has been to the digital world, given the increasing relevance of the internet in daily life. This paper aims to determine whether the different nation states are applying appropriate standards, both under their own regulations and under those from United Nations agreements regarding accessibility to online tourism information to foster more sustainable tourism. In the study of official tourism organization website home pages of the countries contained in the World Tourism Organization reports, cluster analysis was used to identify common behaviour patterns. The main result was the need to improve the compatibility and ease of navigation of websites, as well as identifying Japan, Hong Kong and South Korea as countries that can serve as examples of good practice.
Dong, X, Liu, L, Musial, K & Gabrys, B 2020, 'NATS-Bench: Benchmarking NAS Algorithms for Architecture Topology and Size', IEEE transactions on pattern analysis and machine intelligence, vol. PP, pp. 1-1.
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Neural architecture search (NAS) has attracted a lot of attention and hasbeen illustrated to bring tangible benefits in a large number of applicationsin the past few years. Architecture topology and architecture size have beenregarded as two of the most important aspects for the performance of deeplearning models and the community has spawned lots of searching algorithms forboth aspects of the neural architectures. However, the performance gain fromthese searching algorithms is achieved under different search spaces andtraining setups. This makes the overall performance of the algorithms to someextent incomparable and the improvement from a sub-module of the searchingmodel unclear. In this paper, we propose NATS-Bench, a unified benchmark onsearching for both topology and size, for (almost) any up-to-date NASalgorithm. NATS-Bench includes the search space of 15,625 neural cellcandidates for architecture topology and 32,768 for architecture size on threedatasets. We analyze the validity of our benchmark in terms of various criteriaand performance comparison of all candidates in the search space. We also showthe versatility of NATS-Bench by benchmarking 13 recent state-of-the-art NASalgorithms on it. All logs and diagnostic information trained using the samesetup for each candidate are provided. This facilitates a much larger communityof researchers to focus on developing better NAS algorithms in a morecomparable and computationally cost friendly environment. All codes arepublicly available at: https://xuanyidong.com/assets/projects/NATS-Bench.
Donkor, A, Luckett, T, Aranda, S, Vanderpuye, V & Phillips, J 2020, 'Developing a readiness self-assessment tool for low- and middle-income countries establishing new radiotherapy services: A participant validation study', Physica Medica, vol. 71, pp. 88-99.
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PURPOSE:Assessing low-and middle-income countries' (LMICs') readiness to establish new radiotherapy services is an important but empirically understudied concept. The purpose of this study is to develop and confirm a core set of readiness requirements and criteria that can be used to gauge LMICs preparedness to establish radiotherapy services. METHODS:Based on a systematic review and semi-structured expert interviews, a pool of requirements and criteria were generated. To confirm or disconfirm these items, we adopted a synthesised member checking process, also known as participant validation. A purposive sampling strategy was used to recruit radiotherapy experts. Items were sent via email. Each item was reviewed by participants. Qualitative comments were analysed thematically. FINDINGS:Seven of the 17 experts who participated in an earlier semi-structured interview contributed to this participant validation study. The final version of the readiness self-assessment tool for LMICs establishing new radiotherapy services contains 37 requirements mapped into four readiness domains, grouped under the following categories: commitment; cooperation; capacity; and catalyst. Among 23 criteria for commitment domain, participants reviewed 22 as relevant for inclusion. The cooperation requirements considered important, included: "strategic planning team", "stakeholder involvement" and a "technical assistance plan". Capacity requirements, which were endorsed included: "responsible project manager"; "availability of radiotherapy expertise"; and "training for initial core staff". Participants' feedbacks supported the inclusion of all the requirements and criteria related to catalyst. CONCLUSION:The readiness self-assessment tool is a promising planning and evaluation tool for use by stakeholders interested in expanding access to radiotherapy services in LMICs.
Donkor, A, Luckett, T, Aranda, S, Vanderpuye, V & Phillips, J 2020, 'Experiences of barriers and facilitators to establishing and sustaining radiotherapy services in low‐ and middle‐income countries: A qualitative study', Asia-Pacific Journal of Clinical Oncology, vol. 16, no. 2, pp. e74-e85.
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AbstractAimsThe factors contributing to the establishment of high‐quality radiotherapy services in low‐ and middle‐income countries (LMICs) are poorly understood. The aim was to identify and describe barriers and facilitators to establishing and sustaining high‐quality and accessible radiotherapy services in LMICs based on the experience of successful and unsuccessful attempts.MethodsAn exploratory‐descriptive qualitative study using semistructured telephone interviews was undertaken. Purposive and snowball sampling techniques were used to recruit participants. The World Health Organization Innovative Care for Chronic Conditions Framework informed the interview guide. A constant comparative data analysis approach was adopted.FindingsSeventeen participants were interviewed. Ten were working permanently in nine LMICs and seven were permanently employed in four high‐income countries. Three themes were developed: committing to a vision of improving cancer care; making it happen and sustaining a safe service; and leveraging off radiotherapy to strengthen integrated cancer care. Identified barriers included lack of political leadership continuity, lack of a coordinated advocacy effort, non‐Member State of the IAEA, lack of reliable epidemiological data, lack of a comprehensive budget and lack of local expertise. Facilitators identified included strong political support, vision champion, availability of a regulator, costed cancer control plan, diversified sources of funding, responsible project manager, adoption of evidence‐based practice, strategic partnerships, motivation to provide patient‐centered care, and availability of supportive technology.ConclusionsAssessing the level of readiness to establish and...
Donnelly, TJ, Palermo, TM & Newton-John, TRO 2020, 'Parent cognitive, behavioural, and affective factors and their relation to child pain and functioning in pediatric chronic pain: a systematic review and meta-analysis', Pain, vol. 161, no. 7, pp. 1401-1419.
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Abstract Previous studies have demonstrated that parental cognitive, behavioral, and emotional factors are related to child functioning in children and adolescents with chronic pain. This is particularly important to understand how to potentially enhance the efficacy of psychological interventions for children by incorporating interventions targeting parents. We conducted a systematic review and meta-analysis to identify the specific parent factors that have been examined in the literature and to quantify the associations observed between parent factors and child pain and disability. A search of the electronic databases EMBASE, PsychINFO, Medline, and PubMed was conducted, using search terms related to chronic pain, pediatric population, and parents. Fifty-four studies met criteria and were included in the review. Parent pain catastrophizing and protective behavior were the most commonly assessed parental constructs in the literature. Meta-analyses were conducted for associations between parent pain catastrophizing, parent protective behaviors, parent anxiety and depression, and parent stress associated with parenting a child with chronic pain with child pain, disability, school functioning, and emotional functioning. Correlation coefficients were pooled using the random-effects model. A medium relationship was observed between higher protective behavior and poorer school functioning (r = −0.39), and small relationships were found between higher parent pain catastrophizing and increased child disability (r = 0.29); higher protective behaviors and increased child disability (r = 0.25); and increased parent depression and anxiety with increased child disability (r = 0.23 and r = 0.24, respectively). Future research i...
Ejeian, F, Razmjou, A, Nasr-Esfahani, MH, Mohammad, M, Karamali, F, Ebrahimi Warkiani, M, Asadnia, M & Chen, V 2020, '<p>ZIF-8 Modified Polypropylene Membrane: A Biomimetic Cell Culture Platform with a View to the Improvement of Guided Bone Regeneration</p>', International Journal of Nanomedicine, vol. Volume 15, pp. 10029-10043.
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Purpose
Despite the significant advances in modeling of biomechanical aspects of cell microenvironment, it remains a major challenge to precisely mimic the physiological condition of the particular cell niche. Here, the metal-organic frameworks (MOFs) have been introduced as a feasible platform for multifactorial control of cell-substrate interaction, given the wide range of physical and mechanical properties of MOF materials and their structural flexibility.
Results
In situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the polydopamine (PDA)-modified membrane significantly raised surface energy, wettability, roughness, and stiffness of the substrate. This modulation led to an almost twofold increment in the primary attachment of dental pulp stem cells (DPSCs) compare to conventional plastic culture dishes. The findings indicate that polypropylene (PP) membrane modified by PDA/ZIF-8 coating effectively supports the growth and proliferation of DPSCs at a substantial rate. Further analysis also displayed the exaggerated multilineage differentiation of DPSCs with amplified level of autocrine cell fate determination signals, like
BSP1, BMP2, PPARG, FABP4, ACAN, and
COL2A. Notably, osteogenic markers were dramatically overexpressed (more than 100-folds rather than tissue culture plate) in response to biomechanical characteristics of the ZIF-8 layer.
Conclusion
Hence, surface modification of cell culture platforms with MOF nanostructures proposed as a powerful nanomedical approach for selectively guiding stem cells for tissue regeneration. In particular, PP/PDA/ZIF-8 membrane presented ideal characteristics for using as a barrier membrane for guided bone regeneration (GBR) in periodontal tissue engineering.
Fachal, L, Aschard, H, Beesley, J, Barnes, DR, Allen, J, Kar, S, Pooley, KA, Dennis, J, Michailidou, K, Turman, C, Soucy, P, Lemaçon, A, Lush, M, Tyrer, JP, Ghoussaini, M, Moradi Marjaneh, M, Jiang, X, Agata, S, Aittomäki, K, Alonso, MR, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arason, A, Arndt, V, Aronson, KJ, Arun, BK, Auber, B, Auer, PL, Azzollini, J, Balmaña, J, Barkardottir, RB, Barrowdale, D, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Białkowska, K, Blanco, AM, Blomqvist, C, Blot, W, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Borg, A, Bosse, K, Brauch, H, Brenner, H, Briceno, I, Brock, IW, Brooks-Wilson, A, Brüning, T, Burwinkel, B, Buys, SS, Cai, Q, Caldés, T, Caligo, MA, Camp, NJ, Campbell, I, Canzian, F, Carroll, JS, Carter, BD, Castelao, JE, Chiquette, J, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Collée, JM, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Cybulski, C, Czene, K, Daly, MB, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dite, GS, Domchek, SM, Dörk, T, dos-Santos-Silva, I, Droit, A, Dubois, S, Dumont, M, Duran, M, Durcan, L, Dwek, M, Eccles, DM, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Fletcher, O, Floris, G, Flyger, H, Foretova, L, Foulkes, WD, Friedman, E, Fritschi, L, Frost, D, Gabrielson, M, Gago-Dominguez, M, Gambino, G, Ganz, PA, Gapstur, SM, Garber, J, García-Sáenz, JA, Gaudet, MM, Georgoulias, V, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Tibiletti, MG, Greene, MH, Grip, M, Gronwald, J, Grundy, A, Guénel, P, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Harrington, PA, Hartikainen, JM, Hartman, M, He, W, Healey, CS, Heemskerk-Gerritsen, BAM, Heyworth, J, Hillemanns, P, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Hopper, JL, Howell, A, Huang, G, Hulick, PJ, Imyanitov, EN, Isaacs, C, Iwasaki, M, Jager, A, Jakimovska, M, Jakubowska, A, James, PA, Janavicius, R, Jankowitz, RC, John, EM, Johnson, N, Jones, ME, Jukkola-Vuorinen, A, Jung, A, Kaaks, R, Kang, D, Kapoor, PM, Karlan, BY, Keeman, R, Kerin, MJ, Khusnutdinova, E, Kiiski, JI, Kirk, J, Kitahara, CM, Ko, Y-D, Konstantopoulou, I, Kosma, V-M, Koutros, S, Kubelka-Sabit, K, Kwong, A, Kyriacou, K, Laitman, Y, Lambrechts, D, Lee, E, Leslie, G, Lester, J, Lesueur, F, Lindblom, A, Lo, W-Y, Long, J, Lophatananon, A, Loud, JT, Lubiński, J, MacInnis, RJ, Maishman, T, Makalic, E & et al. 2020, 'Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes', Nature Genetics, vol. 52, no. 1, pp. 56-73.
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© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.
Fajardo, J, Milthorpe, BK & Santos, J 2020, 'Molecular Mechanisms Involved in Neural Substructure Development during Phosphodiesterase Inhibitor Treatment of Mesenchymal Stem Cells', International Journal of Molecular Sciences, vol. 21, no. 14, pp. 4867-4867.
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Stem cells are highly important in biology due to their unique innate ability to self-renew and differentiate into other specialised cells. In a neurological context, treating major injuries such as traumatic brain injury, spinal cord injury and stroke is a strong basis for research in this area. Mesenchymal stem cells (MSC) are a strong candidate because of their accessibility, compatibility if autologous, high yield and multipotency with a potential to generate neural cells. With the use of small-molecule chemicals, the neural induction of stem cells may occur within minutes or hours. Isobutylmethyl xanthine (IBMX) has been widely used in cocktails to induce neural differentiation. However, the key molecular mechanisms it instigates in the process are largely unknown. In this study we showed that IBMX-treated mesenchymal stem cells induced differentiation within 24 h with the unique expression of several key proteins such as Adapter protein crk, hypoxanthine-guanine phosphoribosyltransferase, DNA topoisomerase 2-beta and Cell division protein kinase 5 (CDK5), vital in linking signalling pathways. Furthermore, the increased expression of basic fibroblast growth factor in treated cells promotes phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) cascades and GTPase–Hras interactions. Bioinformatic and pathway analyses revealed upregulation in expression and an increase in the number of proteins with biological ontologies related to neural development and substructure formation. These findings enhance the understanding of the utility of IBMX in MSC neural differentiation and its involvement in neurite substructure development.
Fanchini, M, Steendahl, IB, Impellizzeri, FM, Pruna, R, Dupont, G, Coutts, AJ, Meyer, T & McCall, A 2020, 'Exercise-Based Strategies to Prevent Muscle Injury in Elite Footballers: A Systematic Review and Best Evidence Synthesis', Sports Medicine, vol. 50, no. 9, pp. 1653-1666.
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Farrar, MA, Carey, KA, Paguinto, S-G, Kasparian, NA & De Abreu Lourenço, R 2020, '“The Whole Game is Changing and You’ve Got Hope”: Australian Perspectives on Treatment Decision Making in Spinal Muscular Atrophy', The Patient - Patient-Centered Outcomes Research, vol. 13, no. 4, pp. 389-400.
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INTRODUCTION:The natural history and treatment of spinal muscular atrophy (SMA) is currently being transformed by the development and availability of novel therapies, with significant related changes in practice. This not only has important implications for the health and wellbeing of patients with SMA and their families, as well as improves the quality of care. OBJECTIVE:The present study aimed to investigate the processes and factors that influence treatment and healthcare decisions for children and adults with SMA and their families and healthcare providers. METHODS:Four focus groups comprising adults, or parents of children and adolescents, with SMA and an expert panel of healthcare providers (N = 25) explored experiences of SMA, its treatment and related decision making and expectations for future care. Group discussions were recorded and transcribed verbatim for thematic analysis using NVivo12.0. RESULTS:People with SMA, their families and healthcare providers described confronting complex healthcare decisions in the context of a rapidly changing SMA treatment environment. Across all groups, five key themes were identified: hope, yearning and searching, patient-centred care and support, community and a sense of connectedness and weighing up potential treatment benefits and costs. Essential to these themes was the notion of what it means to live with SMA and complexities relating to 'quality of life'. CONCLUSION:Identifying and more deeply understanding the factors that influence patient, family and healthcare providers' decision making regarding SMA treatment is an important first step in improving the quality of patient- and family-centred care and in informing clinical practice and future health policy incorporating personalized medicine and optimal supportive and mental health care.
Fathollahipour, S, Koosha, M, Tavakoli, J, Maziarfar, S & Fallah Mehrabadi, J 2020, 'Erythromycin Releasing PVA/sucrose and PVA/honey Hydrogels as Wound Dressings with Antibacterial Activity and Enhanced Bio-adhesion.', Iran J Pharm Res, vol. 19, no. 1, pp. 448-464.
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The present study deals with preparation and characterization of thermally crosslinked PVA-based hydrogels containing honey and sucrose for the purpose of erythromycin delivery. The hydrogels have been characterized and compared by scanning electron microscopy, Fourier transform infrared spectroscopy, and bio-adhesion tests. Swelling measurements showed that addition of sucrose and honey decreased the equilibrium swelling of the hydrogels. Results of release studies showed that the amount of erythromycin, released at the early hours was higher for PVA/sucrose and PVA/honey hydrogels compared to PVA hydrogel while the drug released at later times was highly reduced for PVA/honey hydrogel. Both Peppas-Sahlin and Korsmeyer-Peppas models fitted well to the release data. Fitting Peppas-Sahlin model to the release data showed that at the initial times, release of drug from the hydrogel network was mainly governed by Fickian mechanism; however, at later times the drug is dominantly released by relaxational mechanism due to swelling of the network,. Addition of honey improved the bio-adhesion of PVA/honey hydrogel as compared to PVA/sucrose and pure PVA hydrogel. Results of antibacterial tests showed growth inhibitory action of erythromycin-loaded PVA hydrogels against Pseudomonas aeruginosa and Staphylococcus aureus bacteria. This study indicates that these hybrid hydrogels are capable of being used as functional wound dressings aiming to control the rate of antibiotic delivery to the wound site and prevent the wounds from infection.
Feng, M, Zhang, X, Wu, WW, Chen, ZH, Oliver, BG, McDonald, VM, Zhang, HP, Xie, M, Qin, L, Zhang, J, Wang, L, Li, WM, Wang, G & Gibson, PG 2020, 'Clinical and Inflammatory Features of Exacerbation-Prone Asthma: A Cross-Sectional Study Using Multidimensional Assessment', Respiration, vol. 99, no. 12, pp. 1109-1121.
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<b><i>Background:</i></b> Reducing asthma exacerbations is a major target of current clinical guidelines, but identifying features of exacerbation-prone asthma (EPA) using multidimensional assessment (MDA) is lacking. <b><i>Objective:</i></b> To systemically explore the clinical and inflammatory features of adults with EPA in a Chinese population. <b><i>Methods:</i></b> We designed a cross-sectional study using the Severe Asthma Web-based Database from the Australasian Severe Asthma Network (ASAN). Eligible Chinese adults with asthma (<i>n</i> = 546) were assessed using MDA. We stratified patients based on exacerbation frequency: none, few (1 or 2), and exacerbation prone (≥3). Univariate and multivariable negative binomial regression analyses were performed to investigate features associated with the frequency of exacerbations. <b><i>Results:</i></b> Of 546 participants, 61.9% had no exacerbations (<i>n</i> = 338), 29.6% had few exacerbations (<i>n</i> = 162), and 8.4% were exacerbation prone (<i>n</i> = 46) within the preceding year. EPA patients were characterized by elevated blood and sputum eosinophils but less atopy, with more controller therapies but worse asthma control and quality of life (all <i>p</i> < 0.05). In multivariable models, blood and sputum eosinophils (adjusted rate ratio = 2.23, 95% confidence interval = [1.26, 3.84] and 1.67 [1.27, 2.21], respectively), FEV<sub>1</sub> (0.90 [0.84, 0.96]), bronchodilator responsiveness (1.16 [1.05, 1.27]), COPD (2.22 [1.41, 3.51]), bronchiectasis (2.87 [1.69, 4.89]), anxiety (2.56 [1.10, 5.95]), and depression (1.94 [1.20, 3.13]) were found. Further, upper respiratory tract infection (1.83 [1.32, 2.54]) and food allergy (1.67 [1.23, 2.25]) were at high risk of asthma symptom triggers. <b><i>Conclusion:&...
Ferreira, B, Maharaj, S, Simpson, A, Nassif, N & Lal, S 2020, 'The metabolic role of depression and burnout in nurses', Translational Metabolic Syndrome Research, vol. 3, pp. 9-11.
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Ferreira, DH, Boland, JW, Kochovska, S, Honson, A, Phillips, JL & Currow, DC 2020, 'Patients’ and caregivers’ experiences of driving with chronic breathlessness before and after regular low-dose sustained-release morphine: A qualitative study', Palliative Medicine, vol. 34, no. 8, pp. 1078-1087.
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Background: Chronic breathlessness is a disabling syndrome that profoundly impacts patients’ and caregivers’ lives. Driving is important for most people, including those with advanced disease. Regular, low-dose, sustained-release morphine safely reduces breathlessness, but little is known about its impact on driving. Aim: To understand patients’ and caregivers’ (1) perspectives and experiences of driving with chronic breathlessness; and (2) perceived impact of regular, low-dose, sustained-release morphine on driving. Design: A qualitative study embedded in a pragmatic, phase III, randomised, placebo-controlled trial of low-dose, sustained-release morphine (⩽32 mg/24 h) for chronic breathlessness. Semi-structured interviews were conducted immediately after participants withdrew or completed the randomised, placebo-controlled trial. Informed by grounded theory, a constant comparative approach to analysis was adopted. Setting/participants: Participants were recruited from an outpatients palliative care service in Adelaide, Australia. Participants included patients ( n = 13) with severe breathlessness associated with chronic obstructive pulmonary disease and their caregivers ( n = 9). Results: Participants were interviewed at home. Eleven received morphine 8–32 mg. Three themes emerged: (1) independence; (2) breathlessness’ impact on driving; and (3) driving while taking regular, low-dose, sustained-release morphine. Conclusion: Driving contributed to a sense of identity and independence. Being able to drive increased the physical and social space available to patients and caregivers, their social engageme...
Ferreira, DH, Kochovska, S, Honson, A, Phillips, JL & Currow, DC 2020, 'Two faces of the same coin: a qualitative study of patients’ and carers’ coexistence with chronic breathlessness associated with chronic obstructive pulmonary disease (COPD)', BMC Palliative Care, vol. 19, no. 1.
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Abstract Background Chronic breathlessness is a recognized clinical syndrome that severely impacts patients and carers, who become increasingly restricted in their daily activities. Often, patients become reliant on their carers, who are required to provide constant support. Although individual experiences of breathlessness have been previously investigated, there are few studies exploring contemporaneous experiences of breathlessness of the patient and their carer. This study aimed to understand the experience of severe chronic breathlessness in people with chronic obstructive pulmonary disease (COPD) from the perspective of the patient and carer unit. Methods A qualitative study embedded in a randomised, placebo-controlled effectiveness study (RCT) of regular, low-dose (≤32 mg/day), sustained-release morphine for chronic breathlessness associated with COPD. Recruitment occurred between July 2017 and November 2018 in one respiratory and palliative care services, in South Australia. Participants were community-dwelling patients with COPD and severe breathlessness (modified Medical Research Council scale 3 or 4) and their carers. Separate semi-structured interviews were conducted with patients and carers, recorded and transcribed verbatim. Analysis was informed by grounded theory using a constant comparative approach. Results From the 26 patients with a carer recruited for the RCT in South Australia, nine were interviewed in their homes. Six patients were men, median age 77 years. Carers were mostly women, who were their wives (n = 6), median age 70. Five themes emerged from the data: (1) shrinking world; (2) mutu...
Findlay, M, Brown, C, De Abreu Lourenço, R, White, K & Bauer, J 2020, 'Sarcopenia and myosteatosis in patients undergoing curative radiotherapy for head and neck cancer: Impact on survival, treatment completion, hospital admission and cost', Journal of Human Nutrition and Dietetics, vol. 33, no. 6, pp. 811-821.
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AbstractBackgroundComputed tomography (CT) is the gold standard of body composition analysis at the tissue‐organ level. The present study aimed to determine the impact of CT‐defined sarcopenia and myosteatosis on outcomes, including overall survival, unplanned hospital admissions and related costs, in patients who had completed treatment of curative intent for head and neck cancer (HNC).MethodsRetrospective observational study of patients undergoing radiotherapy of curative intent ± other treatment modalities for HNC. Tissue density data derived at the third lumbar vertebra (L3) were evaluated with sarcopenia defined per sex‐specific published threshold values for skeletal muscle index, stratified by body mass index and mean skeletal muscle attenuation in HU (Hounsfield units).ResultsPre‐ or post‐treatment images were available for 79/98 patients (80.6%) and 61/98 patients (62.2%), respectively. Sarcopenia was present in 42/79 patients pre‐treatment and 36/61 patients post‐treatment, whereas myosteatosis was present in 63/79 patients pre‐treatment and 48/61 patients post‐treatment. In patients with pre‐ and post‐treatment images (n = 60), the median (range) percentage weight change was −8.5% (−29.9 to +11.7). On multivariable analysis, a post‐treatment sarcopenia hazard ratio of 3.87 (95% confidence interval = 1.22–12.24, P = 0.021) and a pre‐treatment myosteatosis hazard ratio of 8.86 (95% confidence interval = 1.12–69.88, P = 0.038) were independent predictors of reduced overall survival. There was no difference in radiotherapy or chemotherapy treatment completion based on pre‐treatment sarcopenia status. The mean (SD) difference unplanned hospital admission cost was $15 846 ($17 7...
Findlay, M, Rankin, NM, Shaw, T, White, K, Boyer, M, Milross, C, De Abreu Lourenço, R, Brown, C, Collett, G, Beale, P & Bauer, JD 2020, 'Best Evidence to Best Practice: Implementing an Innovative Model of Nutrition Care for Patients with Head and Neck Cancer Improves Outcomes', Nutrients, vol. 12, no. 5, pp. 1465-1465.
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Malnutrition is prevalent in patients with head and neck cancer (HNC), impacting outcomes. Despite publication of nutrition care evidence-based guidelines (EBGs), evidence–practice gaps exist. This study aimed to implement and evaluate the integration of a patient-centred, best-practice dietetic model of care into an HNC multidisciplinary team (MDT) to minimise the detrimental sequelae of malnutrition. A mixed-methods, pre–post study design was used to deliver key interventions underpinned by evidence-based implementation strategies to address identified barriers and facilitators to change at individual, team and system levels. A data audit of medical records established baseline adherence to EBGs and clinical parameters prior to implementation in a prospective cohort. Key interventions included a weekly Supportive Care-Led Pre-Treatment Clinic and a Nutrition Care Dashboard highlighting nutrition outcome data integrated into MDT meetings. Focus groups provided team-level evaluation of the new model of care. Economic analysis determined system-level impact. The baseline clinical audit (n = 98) revealed barriers including reactive nutrition care, lack of familiarity with EBGs or awareness of intensive nutrition care needs as well as infrastructure and dietetic resource limitations. Post-implementation data (n = 34) demonstrated improved process and clinical outcomes: pre-treatment dietitian assessment; use of a validated nutrition assessment tool before, during and after treatment. Patients receiving the new model of care were significantly more likely to complete prescribed radiotherapy and systemic therapy. Differences in mean percentage weight change were clinically relevant. At the system level, the new model of care avoided 3.92 unplanned admissions and related costs of $AUD121K per annum. Focus groups confirmed clear support at the multidisciplinary team level for continuing the new model of care. Implementing an evidence-based nutrition mo...
Frost, SA, Kelly, A, Gaudin, J, Evoy, LM, Wilson, C, Marov, L, El Haddad, C, Center, J, Eisman, JA, Nguyen, TV & Hassett, G 2020, 'Establishing baseline absolute risk of subsequent fracture among adults presenting to hospital with a minimal-trauma-fracture', BMC Musculoskeletal Disorders, vol. 21, no. 1.
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AbstractBackgroundOne in three women and one in five men are expected to experience a minimal-trauma-fracture after the age of 50-years, which increases the risk of subsequent fracture. Importantly, timely diagnosis and optimal treatment in the form of a fracture liaison service (FLS), has been shown to reduce this risk of a subsequent fracture. However, baseline risk of subsequent fracture among this group of FLS patients has not been well described. Therefore, this study aims to estimate absolute risk of subsequent fracture, among women and men aged 50-years or more, presenting to hospital with a minimal-trauma-fracture.MethodsWomen and men aged 50-years or more with a minimal-trauma-fracture, presenting to hospitals across the South Western Sydney Local Health District between January 2003 and December 2017 were followed to identify subsequent fracture presentations to hospital. Absolute risk of subsequent fracture was estimated, by taking into account the competing risk of death.ResultsBetween January 2003 and December 2017–15,088 patients presented to the emergency departments of the five hospitals in the SWSLHD (11,149, women [74%]), with minimal-trauma-fractures. Subsequent fractures identified during the follow-up period (median = 4.5 years [IQR, 1.6–8.2]), occurred in 2024 (13%) patients. Death during the initial hospital stay, or during a subsequent hospital visit was recorded among 1646 patients (11%). Women were observed to have 7.1% risk of subsequent fracture after 1-year, following an initial fracture; and, the risk of subsequent fracture after 1-year was 6.2% for men. After 5-years the rate among women was 13.7, and 11.3% for men, respectively. Cumulative risk of subsequent fracture when initial fractures were classified as being at proxim...
Garcia, A, Deplazes, E, Aili, S, Padula, MP, Touchard, A, Murphy, C, Mirissa Lankage, U, Nicholson, GM, Cornell, B & Cranfield, CG 2020, 'Label-Free, Real-Time Phospholipase-A Isoform Assay', ACS Biomaterials Science & Engineering, vol. 6, no. 8, pp. 4714-4721.
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© 2020 American Chemical Society. Phospholipase-A (PLA) enzymes catalyze the hydrolysis of ester bonds in select glycerophospholipids. Sensors for rapidly measuring the PLA activity in biological samples have relevance in the study of venom compositions and in medical diagnostics for the diagnosis of diseases such as acute pancreatitis. Current PLA sensor technologies are often restricted by the time it takes to prepare an assay, the necessity of using fluorescent labels, or the fact they might require strict pH control of the buffer vehicles used. Here we present a tethered bilayer lipid membrane (tBLM) impedance sensor array for the rapid and real-time detection of PLA, which includes the ability to selectively detect phospholipase-A2 (PLA2) from phospholipase-A1 (PLA1) isoforms. Comparing the activity of PLA1 and PLA2 in an array of tBLMs composed of ether phospholipids, ester phospholipids or ether-ester phospholipids allows for the rapid and reliable distinction between the isoforms, as measured using swept-frequency electrical impedance spectroscopy. After testing the assay using pure enzymes, we demonstrate the capacity of the sensor to identify specific PLA2-type, calcium-dependent activity from the venom of the South American bullet ant, Paraponera clavata, at a concentration of 1 μg/mL. The specificity of the phospholipase activity was corroborated using matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. As further validation, we tested the activities of a PLA1 isoform in the presence of different buffers commonly used in biology and biochemistry experiments. Sensitivity testing shows that PLA1 can be detected at an activity as low as 0.06 U/mL. The rapid and reliable detection of phospholipases presented in this study has potential applications in the study of animal venoms as well as in lipase bioreactors and point-of-care devices.
Geia, L, Baird, K, Bail, K, Barclay, L, Bennett, J, Best, O, Birks, M, Blackley, L, Blackman, R, Bonner, A, Bryant AO, R, Buzzacott, C, Campbell, S, Catling, C, Chamberlain, C, Cox, L, Cross, W, Cruickshank, M, Cummins, A, Dahlen, H, Daly, J, Darbyshire, P, Davidson, P, Denney-Wilson, E, De Souza, R, Doyle, K, Drummond, A, Duff, J, Duffield, C, Dunning, T, East, L, Elliott, D, Elmir, R, Fergie OAM, D, Ferguson, C, Fernandez, R, Flower AM, D, Foureur, M, Fowler, C, Fry, M, Gorman, E, Grant, J, Gray, J, Halcomb, E, Hart, B, Hartz, D, Hazelton, M, Heaton, L, Hickman, L, Homer AO, CSE, Hungerford, C, Hutton, A, Jackson AO, D, Johnson, A, Kelly, MA, Kitson, A, Knight, S, Levett-Jones, T, Lindsay, D, Lovett, R, Luck, L, Molloy, L, Manias, E, Mannix, J, Marriott, AMR, Martin, M, Massey, D, McCloughen, A, McGough, S, McGrath, L, Mills, J, Mitchell, BG, Mohamed, J, Montayre, J, Moroney, T, Moyle, W, Moxham, L, Northam OAM, H, Nowlan, S, O'Brien, AP, Ogunsiji, O, Paterson, C, Pennington, K, Peters, K, Phillips, J, Power, T, Procter, N, Ramjan, L, Ramsay, N, Rasmussen, B, Rihari-Thomas, J, Rind, B, Robinson, M, Roche, M, Sainsbury, K, Salamonson, Y, Sherwood, J, Shields, L, Sim, J, Skinner, I, Smallwood, G, Smallwood, R, Stewart, L, Taylor, S, Usher AM, K, Virdun, C, Wannell, J, Ward, R, West, C, West, R, Wilkes, L, Williams, R, Wilson, R, Wynaden, D & Wynne, R 2020, 'A unified call to action from Australian nursing and midwifery leaders: ensuring that Black lives matter', Contemporary Nurse, vol. 56, no. 4, pp. 297-308.
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Ghorbani, F, Fathi, F, Aghebati-Maleki, L, Abolhasan, R, Rikhtegar, R, Dolatabadi, JEN, Babaloo, Z, Khalilzadeh, B, Ebrahimi-Warkiani, M, Sharifzadeh, Z, Rashidi, M-R & Yousefi, M 2020, 'Kinetic and thermodynamic study of c-Met interaction with single chain fragment variable (scFv) antibodies using phage based surface plasmon resonance', European Journal of Pharmaceutical Sciences, vol. 150, pp. 105362-105362.
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Mesenchymal epithelial transition factor (c-Met) has been recently regarded as an attractive target for the treatment of cancer. Our previous study showed that c-Met-specific single chain fragment variables (scFvs) can be considered as a promising therapy for cancer, however, their molecular interaction with c-Met protein have not been assessed. Accordingly, in the current study we aim to evaluate the kinetic and thermodynamic properties of c-Met interaction with these scFvs as anticancer agents by means of surface plasmon resonance (SPR) technique. Phage-scFvs were immobilized on the 11-mercaptoundecanoic acid gold chips after carboxylic groups activation by N-ethyl-N-(3-diethylaminopropyl) carbodiimide/N-hydroxysuccinimide and, then the c-Met binding to each scFvs (ES1, ES2, and ES3) at different concentrations (ranging from 20 to 665 μM) was explored. Kinetic studies revealed that ES1 has the highest affinity (KD = 3.36 × 10-8) toward its target at 25°C. Calculation of thermodynamic parameters also showed positive values for enthalpy and entropy changes, which was representative of hydrophobic forces between c-Met and ES1. Furthermore, the positive value of Gibbs free energy indicated that c-Met binding to ES1 was enthalpy-driven. Taken together, we concluded that produced ES1 can be applied as promising scFv-based therapy for diagnosis or targeting of c-Met in various cancers.
Grandou, C, Wallace, L, Impellizzeri, FM, Allen, NG & Coutts, AJ 2020, 'Overtraining in Resistance Exercise: An Exploratory Systematic Review and Methodological Appraisal of the Literature', Sports Medicine, vol. 50, no. 4, pp. 815-828.
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BACKGROUND:The balance between training stress and recovery is important for inducing adaptations to improve athletic performance. However, continuously high training loads with insufficient recovery may cause fatigue to accumulate and result in overtraining. A comprehensive systematic review is required to collate overtraining literature and improve the current understanding of the mechanisms underlying functional overreaching (FOR), non-functional overreaching (NFOR) and the overtraining syndrome (OTS) in resistance training. OBJECTIVE:The objective of this systematic review was to establish markers of overtraining and elucidate the mechanisms underlying maladaptive resistance training conditions. Furthermore, this review aims to critically evaluate the methodological approaches of the overtraining literature. METHODS:A systematic literature search was performed on PubMed, Web of Science and SPORTDiscus to identify studies up to June 2019. Electronic databases were searched using terms related to resistance training and overtraining. Records were included if they attempted to induce a state of overreaching or overtraining through resistance exercise in healthy participants. RESULTS:A total of 22 studies were selected for review. Among these studies, eight resulted in decrements in performance and measured changes in performance during a follow-up period. There were four studies that reported decrease in performance yet failed to implement follow-up measures. A total of 10 studies reported no decline in performance. Overall, a lack of standardisation in methodology (follow-up performance testing) and diagnostic criteria prevents consistent determination of FOR, NFOR and OTS in resistance training. CONCLUSIONS:Few studies have appropriately established FOR, NFOR or OTS in resistance training. Overtraining may be related to frequent high-intensity and monotonous resistance training. However, no marker other than a sustained decrease in performance has been establi...
Ha, VKL, Chai, R & Nguyen, HT 2020, 'A Telepresence Wheelchair with 360-Degree Vision Using WebRTC', Applied Sciences, vol. 10, no. 1, pp. 369-369.
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This paper presents an innovative approach to develop an advanced 360-degree vision telepresence wheelchair for healthcare applications. The study aims at improving a wide field of view surrounding the wheelchair to provide safe wheelchair navigation and efficient assistance for wheelchair users. A dual-fisheye camera is mounted in front of the wheelchair to capture images which can be then streamed over the Internet. A web real-time communication (WebRTC) protocol was implemented to provide efficient video and data streaming. An estimation model based on artificial neural networks was developed to evaluate the quality of experience (QoE) of video streaming. Experimental results confirmed that the proposed telepresence wheelchair system was able to stream a 360-degree video surrounding the wheelchair smoothly in real-time. The average streaming rate of the entire 360-degree video was 25.83 frames per second (fps), and the average peak signal to noise ratio (PSNR) was 29.06 dB. Simulation results of the proposed QoE estimation scheme provided a prediction accuracy of 94%. Furthermore, the results showed that the designed system could be controlled remotely via the wireless Internet to follow the desired path with high accuracy. The overall results demonstrate the effectiveness of our proposed approach for the 360-degree vision telepresence wheelchair for assistive technology applications.
Haddadi, N, Travis, G, Nassif, NT, Simpson, AM & Marsh, DJ 2020, 'Toward Systems Pathology for PTEN Diagnostics', Cold Spring Harbor Perspectives in Medicine, vol. 10, no. 5, pp. a037127-a037127.
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Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline PTEN mutation. Furthermore, outside of the familial setting, somatic variants of PTEN occur in numerous malignancies. Here we introduce and discuss the prospect of moving toward a systems pathology approach for PTEN diagnostics, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a PTEN mutation. Detection of a germline PTEN mutation can inform cancer surveillance and in the case of somatic mutation, have value in predicting disease course. Given that PTEN functions in the PI3K/AKT/mTOR pathway, identification of a PTEN mutation may highlight new therapeutic opportunities and/or inform therapeutic choices.
Haeusler, GM, Phillips, R, Slavin, MA, Babl, FE, De Abreu Lourenco, R, Mechinaud, F & Thursky, KA 2020, 'Re-evaluating and recalibrating predictors of bacterial infection in children with cancer and febrile neutropenia', EClinicalMedicine, vol. 23, pp. 100394-100394.
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BackgroundNumerous paediatric febrile neutropenia (FN) clinical decision rules (CDRs) have been derived. Validation studies show reduced performance in external settings. We evaluated the association between variables common across published FN CDRs and bacterial infection and recalibrated existing CDRs using these data.MethodsProspective data from the Australian-PICNICC study which enrolled 858 FN episodes in children with cancer were used. Variables shown to be significant predictors of infection or adverse outcome in >1 CDR were analysed using multivariable logistic regression. Recalibration included re-evaluation of beta-coefficients (logistic model) or recursive-partition analysis (tree-based models).FindingsTwenty-five unique variables were identified across 17 FN CDRs. Fourteen were included in >1 CDR and 10 were analysed in our dataset. On univariate analysis, location, temperature, hypotension, rigors, severely unwell and decreasing platelets, white cell count, neutrophil count and monocyte count were significantly associated with bacterial infection. On multivariable analysis, decreasing platelets, increasing temperature and the appearance of being clinically unwell remained significantly associated. Five rules were recalibrated. Across all rules, recalibration increased the AUC-ROC and low-risk yield as compared to non-recalibrated data. For the SPOG-adverse event CDR, recalibration also increased sensitivity and specificity and external validation showed reproducibility.InterpretationDegree of marrow suppression (low platelets), features of inflammation (temperature) and clinical judgement (severely unwell) have been consistently shown to predict infection in children with FN. Recalibration of existing CDRs is a novel way to improve diagnostic performance of CDRs and maintain relevance over time.
Haeusler, GM, Thursky, KA, Slavin, MA, Babl, FE, De Abreu Lourenco, R, Allaway, Z, Mechinaud, F & Phillips, R 2020, 'Risk stratification in children with cancer and febrile neutropenia: A national, prospective, multicentre validation of nine clinical decision rules', eClinicalMedicine, vol. 18, pp. 100220-100220.
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© 2019 Background: Reduced intensity treatment of low-risk febrile neutropenia (FN) in children with cancer is safe and improves quality of life. Identifying children with low-risk FN using a validated risk stratification strategy is recommended. This study prospectively validated nine FN clinical decision rules (CDRs) designed to predict infection or adverse outcome. Methods: Data were collected on consecutive FN episodes in this multicentre, prospective validation study. The reproducibility and discriminatory ability of each CDR in the validation cohort was compared to the derivation dataset and details of missed outcomes were reported. Findings: There were 858 FN episodes in 462 patients from eight hospitals included. Bacteraemia occurred in 111 (12·9%) and a non-bacteraemia microbiological documented infection in 185 (21·6%). Eight CDRs exhibited reproducibility and sensitivity ranged from 64% to 96%. Rules that had >85% sensitivity in predicting outcomes classified few patients (<20%) as low risk. For three CDRs predicting a composite outcome of any bacterial or viral infection, the sensitivity and discriminatory ability improved for prediction of bacterial infection alone. Across all CDRs designed to be implemented at FN presentation, the sensitivity improved at day 2 assessment. Interpretation: While reproducibility was observed in eight out of the nine CDRs, no rule perfectly differentiated between children with FN at high or low risk of infection. This is in keeping with other validation studies and highlights the need for additional safeguards against missed infections or adverse outcomes before implementation can be considered.
Hagihghi, R, Razmjou, A, Orooji, Y, Warkiani, ME & Asadnia, M 2020, 'A miniaturized piezoresistive flow sensor for real‐time monitoring of intravenous infusion', Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 108, no. 2, pp. 568-576.
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AbstractDrug overdose (DO) is considered one of the current issues of intravenous (IV) infusion particularly resulting in serious injuries and deaths. Malfunction of infusion pumps is reported as the main cause of the drug overdose. Live monitoring and flow rate calculation by health professionals have been practicing to avoid DO. However, human errors and miscalculations are inevitable. A secondary measurement tool is required to avoid the risk of OD when infusion pump malfunctions cannot be detected immediately. Here, inspired by nature, we developed a real‐time monitoring device through which an administrator can review, evaluate, and modify the IV infusion process. Our flow sensor possesses an erected polymer hair cell on a multi‐layered silicon base forming from a patterned gold strained gauge layer on a piezoresistive liquid crystal polymer (LCP) membrane. Gold strain gauges on an LCP membrane have been used instead of a piezoresistive silicon membrane as the sensing element. The combination of gold strain gauges and LCP membrane provides better sensitivity than a piezoresistive silicon membrane of the same dimensions and thickness. We also miniaturized our biocompatible sensor such that it can be possible to install it inside the IV tube in contact with the liquid providing an in‐suite online flow monitoring. The proposed LCP membrane sensor is compared with two commercially available IV sensors to validate its flow sensing ability. The experimental results demonstrate that the proposed sensor provides a low threshold detection limit of 5 mL/hr, which betters the performance of other commercial sensors at low flow rates.
Hassanzadeh-Barforoushi, A, Warkiani, ME, Gallego-Ortega, D, Liu, G & Barber, T 2020, 'Capillary-assisted microfluidic biosensing platform captures single cell secretion dynamics in nanoliter compartments', Biosensors and Bioelectronics, vol. 155, pp. 112113-112113.
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Cancer cells continuously secrete inflammatory biomolecules which play significant roles in disease progression and tumor metastasis toward secondary sites. Despite recent efforts to capture cancer cells' intercellular secretion heterogeneity using microfluidics, the challenges in operation of these systems as well as the complexity of designing a biosensing assay for long-term and real-time measurement of single cell secretions have become grand research barriers. Here, we present a new capillary-based microfluidic biosensing approach to easily and reliably capture ~500 single cells inside isolated dead-end nanoliter compartments using simple pipette injection, and quantify their individual secretion dynamics at the single cell resolution over a long period of culture (~16 h). We first present a detailed investigation of the fluid mechanics underlying the formation of nanoliter compartments in the microfluidic system. Based on the measurement of single cell capture efficiency, we employ a one-step FRET-based biosensor which monitors the single cancer cells' protease activity. The sensor reports the fluorescent signal as a product of amino acid chain cleavage and reduction in its quenching capability. Using the single cell protease secretion data, we identified modes of cell secretion dynamics in our cell sample. While most of the cells had low secretion levels, two other smaller and more aggressive secretion dynamics were cells with secretion modes that include sharp spikes or slow but progressive trend. The method presented here overcomes the difficulties associated with performing single cell secretion assays, enabling a feasible and reliable technique for high throughput measurement of metabolic activities in cancer cells.
Hayati, H, Eager, D, Peham, C & Qi, Y 2020, 'Dynamic Behaviour of High Performance of Sand Surfaces Used in the Sports Industry', Vibration, vol. 3, no. 4, pp. 410-424.
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The sand surface is considered a critical injury and performance contributing factor in different sports, from beach volleyball to greyhound racing. However, there is still a significant gap in understanding the dynamic behaviour of sport sand surfaces, particularly their vibration behaviour under impact loads. The purpose of this research was to introduce different measurement techniques to the study of sports sand surface dynamic behaviour. This study utilised an experimental drop test, accelerometry, in-situ moisture content and firmness data, to investigate the possible correlation between the sand surface and injuries. The analysis is underpinned by data gathered from greyhound racing and discussed where relevant.
Hayati, H, Eager, D, Pendrill, A-M & Alberg, H 2020, 'Jerk within the Context of Science and Engineering—A Systematic Review', Vibration, vol. 3, no. 4, pp. 371-409.
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Rapid changes in forces and the resulting changes in acceleration, jerk and higher order derivatives can have undesired consequences beyond the effect of the forces themselves. Jerk can cause injuries in humans and racing animals and induce fatigue cracks in metals and other materials, which may ultimately lead to structure failures. This is a reason that it is used within standards for limits states. Examples of standards which use jerk include amusement rides and lifts. Despite its use in standards and many science and engineering applications, jerk is rarely discussed in university science and engineering textbooks and it remains a relatively unfamiliar concept even in engineering. This paper presents a literature review of the jerk and higher derivatives of displacement, from terminology and historical background to standards, measurements and current applications.
He, P, Gelissen, IC & Ammit, AJ 2020, 'Regulation of ATP binding cassette transporter A1 (ABCA1) expression: cholesterol-dependent and – independent signaling pathways with relevance to inflammatory lung disease', Respiratory Research, vol. 21, no. 1.
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AbstractThe role of the ATP binding cassette transporter A1 (ABCA1) in maintaining cellular lipid homeostasis in cardiovascular disease is well established. More recently, the important beneficial role played by ABCA1 in modulating pathogenic disease mechanisms, such as inflammation, in a broad range of chronic conditions has been realised. These studies position ABCA1 as a potential therapeutic target in a diverse range of diseases where inflammation is an underlying cause. Chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) are driven by inflammation, and as such, there is now a growing recognition that we need a greater understanding of the signaling pathways responsible for regulation of ABCA1 expression in this clinical context. While the signaling pathways responsible for cholesterol-mediated ABCA1 expression have been clearly delineated through decades of studies in the atherosclerosis field, and thus far appear to be translatable to the respiratory field, less is known about the cholesterol-independent signaling pathways that can modulate ABCA1 expression in inflammatory lung disease. This review will identify the various signaling pathways and ligands that are associated with the regulation of ABCA1 expression and may be exploited in future as therapeutic targets in the setting of chronic inflammatory lung diseases.
Henderson, MJ, Chrismas, BCR, Stevens, CJ, Coutts, AJ & Taylor, L 2020, 'Changes in Core Temperature During an Elite Female Rugby Sevens Tournament', International Journal of Sports Physiology and Performance, vol. 15, no. 4, pp. 571-580.
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Purpose: To characterize player core temperature (Tc) across a World Rugby Women’s Sevens Series tournament day (WRWSS) and determine the efficacy of commonly employed cold-water-immersion (CWI) protocols. Methods: Tc was measured in 12 elite female rugby sevens athletes across 3 games (G1–3) from day 1 of the Sydney WRWSS tournament. Symptoms of exertional heat illness, perceptual scales, CWI details, playing minutes, external-load data (measured by global positioning systems), and wet-bulb globe temperature (range 18.5°C–20.1°C) were also collected. Linear mixed models and magnitude-based inferences were used to assess differences in Tc between periods (G1–3 and warm-ups [WU]). Results: Average Tc was “very likely” lower (effect size; ±90% confidence limit −0.33; ±0.18) in G1 than in G2. Peak Tc was “very likely” (0.71; ±0.28) associated with increased playing time. CWI did not remove the accumulated Tc due to WU and match-play activity (∼1°C–2°C rise in Tc still present compared with Tc at WU onset for players ≥6-min match play). Conclusions: Elite WRWSS athletes experienced high Tc during WU (Tc peak 37.9–39.0°C) and matches (Tc peak 37.9–39.8°C), a magnitude known to reduce intermittent high-intensity physical performance (≥39°C). The CWI protocol resulted in players (≥6-min match play) with ∼1°C to 2°C raised Tc compared with Tc at WU onset.
Heneka, N, Bhattarai, P, Shaw, T, Rowett, D, Lapkin, S & Phillips, JL 2020, 'Mitigating opioid errors in inpatient palliative care: A qualitative study', Collegian, vol. 27, no. 3, pp. 304-312.
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© 2019 Australian College of Nursing Ltd Background: Opioids are high-risk medicines used in high doses and volumes in specialist palliative care inpatient services to manage palliative patients’ pain and other symptoms. Despite the high volume of opioid use in this care setting, serious errors with opioids are exceedingly rare. However, little is known about the factors that mitigate opioid errors in specialist palliative care inpatient services. Aim: To explore palliative care clinicians’ perceptions of factors that mitigate opioid errors in specialist palliative care inpatient services. Methods and design: A qualitative study using focus groups and semi-structured interviews. Participants and setting: Registered nurses, doctors, and/or pharmacists (‘clinicians’) who were involved with and/or had oversight of the services’ opioid delivery and/or opioid quality and safety processes, employed by one of three specialist palliative care inpatient services in metropolitan NSW. Findings: Fifty-eight participants took part in this study, three-quarters (76%) of whom were palliative care nurses. A positive opioid safety culture was central to mitigating opioid errors in specialist palliative care inpatient services. This culture of opioid safety was founded on clear and consistent safety messages from leadership, clinicians empowered to work together and practise safely, and a non-punitive approach to errors when they occurred. The clinical nurse educator was seen as pivotal to shaping, driving and reinforcing safe opioid delivery practices across the palliative care service. Conclusion: Creating and sustaining a positive opioid safety culture, and promoting non-punitive approaches to opioid error and reporting, is essential to mitigating opioid errors in the specialist palliative care inpatient setting.
Herath, S, Razavi Bazaz, S, Monkman, J, Ebrahimi Warkiani, M, Richard, D, O’Byrne, K & Kulasinghe, A 2020, 'Circulating tumor cell clusters: Insights into tumour dissemination and metastasis', Expert Review of Molecular Diagnostics, vol. 20, no. 11, pp. 1139-1147.
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INTRODUCTION:Metastasis results in more than 90% of cancer related deaths globally. The process is thought to be facilitated by metastatic precursor cells, commonly termed circulating tumour cells (CTCs). CTCs can exist as single cells or cell clusters and travel through the lymphovasculature to distant organs where they can form overt metastasis. Areas covered: Studies have highlighted that CTC clusters, which may be homotypic or heterotypic in composition, have a higher metastatic potential compared to single CTCs. The characterisation of CTC clusters is becoming important as heterotypic clusters can provide a mechanism for immune evasion. This review summarises the latest advances in CTC cluster mediated metastasis and clinical significance. Expert Opinion: Comprehensive characterisation of CTC clusters is needed to understand the cell types and interactions within clusters, in order to identify ways in which to reduce CTC cluster mediated metastasis. The role of CTC clusters in prognosticating disease progression needs to be determined by documenting CTC clusters from the time of diagnosis over the course of therapy.
Hesam-Shariati, N, Chang, W-J, McAuley, JH, Booth, A, Trost, Z, Lin, C-T, Newton-John, T & Gustin, SM 2020, 'The Analgesic Effect of Electroencephalographic Neurofeedback for People With Chronic Pain: Protocol for a Systematic Review and Meta-analysis', JMIR Research Protocols, vol. 9, no. 10, pp. e22821-e22821.
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Background Chronic pain is a global health problem, affecting around 1 in 5 individuals in the general population. The understanding of the key role of functional brain alterations in the generation of chronic pain has led researchers to focus on pain treatments that target brain activity. Electroencephalographic neurofeedback attempts to modulate the power of maladaptive electroencephalography frequency powers to decrease chronic pain. Although several studies have provided promising evidence, the effect of electroencephalographic neurofeedback on chronic pain is uncertain. Objective This systematic review aims to synthesize the evidence from randomized controlled trials to evaluate the analgesic effect of electroencephalographic neurofeedback. In addition, we will synthesize the findings of nonrandomized studies in a narrative review. Methods We will apply the search strategy in 5 electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, and CINAHL) for published studies and in clinical trial registries for completed unpublished studies. We will include studies that used electroencephalographic neurofeedback as an intervention for people with chronic pain. Risk-of-bias tools will be used to assess methodological quality of the included studies. We will include randomized controlled trials if they have compared electroencephalographic neurofeedback with any other intervention or placebo control. The data from randomized controlled trials will be aggregated to perform a meta-analysis for quantitative synthesis. The primary outcome measure is pain intensity assessed by self-report scales. Secondary outcome measures include depressive s...
Hesam-Shariati, N, Chang, W-J, McAuley, JH, Booth, A, Trost, Z, Lin, C-T, Newton-John, T & Gustin, SM 2020, 'The Analgesic Effect of Electroencephalographic Neurofeedback for People With Chronic Pain: Protocol for a Systematic Review and Meta-analysis (Preprint)'.
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BACKGROUND Chronic pain is a global health problem, affecting around 1 in 5 individuals in the general population. The understanding of the key role of functional brain alterations in the generation of chronic pain has led researchers to focus on pain treatments that target brain activity. Electroencephalographic neurofeedback attempts to modulate the power of maladaptive electroencephalography frequency powers to decrease chronic pain. Although several studies have provided promising evidence, the effect of electroencephalographic neurofeedback on chronic pain is uncertain.
OBJECTIVE This systematic review aims to synthesize the evidence from randomized controlled trials to evaluate the analgesic effect of electroencephalographic neurofeedback. In addition, we will synthesize the findings of nonrandomized studies in a narrative review.
METHODS We will apply the search strategy in 5 electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, and CINAHL) for published studies and in clinical trial registries for completed unpublished studies. We will include studies that used electroencephalographic neurofeedback as an intervention for people with chronic pain. Risk-of-bias tools will be used to assess methodological quality of the included studies. We will include randomized controlled trials if they have compared electroencephalographic neurofeedback with any other intervention or placebo control. The data from randomized controlled trials will be aggregated to perform a meta-analysis for quantitative synthesis. The primary outcome measure is pain intensity assessed by self-report scales. Secondary o...
Hesam-Shariati, N, Newton-John, T, Singh, AK, Tirado Cortes, CA, Do, T-TN, Craig, A, Middleton, JW, Jensen, MP, Trost, Z, Lin, C-T & Gustin, SM 2020, 'Evaluation of the Effectiveness of a Novel Brain-Computer Interface Neuromodulative Intervention to Relieve Neuropathic Pain Following Spinal Cord Injury: Protocol for a Single-Case Experimental Design With Multiple Baselines', JMIR Research Protocols, vol. 9, no. 9, pp. e20979-e20979.
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Background Neuropathic pain is a debilitating secondary condition for many individuals with spinal cord injury. Spinal cord injury neuropathic pain often is poorly responsive to existing pharmacological and nonpharmacological treatments. A growing body of evidence supports the potential for brain-computer interface systems to reduce spinal cord injury neuropathic pain via electroencephalographic neurofeedback. However, further studies are needed to provide more definitive evidence regarding the effectiveness of this intervention. Objective The primary objective of this study is to evaluate the effectiveness of a multiday course of a brain-computer interface neuromodulative intervention in a gaming environment to provide pain relief for individuals with neuropathic pain following spinal cord injury. Methods We have developed a novel brain-computer interface-based neuromodulative intervention for spinal cord injury neuropathic pain. Our brain-computer interface neuromodulative treatment includes an interactive gaming interface, and a neuromodulation protocol targeted to suppress theta (4-8 Hz) and high beta (20-30 Hz) frequency powers, and enhance alpha (9-12 Hz) power. We will use a single-case experimental design with multiple baselines to examine the effectiveness of our self-developed brain-computer interface neuromodulative intervention for the treatment of spinal cord injury neuropathic pain. We will recruit 3 participants with spinal cord injury neuropathic pain. Each participant will be randomly allocated to a different baseline phase (ie, 7, 10, or 14 days), which will then be followed by 20 sessions of a 30-minute brain-computer interface neuromodulative interventi...
Hickman, L, Ferguson, C, Davidson, PM, Allida, S, Inglis, S, Parker, D & Agar, M 2020, 'Key elements of interventions for heart failure patients with mild cognitive impairment or dementia: A systematic review', European Journal of Cardiovascular Nursing, vol. 19, no. 1, pp. 8-19.
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Background: The purpose of this systematic review was to (a) examine the effects of interventions delivered by a heart failure professional for mild cognitive impairment and dementia on cognitive function, memory, working memory, instrumental activities of daily living, heart failure knowledge, self-care, quality of life and depression; and (b) identify the successful elements of these strategies for heart failure patients with mild cognitive impairment or dementia. Methods and results: During March 2018, an electronic search of databases including CINAHL, MEDLINE, EMBASE and PsycINFO was conducted. All randomised controlled trials, which examined an intervention strategy to help heart failure patients with mild cognitive impairment or dementia cope with self-care, were included. An initial search yielded 1622 citations, six studies were included ( N= 595 participants, mean age 68 years). There were no significant improvements in cognitive function and depression. However, significant improvements were seen in memory ( p=0.015), working memory ( p=0.029) and instrumental activities of daily living ( p=0.006). Nurse led interventions improved the patient’s heart failure knowledge ( p=0.001), self-care ( p<0.05) and quality of life ( p=0.029). Key elements of these interventions include brain exercises, for example, syllable stacks, individualised assessment and customised education, personalised self-care schedule development, interactive problem-solving training on scenarios and association techniques to prompt self-care activities. Conclusions: Modest evidence for nurse led interventions among heart failure patients with mild cognitive impairment or dementia was identified. These results must be interpreted with caution in light of the limited number of available included studies.
Ho-Le, TP & Nguyen, TV 2020, 'Hip Fracture and Mortality: A Loss of Life Expectancy Interpretation', Journal of Bone and Mineral Research, vol. 36, no. 12, pp. 2457-2458.
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Ho-Pham, LT, Doan, MC, Van, LH & Nguyen, TV 2020, 'Development of a model for identification of individuals with high risk of osteoporosis', Archives of Osteoporosis, vol. 15, no. 1, p. 111.
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Many developing countries, including Vietnam, lack DXA resources for the diagnosis of osteoporosis, which poses difficulties in the treatment and prevention of osteoporosis at the individual level. We have developed and validated a prediction model for individualized assessment of osteoporosis based on age and body weight for men and women. PURPOSE:To estimate the prevalence of osteoporosis and to develop and validate a prediction model for estimating the absolute risk of osteoporosis in the Vietnamese population. METHODS:The study involved 1477 women and 669 men aged 50 years and older, who were recruited from the general population in Ho Chi Minh City (Vietnam). Bone mineral density (BMD) at the femoral neck, total hip, and lumbar spine was measured by DXA (Hologic Horizon). The diagnosis of osteoporosis was based on BMD T-score (T-score ≤ - 2.5) at the femoral neck or lumbar spine which was derived from a published reference range for the Vietnamese population. The logistic regression model was used to develop the prediction model for men and women separately. The bootstrap method was used to evaluate the model performance using 3 indices: the area under the receiver's operating characteristic curve (AUC), Brier score, and R-squared values. RESULTS:The prevalence of osteoporosis at any site was 28.3% in women and 15.5% in men. The best predictors of osteoporosis risk were age and body weight. Using these indices, a cut-off of 0.195 for women yielded an AUC of 0.825, Brier score = 0.112, and it explained 33.8% of total variance in risk of osteoporosis between individuals. Similarly, in men, the internal validation with a cut-off of 0.09 yielded good accuracy, with AUC = 0.858, Brier score = 0.040, and R-squared = 30.3%. CONCLUSION:We have developed and validated a prediction model for individualized assessment of osteoporosis. In settings without DXA, this model can serve as a useful screening tool to identify high-risk individuals for DXA scan.
Hosie, A, Phillips, J, Lam, L, Kochovska, S, Noble, B, Brassil, M, Kurrle, S, Cumming, A, Caplan, GA, Chye, R, Ely, EW, Lawlor, PG, Bush, SH, Davis, JM, Lovell, M, Parr, C, Williams, S, Hauser, K, McArdle, S, Jacquier, K, Phillipson, C, Kuwahata, L, Kerfoot, J, Brown, L, Fazekas, B, Cheah, SL, Edwards, L, Green, A, Hunt, J, Attwood, R, Assen, T, Garcia, M, Wilcock, J & Agar, M 2020, 'A Multicomponent Nonpharmacological Intervention to Prevent Delirium for Hospitalized People with Advanced Cancer: A Phase II Cluster Randomized Waitlist Controlled Trial (The PRESERVE Pilot Study)', Journal of Palliative Medicine, vol. 23, no. 10, pp. 1314-1322.
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Background: Delirium is a common debilitating complication of advanced cancer. Objective: To determine if a multicomponent nonpharmacological delirium prevention intervention was feasible for adult patients with advanced cancer, before a phase III (efficacy) trial. Design: Phase II (feasibility) cluster randomized controlled trial. All sites implemented delirium screening and diagnostic assessment. Strategies within sleep, vision and hearing, hydration, orientation, mobility, and family domains were delivered to enrolled patients at intervention site admission days 1-7. Control sites then implemented the intervention ('waitlist sites'). Setting: Four Australian palliative care units. Measurements: The primary outcome was adherence, with an a priori endpoint of at least 60% patients achieving full adherence. Secondary outcomes were interdisciplinary care delivery, delirium measures, and adverse events, analyzed descriptively and inferentially. Results: Sixty-five enrolled patients (25 control, 20 intervention, and 20 waitlist) had 98% delirium screens and 75% diagnostic assessments completed. Nurses (67%), physicians (16%), allied health (8.4%), family (7%), patients (1%), and volunteers (0.5%) delivered the intervention. There was full adherence for 5% patients at intervention sites, partial for 25%. Both full and partial adherence were higher at waitlist sites: 25% and 45%, respectively. One-third of control site patients (32%) became delirious within seven days of admission compared to one-fifth (20%) at both intervention and waitlist sites (p = 0.5). Mean (standard deviation) Delirium Rating Scale-Revised-1998 scores were 16.8 + 12.0 control sites versus 18.4 + 8.2 (p = 0.6) intervention and 18.7 + 7.8 (p = 0.5) waitlist sites. The intervention caused no adverse events. Conclusion: The intervention requires modification for optimal adherence in a phase III trial.
Hossain, MI, Eager, D & Walker, PD 2020, 'Greyhound racing ideal trajectory path generation for straight to bend based on jerk rate minimization', Scientific Reports, vol. 10, no. 1, p. 7088.
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AbstractThis paper presents methods for modelling and designing an ideal path trajectory between straight and bend track path segments for racing greyhounds. To do this, we numerically generate clothoid and algebraic curve segments for racing quadrupeds using a sequential vector transformation method as well as using a helper equation for approaching ideal clothoid segments that would respect greyhound kinematic parameters and boundary conditions of the track. Further, we look into the limitations of using a clothoid curve for racing dog track path design and propose a smooth composite curve for track transition design which roughly maintains G3 curvature continuity for smooth jerk to overcome limitations of a clothoid transition. Finally, we show results from race data modelling and past injury data, which provide a strong indication of clothoid curve segments improving the dynamics and safety of racing greyhounds while reducing injuries.
Huang, Y, Song, R, Argha, A, Savkin, AV, Celler, BG & Su, SW 2020, 'Continuous Description of Human 3D Motion Intent Through Switching Mechanism', IEEE Transactions on Neural Systems and Rehabilitation Engineering, vol. 28, no. 1, pp. 277-286.
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© 2001-2011 IEEE. Post-stroke motor recovery highly relies on voluntarily participating in active rehabilitation as early as possible for promoting the reorganization of the patient's brain. In this paper, a new method is proposed which manipulates cable-based rehabilitation robots to assist multi-joint body motions. This uses an electromyography (EMG) decoder for continuous estimation of voluntary motion intention to establish a cooperative human-machine interface for promoting the participation in rehabilitation exercises. In particular, for multi-joint complex tasks in three-dimensional space, a switching mechanism has been developed which can carve up tasks into separate simple motions. For each simple motion, a linear six-inputs and three-outputs time-invariant model is established respectively. The inputs are the processed muscle activations of six arm muscles, and the outputs are voluntary forces of participants when executing a multi-directional tracking task with visual feedback. The experiments for examining the decoder model and EMG-based controller include model training, testing and controller application phases with seven healthy participants. Experimental results demonstrate that the decoder model with the switching mechanism could effectively recognize arm movement intention and provide appropriate assistance to the participants. This study finds that the switching mechanism can improve both the model estimation accuracy and the completeness for executing complex tasks.
Huang, Z, Wong, L-W, Su, Y, Huang, X, Wang, N, Chen, H & Yi, C 2020, 'Blood-brain barrier integrity in the pathogenesis of Alzheimer’s disease', Frontiers in Neuroendocrinology, vol. 59, pp. 100857-100857.
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The blood-brain barrier (BBB) tightly controls the molecular exchange between the brain parenchyma and blood. Accumulated evidence from transgenic animal Alzheimer's disease (AD) models and human AD patients have demonstrated that BBB dysfunction is a major player in AD pathology. In this review, we discuss the role of the BBB in maintaining brain integrity and how this is mediated by crosstalk between BBB-associated cells within the neurovascular unit (NVU). We then discuss the role of the NVU, in particular its endothelial cell, pericyte, and glial cell constituents, in AD pathogenesis. The effect of substances released by the neuroendocrine system in modulating BBB function and AD pathogenesis is also discussed. We perform a systematic review of currently available AD treatments specifically targeting pericytes and BBB glial cells. In summary, this review provides a comprehensive overview of BBB dysfunction in AD and a new perspective on the development of therapeutics for AD.
Impellizzeri, FM, Franchi, MV, Sarto, F, Meyer, T & Coutts, AJ 2020, 'Sharing information is probably more helpful than providing generic training recommendations on return to play after COVID-19 home confinement', Science and Medicine in Football, vol. 4, no. 3, pp. 169-170.
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Impellizzeri, FM, McCall, A, Ward, P, Bornn, L & Coutts, AJ 2020, 'Training Load and Its Role in Injury Prevention, Part 2: Conceptual and Methodologic Pitfalls', Journal of Athletic Training, vol. 55, no. 9, pp. 893-901.
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In part 2 of this clinical commentary, we highlight the conceptual and methodologic pitfalls evident in current training-load–injury research. These limitations make these studies unsuitable for determining how to use new metrics such as acute workload, chronic workload, and their ratio for reducing injury risk. The main overarching concerns are the lack of a conceptual framework and reference models that do not allow for appropriate interpretation of the results to define a causal structure. The lack of any conceptual framework also gives investigators too many degrees of freedom, which can dramatically increase the risk of false discoveries and confirmation bias by forcing the interpretation of results toward common beliefs and accepted training principles. Specifically, we underline methodologic concerns relating to (1) measure of exposures, (2) pitfalls of using ratios, (3) training-load measures, (4) time windows, (5) discretization and reference category, (6) injury definitions, (7) unclear analyses, (8) sample size and generalizability, (9) missing data, and (10) standards and quality of reporting. Given the pitfalls of previous studies, we need to return to our practices before this research influx began, when practitioners relied on traditional training principles (eg, overload progression) and adjusted training loads based on athletes' responses. Training-load measures cannot tell us whether the variations are increasing or decreasing the injury risk; we recommend that practitioners still rely on their expert knowledge and experience.
Impellizzeri, FM, Menaspà, P, Coutts, AJ, Kalkhoven, J & Menaspà, MJ 2020, 'Training Load and Its Role in Injury Prevention, Part I: Back to the Future', Journal of Athletic Training, vol. 55, no. 9, pp. 885-892.
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The purpose of this 2-part commentary series is† to explain why we believe our ability to control injury risk by manipulating training load (TL) in its current state is an illusion and why the foundations of this illusion are weak and unreliable. In part 1, we introduce the training process framework and contextualize the role of TL monitoring in the injury-prevention paradigm. In part 2, we describe the conceptual and methodologic pitfalls of previous authors who associated TL and injury in ways that limited their suitability for the derivation of practical recommendations. The first important step in the training process is developing the training program: the practitioner develops a strategy based on available evidence, professional knowledge, and experience. For decades, exercise strategies have been based on the fundamental training principles of overload and progression. Training-load monitoring allows the practitioner to determine whether athletes have completed training as planned and how they have coped with the physical stress. Training load and its associated metrics cannot provide a quantitative indication of whether particular load progressions will increase or decrease the injury risk, given the nature of previous studies (descriptive and at best predictive) and their methodologic weaknesses. The overreliance on TL has moved the attention away from the multifactorial nature of injury and the roles of other important contextual factors. We argue that no evidence supports the quantitative use of TL data to manipulate future training with the purpose of preventing injury. Therefore, determining “how much is too much” and how to properly manipulate and progress TL are currently subjective decisions based on generic training principles and our experience of adjusting training according to an individual athlete's response. Our message to practitioners is to stop seeking overly simplistic solutions to complex problems and instead embrace ...
Impellizzeri, FM, Tenan, MS, Kempton, T, Novak, A & Coutts, AJ 2020, 'Acute:Chronic Workload Ratio: Conceptual Issues and Fundamental Pitfalls', International Journal of Sports Physiology and Performance, vol. 15, no. 6, pp. 907-913.
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The number of studies examining associations between training load and injury has increased exponentially. As a result, many new measures of exposure and training-load-based prognostic factors have been created. The acute:chronic workload ratio (ACWR) is the most popular. However, when recommending the manipulation of a prognostic factor in order to alter the likelihood of an event, one assumes a causal effect. This introduces a series of additional conceptual and methodological considerations that are problematic and should be considered. Because no studies have even tried to estimate causal effects properly, manipulating ACWR in practical settings in order to change injury rates remains a conjecture and an overinterpretation of the available data. Furthermore, there are known issues with the use of ratio data and unrecognized assumptions that negatively affect the ACWR metric for use as a causal prognostic factor. ACWR use in practical settings can lead to inappropriate recommendations, because its causal relation to injury has not been established, it is an inaccurate metric (failing to normalize the numerator by the denominator even when uncoupled), it has a lack of background rationale to support its causal role, it is an ambiguous metric, and it is not consistently and unidirectionally related to injury risk. Conclusion: There is no evidence supporting the use of ACWR in training-load-management systems or for training recommendations aimed at reducing injury risk. The statistical properties of the ratio make the ACWR an inaccurate metric and complicate its interpretation for practical applications. In addition, it adds noise and creates statistical artifacts.
Impellizzeri, FM, Ward, P, Coutts, AJ, Bornn, L & McCall, A 2020, 'Training Load and Injury Part 1: The Devil Is in the Detail—Challenges to Applying the Current Research in the Training Load and Injury Field', Journal of Orthopaedic & Sports Physical Therapy, vol. 50, no. 10, pp. 574-576.
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Background
This article sets the scene for a critique of the research underpinning 2 common clinical assumptions: (1) training workload is a key factor influencing sports injury risk, and (2) training workload can be manipulated to reduce injury risk. In this clinical commentary, we address why it is important for clinicians to critically evaluate the evidence behind research conclusions.Clinical question
Has research been designed and conducted well enough to help clinicians answer the questions, 'What is the relationship between training workload and sports injury risk?' and 'Can the metrics based on training workload be used to decrease injury risk?'Key results
In the past decade, many sports injury researchers have developed new measures of exposure, based on internal and external training workload, to study the relationship between training load and injury. Some of these metrics may have been embraced by researchers and clinicians because (1) they are apparently supported by the scientific literature, (2) they are simple to calculate and use (averages and their ratio), and (3) there is an apparent reasonable rationale/narrative to support using workload metrics. However, intentional or unintentional questionable research practices and overinterpretation of research results undermine the trustworthiness of research in the training load and sports injury field.Clinical application
Clinicians should always aim to critically examine the credibility of the evidence behind a research conclusion before implementing research findings in practice. Something that initially looks promising and inviting might not be as revolutionary or useful as one first anticipated. J Orthop Sports Phys Ther 2020;50(10):574-576. Epub 1 Aug 2020. doi:10.2519/jospt.2020.9675.
Impellizzeri, FM, Ward, P, Coutts, AJ, Bornn, L & McCall, A 2020, 'Training Load and Injury Part 2: Questionable Research Practices Hijack the Truth and Mislead Well-Intentioned Clinicians', Journal of Orthopaedic & Sports Physical Therapy, vol. 50, no. 10, pp. 577-584.
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Background
In this clinical commentary, we highlight issues related to conceptual foundations and methods used in training load and injury research. We focus on sources of degrees of freedom that can favor questionable research practices such as P hacking and hypothesizing after the results are known, which can undermine the trustworthiness of research findings.Clinical question
Is the methodological rigor of studies in the training load and injury field sufficient to inform training-related decisions in clinical practice?Key results
The absence of a clear conceptual framework, causal structure, and reliable methods can promote questionable research practices, selective reporting, and confirmation bias. The fact that well-accepted training principles (eg, overload progression) are in line with some study findings may simply be a consequence of confirmation bias, resulting from cherry picking and emphasizing results that align with popular beliefs. Identifying evidence-based practical applications, grounded in high-quality research, is not currently possible. The strongest recommendation we can make for the clinician is grounded in common sense: 'Do not train too much, too soon'-not because it has been confirmed by studies, but because it reflects accepted generic training principles.Clinical application
The training load and injury research field has fundamental conceptual and methodological weaknesses. Therefore, making decisions about planning and modifying training programs for injury reduction in clinical practice, based on available studies, is premature. Clinicians should continue to rely on best practice, experience, and well-known training principles, and consider the potential influence of contextual factors when planning and monitoring training loads. J Orthop Sports Phys Ther 2020;50(10):577-584. Epub 1 Aug 2020. doi:10.2519/jospt.2020.9211.
Jeffries, AC, Wallace, L, Coutts, AJ, Cohen, AM, McCall, A & Impellizzeri, FM 2020, 'Injury, Illness, and Training Load in a Professional Contemporary Dance Company: A Prospective Study', Journal of Athletic Training, vol. 55, no. 9, pp. 967-976.
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ContextProfessional dance is a demanding physical activity with high injury rates. Currently, no epidemiologic data exist regarding the incidence of injury and illness together with training load (TL) over a long period of time.ObjectiveTo provide a detailed description of injury, illness, and TL occurring in professional contemporary dancers.DesignDescriptive epidemiology study.SettingA single professional contemporary dance company during a 1-year period.Patients or Other ParticipantsA total of 16 male and female professional contemporary dancers.Main Outcome Measure(s)Injury data consisted of medical-attention injury (Med-Inj) and time-loss injury (Time-Inj). Illness was measured using the Wisconsin Upper Respiratory Tract Infection Survey. Training load was collected for each dance session using the session rating of perceived exertion and classified into 3 groups based on individual and group percentiles: low, medium, or high.ResultsReported injuries totaled 79 (86.1% new, 6.3% reinjury, and 7.6% exacerbation). The Med-Inj incidence rate was 4.6 per 1000 hours (95% confidence interval [CI] = 3.8, 5.8), and the Time-Inj rate was 1.4 per 1000 hours (95% CI = 0.8, 2.1). The median time until injury for Med-Inj and Time-Inj was 3 months. The number of days dancers experienced illness symptoms was 39.9 ± 26.9 (range = 1–96), with an incidence rate of 9.1 per 1000 hours (95% CI = 7.7, 10.7). Mean weekly TL was 6685 ± 1605 (4641–10 391; arbitrary units). Inconsistent results were found for the incidence of injury and illness based on individu...
Jeffries, AC, Wallace, L, Coutts, AJ, McLaren, SJ, McCall, A & Impellizzeri, FM 2020, 'Athlete-Reported Outcome Measures for Monitoring Training Responses: A Systematic Review of Risk of Bias and Measurement Property Quality According to the COSMIN Guidelines', International Journal of Sports Physiology and Performance, vol. 15, no. 9, pp. 1203-1215.
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Background: Athlete-reported outcome measures (AROMs) are frequently used in research and practice but no studies have examined their psychometric properties. Objectives: Part 1—identify the most commonly used AROMs in sport for monitoring training responses; part 2—assess risk of bias, measurement properties, and level of evidence, based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. Study Appraisal and Synthesis Methods: Methodological quality of the studies, quality of measurement properties, and level of evidence were determined using the COSMIN checklist and criteria. Results: Part 1—from 9446 articles screened for title and abstract, 310 out of 334 full texts were included; 53.9% of the AROMs contained multiple items, while 46.1% contained single items. Part 2—from 1895 articles screened for title and abstract, 71 were selected. Most measurement properties of multiple-item AROMs were adequate, but content validity and measurement error were inadequate. With the exclusion of 2 studies examining reliability and responsiveness, no validity studies were found for single items. Conclusions: The measurement properties of multiple-item AROMs derived from psychometrics were acceptable (with the exclusion of content validity and measurement error). The single-item AROMs most frequently used in sport science have not been validated. Additionally, nonvalidated modified versions of the originally nonvalidated items are common. Until proper validation studies are completed, all conclusions based on these AROMs are questionable. Established reference methods, such as those of clinimetrics, should be used to develop and assess the validity of AROMs.
Johansen, MD, Irving, A, Montagutelli, X, Tate, MD, Rudloff, I, Nold, MF, Hansbro, NG, Kim, RY, Donovan, C, Liu, G, Faiz, A, Short, KR, Lyons, JG, McCaughan, GW, Gorrell, MD, Cole, A, Moreno, C, Couteur, D, Hesselson, D, Triccas, J, Neely, GG, Gamble, JR, Simpson, SJ, Saunders, BM, Oliver, BG, Britton, WJ, Wark, PA, Nold-Petry, CA & Hansbro, PM 2020, 'Animal and translational models of SARS-CoV-2 infection and COVID-19', Mucosal Immunology, vol. 13, no. 6, pp. 877-891.
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COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.
Jones, PM & George, AM 2020, 'Is the emperor wearing shorts? The published structures of ABC transporters', FEBS Letters, vol. 594, no. 23, pp. 3790-3798.
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ABC transporters use the energy of ATP binding and hydrolysis to transport substrates across cellular membranes. They comprise two highly conserved nucleotide binding domains and two transmembrane domains that form the transmembrane channel and contain the substrate binding sites. Structural analyses have found a variety of seemingly unrelated folds for the ABC transporter transmembrane domains, and from these, a set of diverse mechanistic models has been inferred. Nevertheless, in spite of the explosion in structure determination of ABC transporters in the last decade, advancement in certainty and clarity as to fundamental aspects of their molecular mechanisms remains elusive. With this in mind, here we put and examine the question: Could current ABC structures differ from the physiologic membrane‐embedded forms?
Kaasalainen, S, Sussman, T, Thompson, G, McCleary, L, Hunter, PV, Venturato, L, Wickson-Griffiths, A, Ploeg, J, Parker, D, Sinclair, S, Dal Bello-Haas, V, Earl, M & You, JJ 2020, 'A pilot evaluation of the Strengthening a Palliative Approach in Long-Term Care (SPA-LTC) program', BMC Palliative Care, vol. 19, no. 1.
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AbstractBackgroundDespite increased annual mortality in long-term care (LTC) homes, research has shown that care of dying residents and their families is currently suboptimal in these settings. The purpose of this study was to evaluate resident and family outcomes associated with the Strengthening a Palliative Approach in LTC (SPA-LTC) program, developed to help encourage meaningful end of life discussions and planning.MethodsThe study employs a mixed method design in four LTC homes across Southern Ontario. Data were collected from residents and families of the LTC homes through chart reviews, interviews, and focus groups. Interviews with family who attended a Palliative Care Conference included both closed-ended and open-ended questions.ResultsIn total, 39 residents/families agreed to participate in the study. Positive intervention outcomes included a reduction in the proportion of emergency department use at end of life and hospital deaths for those participating in SPA-LTC, improved support for families, and increased family involvement in the care of residents. For families who attended a Palliative Care Conference, both quantitative and qualitative findings revealed that families benefited from attending them. Residents stated that they appreciated learning about a palliative approach to care and being informed about their current status.ConclusionsThe benefits of SPA-LTC for residents and families justify its continued use within LTC. Study results also suggest that certain enhancements of the program could further promote future integration of best practices within a palliative approach to care within the LTC context. However, the generalizability of these results across LTC homes in...
Kalkhoven, J, Coutts, AJ & Impellizzeri, FM 2020, '‘Training load error’ is not a more accurate term than ‘overuse’ injury', British Journal of Sports Medicine, vol. 54, no. 15, pp. 934-935.
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Kaluarachchi, T, McDonald, F, Patterson, P & Newton-John, TRO 2020, 'Being a teenager and cancer patient: What do adolescents and young adults with cancer find valuable and challenging with their friends and cancer peers?', Journal of Psychosocial Oncology, vol. 38, no. 2, pp. 195-209.
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© 2019, © 2019 Taylor & Francis Group, LLC. Purpose: This study examined Adolescent and Young Adult (AYA) cancer patients’ experiences with friends and cancer friends (peers) throughout their cancer journey. Research approach: Qualitative, thematic analysis. Participants: Twelve AYA diagnosed with cancer, treated within the past five years. Methodological approach: Individual semi-structured interviews, focusing on friend and peer experiences pre-/post-diagnosis, during and after treatment. Findings: Overarching themes of ‘valued’ vs. ‘challenging’ aspects with friends and peers. Interpretation: Friend and peer relationships were both valuable, but in different ways. Friends provided general support and helped AYA feel like a normal teenager, while peers provided targeted support and helped AYA feel like a normal teenager with cancer. Peers had an intimate understanding of cancer, whereas poor understanding by friends led to further challenges such as avoidance and being dismissive. Peer relations were notably challenged by a premature confrontation with mortality. Friendships evolved and changed throughout the cancer journey.
Kapeleris, J, Kulasinghe, A, Warkiani, ME, Oleary, C, Vela, I, Leo, P, Sternes, P, O’Byrne, K & Punyadeera, C 2020, 'Ex vivo culture of circulating tumour cells derived from non-small cell lung cancer', Translational Lung Cancer Research, vol. 9, no. 5, pp. 1795-1809.
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Background
Tumour tissue-based information is limited. Liquid biopsy can provide valuable real-time information through circulating tumour cells (CTCs). Profiling and expanding CTCs may provide avenues to study transient metastatic disease.
Methods
Seventy non-small cell lung cancer (NSCLC) patients were recruited. CTCs were enriched using the spiral microfluidic chip and a RosetteSep™ using bloods from NSCLC patients. CTC cultures were carried out using the Clevers media under hypoxic conditions. CTCs were characterized using immunofluorescence and mutation-specific antibodies for samples with known mutation profiles. Exome sequencing was used to characterized CTC cultures.
Results
CTCs (>2 cells) were detected in 38/70 (54.3%) of patients ranging from 0 to 385 CTCs per 7.5 mL blood. In 4/5 patients where primary tumours harboured an EGFR exon 19 deletion, this EGFR mutation was also captured in CTCs. ALK translocation was confirmed on CTCs from a patient harbouring an ALK-rearrangement in the primary tumour. Short term CTC cultures were successfully generated in 9/70 NSCLC patients. Whole exome sequencing (WES) confirmed the presence of somatic mutations in the CTC cultures with mutational signatures consistent with NSCLC.
Conclusions
We were able to detect CTCs in >50% of NSCLC patients. NSCLC patients with >2 CTCs had a poor prognosis. The short-term CTC culture success rate was 12.9%. Further optimization of this culture methodology may provide a means by which to expand CTCs derived from NSCLC patient's bloods. CTC cultures allow for expansion of cells to a critical mass, allowing for functional characterization of CTCs with the goal of drug sensitivity testing and the creation of CTC cell lines.
Kedziora, DJ, Musial, K & Gabrys, B 2020, 'AutonoML: Towards an Integrated Framework for Autonomous Machine Learning'.
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Over the last decade, the long-running endeavour to automate high-levelprocesses in machine learning (ML) has risen to mainstream prominence,stimulated by advances in optimisation techniques and their impact on selectingML models/algorithms. Central to this drive is the appeal of engineering acomputational system that both discovers and deploys high-performance solutionsto arbitrary ML problems with minimal human interaction. Beyond this, an evenloftier goal is the pursuit of autonomy, which describes the capability of thesystem to independently adjust an ML solution over a lifetime of changingcontexts. However, these ambitions are unlikely to be achieved in a robustmanner without the broader synthesis of various mechanisms and theoreticalframeworks, which, at the present time, remain scattered across numerousresearch threads. Accordingly, this review seeks to motivate a more expansiveperspective on what constitutes an automated/autonomous ML system, alongsideconsideration of how best to consolidate those elements. In doing so, we surveydevelopments in the following research areas: hyperparameter optimisation,multi-component models, neural architecture search, automated featureengineering, meta-learning, multi-level ensembling, dynamic adaptation,multi-objective evaluation, resource constraints, flexible user involvement,and the principles of generalisation. We also develop a conceptual frameworkthroughout the review, augmented by each topic, to illustrate one possible wayof fusing high-level mechanisms into an autonomous ML system. Ultimately, weconclude that the notion of architectural integration deserves more discussion,without which the field of automated ML risks stifling both its technicaladvantages and general uptake.
Khan, TA & Ling, SH 2020, 'A survey of the state-of-the-art swarm intelligence techniques and their application to an inverse design problem', Journal of Computational Electronics, vol. 19, no. 4, pp. 1606-1628.
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Khorsand, M, Tavakoli, J, Guan, H & Tang, Y 2020, 'Artificial intelligence enhanced mathematical modeling on rotary triboelectric nanogenerators under various kinematic and geometric conditions', Nano Energy, vol. 75, pp. 104993-104993.
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© 2020 Elsevier Ltd The triboelectric nanogenerator (TENG) has been introduced as a revolutionary technology in the renewable electrical energy generation at micro/nanoscale. In the current study, experimental and theoretical models for augmented rotary TENGs are presented. The power generated by TENGs is found to be a function of the number of segments, rotational speed, and tribo-surface spacing. Mathematical modeling combined with artificial intelligence is applied to characterize the TENG output under various kinematics and geometric conditions. Sensitivity analysis reveals that the generated energy and the matched resistance depend highly on segmentation and angular velocity rate. It is shown that the optimized harvested energy reaches 0.369 mJ at each cycle. The TENG dynamic outputs for various structural parameters are found and described. This study enhances understanding of rotation-induced periodic TENGs and reveals optimized characteristics for disk-shaped TENG energy harvesters.
Khuat, TT & Gabrys, B 2020, 'Accelerated learning algorithms of general fuzzy min-max neural network using a novel hyperbox selection rule', Information Sciences, vol. 547, pp. 887-909.
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This paper proposes a method to accelerate the training process of a generalfuzzy min-max neural network. The purpose is to reduce the unsuitablehyperboxes selected as the potential candidates of the expansion step ofexisting hyperboxes to cover a new input pattern in the online learningalgorithms or candidates of the hyperbox aggregation process in theagglomerative learning algorithms. Our proposed approach is based on themathematical formulas to form a branch-and-bound solution aiming to remove thehyperboxes which are certain not to satisfy expansion or aggregationconditions, and in turn, decreasing the training time of learning algorithms.The efficiency of the proposed method is assessed over a number of widely useddata sets. The experimental results indicated the significant decrease intraining time of the proposed approach for both online and agglomerativelearning algorithms. Notably, the training time of the online learningalgorithms is reduced from 1.2 to 12 times when using the proposed method,while the agglomerative learning algorithms are accelerated from 7 to 37 timeson average.
Khuat, TT & Gabrys, B 2020, 'Random Hyperboxes', IEEE Transactions on Neural Networks and Learning Systems (2021).
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This paper proposes a simple yet powerful ensemble classifier, called RandomHyperboxes, constructed from individual hyperbox-based classifiers trained onthe random subsets of sample and feature spaces of the training set. We alsoshow a generalization error bound of the proposed classifier based on thestrength of the individual hyperbox-based classifiers as well as thecorrelation among them. The effectiveness of the proposed classifier isanalyzed using a carefully selected illustrative example and comparedempirically with other popular single and ensemble classifiers via 20 datasetsusing statistical testing methods. The experimental results confirmed that ourproposed method outperformed other fuzzy min-max neural networks, popularlearning algorithms, and is competitive with other ensemble methods. Finally,we identify the existing issues related to the generalization error bounds ofthe real datasets and inform the potential research directions.
Kochovska, S, Ferreira, DH, Luckett, T, Phillips, JL & Currow, DC 2020, 'Earlier multidisciplinary palliative care intervention for people with lung cancer: a systematic review and meta-analysis', Translational Lung Cancer Research, vol. 9, no. 4, pp. 1699-1709.
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Lung cancer is the most common cancer and leading cause of cancer mortality globally. Lung cancer is associated with significant morbidity, with symptoms often being poorly managed, causing significant symptom burden for both patients and their family caregivers. In people with life-limiting illnesses including advanced cancer, palliative care has been effective in improving symptom control, physical and mental wellbeing, quality of life, and survivorship; with benefits extending to caregivers while in the role and subsequently. Earlier integration of palliative care within oncology may be associated with improved patient outcomes, and has been supported by two Lancet commissions and national guidelines. The evidence for its effectiveness, however, has been mixed across the cancer spectrum. The aim of this review was to evaluate the current evidence for the effectiveness of early integrated palliative care in improving outcomes for people with lung cancer and their caregivers. Meta-analyses were performed where studies used the same measure. Otherwise, synthesis used a narrative approach. Similar to other types of advanced cancer, this review reveals mixed evidence for the effectiveness of early referral to palliative care and for the effectiveness of individual palliative interventions for people with lung cancer and their caregivers. Evidence that on-demand palliative care is equally, if not more effective than palliative care that is routinely provided, raises the question whether initiation and provision of palliative care as part of multidisciplinary lung cancer care ought to be guided by an early referral or need-based referral. Better understanding of what constitutes palliative care when delivered to people with lung cancer and their caregivers will help delineate the correlation with reported outcomes for these populations.
Kochovska, S, Garcia, MV, Bunn, F, Goodman, C, Luckett, T, Parker, D, Phillips, JL, Sampson, EL, van der Steen, JT & Agar, MR 2020, 'Components of palliative care interventions addressing the needs of people with dementia living in long-term care: A systematic review', Palliative Medicine, vol. 34, no. 4, pp. 454-492.
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Background: People with dementia requiring palliative care have multiple needs, which are amplified in long-term care settings. The European Association for Palliative Care White Paper offers recommendations for optimal palliative care in dementia integral for this population, providing useful guidance to inform interventions addressing their specific needs. Aim: The aim of this study is to describe the components of palliative care interventions for people with dementia in long-term care focusing on shared decision-making and examine their alignment to the European Association for Palliative Care domains of care. Design: Systematic review with narrative synthesis (PROSPERO ID: CRD42018095649). Data sources: Four databases (MEDLINE, CINAHL, PsycINFO and CENTRAL) were searched (earliest records – July 2019) for peer-reviewed articles and protocols in English, reporting on palliative care interventions for people with dementia in long-term care, addressing European Association for Palliative Care Domains 2 (person-centred) or 3 (setting care goals) and ⩾1 other domain. Results: Fifty-one papers were included, reporting on 32 studies. For each domain (1–10), there were interventions found aiming to address its goal, although no single intervention addressed all domains. Domain 7 (symptom management; n = 19), 6 (avoiding overly aggressive treatment; n = 18) and 10 (education; n = 17) were the most commonly addressed; Domain 5 (prognostication; n = 7) and 4 (continuity of care; n = 2) were the least addressed. Conclusion: Almost all domains were addressed across all interventions currently offered for this ...
Komalla, V, Allam, VSRR, Kwok, PCL, Sheikholeslami, B, Owen, L, Jaffe, A, Waters, SA, Mohammad, S, Oliver, BG, Chen, H & Haghi, M 2020, 'A phospholipid-based formulation for the treatment of airway inflammation in chronic respiratory diseases', European Journal of Pharmaceutics and Biopharmaceutics, vol. 157, pp. 47-58.
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Komalla, V, Sheikholeslami, B, Li, G, Bokshi, B, Chan, YL, Ung, A, Gregory Oliver, B, Chen, H & Haghi, M 2020, 'Impact of A Cargo-Less Liposomal Formulation on Dietary Obesity-Related Metabolic Disorders in Mice', International Journal of Molecular Sciences, vol. 21, no. 20, pp. 7640-7640.
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Current therapeutic options for obesity often require pharmacological intervention with dietary restrictions. Obesity is associated with underlying inflammation due to increased tissue macrophage infiltration, and recent evidence shows that inflammation can drive obesity, creating a feed forward mechanism. Therefore, targeting obesity-induced macrophage infiltration may be an effective way of treating obesity. Here, we developed cargo-less liposomes (UTS-001) using 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC (synthetic phosphatidylcholine) as a single-agent to manage weight gain and related glucose disorders due to high fat diet (HFD) consumption in mice. UTS-001 displayed potent immunomodulatory properties, including reducing resident macrophage number in both fat and liver, downregulating liver markers involved in gluconeogenesis, and increasing marker involved in thermogenesis. As a result, UTS-001 significantly enhanced systemic glucose tolerance in vivo and insulin-stimulated cellular glucose uptake in vitro, as well as reducing fat accumulation upon ad libitum HFD consumption in mice. UTS-001 targets tissue residence macrophages to suppress tissue inflammation during HFD-induced obesity, resulting in improved weight control and glucose metabolism. Thus, UTS-001 represents a promising therapeutic strategy for body weight management and glycaemic control.
Kong, AC, George, A, Villarosa, AR, Agar, M, Harlum, J, Wiltshire, J, Srinivas, R & Parker, D 2020, 'Perceptions of nurses towards oral health in palliative care: A qualitative study', Collegian, vol. 27, no. 5, pp. 499-505.
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© 2020 Australian College of Nursing Ltd. Background: Oral health problems among people receiving palliative care are common and can significantly affect quality of life. Nurses are at the frontline of palliative care in Australia. However, how optimal oral health care is addressed in clinical practice by palliative nurses is not known. Aim: To explore the perceptions of nurses working in Australian palliative care settings to determine the acceptability, challenges and recommendations that need to be considered to develop and implement an oral health care model in palliative care settings. Methods: Two focus groups were conducted with community (n = 8) and inpatient nurses (n = 10) working in urban palliative care settings. Findings: Four main themes were developed through consensus: 1) Oral health is important in the palliative care setting; 2) Additional training could enhance what nurses already do; 3) Barriers to receiving oral care: a structural issue; 4) Exploring alternative pathways to dental services. Discussion: Nurses recognised the importance of oral health in palliative care; however, the paucity of set protocols based on existing guidelines meant that oral care was often unstructured. Systemic factors reduced the number of available options for people receiving palliative care to access professional dental treatment. Although alternative solutions, including teledentistry services, were explored, there were some constraints. Conclusion: A palliative care oral health model of care would need to integrate existing formal guidelines into a comprehensive framework specific for palliative care nurses and develop palliative care oral health training for them taking into consideration existing barriers for people to receive professional dental treatment.
Kramer, I, Hooning, MJ, Mavaddat, N, Hauptmann, M, Keeman, R, Steyerberg, EW, Giardiello, D, Antoniou, AC, Pharoah, PDP, Canisius, S, Abu-Ful, Z, Andrulis, IL, Anton-Culver, H, Aronson, KJ, Augustinsson, A, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Bremer, M, Brucker, SY, Burwinkel, B, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Choi, J-Y, Clarke, CL, Collée, JM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Evans, DG, Fasching, PA, Flyger, H, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Giles, GG, Goldgar, DE, González-Neira, A, Haiman, CA, Håkansson, N, Hamann, U, Hartman, M, Heemskerk-Gerritsen, BAM, Hollestelle, A, Hopper, JL, Hou, M-F, Howell, A, Ito, H, Jakimovska, M, Jakubowska, A, Janni, W, John, EM, Jung, A, Kang, D, Kets, CM, Khusnutdinova, E, Ko, Y-D, Kristensen, VN, Kurian, AW, Kwong, A, Lambrechts, D, Le Marchand, L, Li, J, Lindblom, A, Lubiński, J, Mannermaa, A, Manoochehri, M, Margolin, S, Matsuo, K, Mavroudis, D, Meindl, A, Milne, RL, Mulligan, AM, Muranen, TA, Neuhausen, SL, Nevanlinna, H, Newman, WG, Olshan, AF, Olson, JE, Olsson, H, Park-Simon, T-W, Peto, J, Petridis, C, Plaseska-Karanfilska, D, Presneau, N, Pylkäs, K, Radice, P, Rennert, G, Romero, A, Roylance, R, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schwentner, L, Scott, C, See, M-H, Shah, M, Shen, C-Y, Shu, X-O, Siesling, S, Slager, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tapper, WJ, Tengström, M, Teo, SH, Terry, MB, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Vachon, CM, van Ongeval, C, van Veen, EM, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Easton, DF, Hall, P, Schmidt, MK, Børresen-Dale, A-L, Sahlberg, K, Ottestad, L, Kåresen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebråten, O, Naume, B, Fosså, A, Kiserud, C, Reinertsen, K, Helland, Å, Riis, M, Geisler, J, Alnæs, GG, Clarke, C, Marsh, D, Scott, R, Baxter, R, Yip, D, Carpenter, J, Davis, A, Pathmanathan, N, Simpson, P, Graham, JD, Sachchithananthan, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Bennett, I, Bogwitz, M, Botes, L, Brennan, M, Brown, M, Buckley, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Chauhan, D, Chauhan, M, Chenevix-Trench, G & et al. 2020, 'Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk', The American Journal of Human Genetics, vol. 107, no. 5, pp. 837-848.
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Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
Kulasinghe, A, Lim, Y, Kapeleris, J, Warkiani, M, O’Byrne, K & Punyadeera, C 2020, 'The Use of Three-Dimensional DNA Fluorescent In Situ Hybridization (3D DNA FISH) for the Detection of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer (NSCLC) Circulating Tumor Cells', Cells, vol. 9, no. 6, pp. 1465-1465.
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Tumor tissue biopsy is often limited for non-small cell lung cancer (NSCLC) patients and alternative sources of tumoral information are desirable to determine molecular alterations such as anaplastic lymphoma kinase (ALK) rearrangements. Circulating tumor cells (CTCs) are an appealing component of liquid biopsies, which can be sampled serially over the course of treatment. In this study, we enrolled a cohort of ALK-positive (n = 8) and ALK-negative (n = 12) NSCLC patients, enriched for CTCs using spiral microfluidic technology and performed DNA fluorescent in situ hybridization (FISH) for ALK. CTCs were identified in 12/20 NSCLC patients ranging from 1 to 26 CTCs/7.5 mL blood. Our study revealed that 3D imaging of CTCs for ALK translocations captured a well-defined separation of 3′ and 5′ signals indicative of ALK translocations and overlapping 3′/5′ signal was easily resolved by imaging through the nuclear volume. This study provides proof-of-principle for the use of 3D DNA FISH in the determination of CTC ALK translocations in NSCLC.
La, QT, Ren, B, Logan, GJ, Cunningham, SC, Khandekar, N, Nassif, NT, O’Brien, BA, Alexander, IE & Simpson, AM 2020, 'Use of a Hybrid Adeno-Associated Viral Vector Transposon System to Deliver the Insulin Gene to Diabetic NOD Mice', Cells, vol. 9, no. 10, pp. 2227-2227.
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Previously, we used a lentiviral vector to deliver furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (PT), due to the expression of beta (β)-cell transcription factors (β-TFs). The present study aimed to determine whether we could similarly reverse diabetes in the non-obese diabetic (NOD) mouse using an adeno-associated viral vector (AAV) to deliver INS-FUR ± the β-TF Pdx1 to the livers of diabetic mice. The traditional AAV8, which provides episomal expression, and the hybrid AAV8/piggyBac that results in transgene integration were used. Diabetic mice that received AAV8-INS-FUR became hypoglycaemic with abnormal intraperitoneal glucose tolerance tests (IPGTTs). Expression of β-TFs was not detected in the livers. Reversal of diabetes was not achieved in mice that received AAV8-INS-FUR and AAV8-Pdx1 and IPGTTs were abnormal. Normoglycaemia and glucose tolerance were achieved in mice that received AAV8/piggyBac-INS-FUR/FFO. Definitive evidence of PT was not observed. This is the first in vivo study using the hybrid AAV8/piggyBac system to treat Type 1 diabetes (T1D). However, further development is required before the system can be used for gene therapy of T1D.
Lazar, S, Rayner, B, Lopez Campos, G, McGrath, K & McClements, L 2020, 'Mechanisms of heart failure with preserved ejection fraction in the presence of diabetes mellitus', Translational Metabolic Syndrome Research, vol. 3, pp. 1-5.
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Cardiovascular disease (CVD) is the leading cause of death globally. People living with type 2 diabetes mellitus (T2DM) have a three times higher risk of developing CVD, particularly heart failure with preserved ejection fraction (HFpEF), for which there is no treatment. The need for tangible interventions has led to investigations into a number of biomarkers associated with metabolic and vascular dysfunction that could be utilised for diagnostic and treatment purposes. This review discusses the importance and mechanisms of inflammatory and angiogenic biomarkers, which have shown the most potential in the pathogenesis and diagnosis of HFpEF in the presence of diabetes. In
depth “in silico” analysis was also carried out to identify pathogenic pathways associated with HFpEF, both in the presence and absence of diabetes. The results identified mostly inflammatory pathways associated with HFpEF in the presence of diabetes, and a number of pathways related to angiogenesis, remodelling and metabolism. In addition, the results also identified inflammation, in the absence of diabetes. The shared and unique pathways identified in HFpEF in the presence and
absence of diabetes, should be explored further in order to improve management and outcomes of people living with HFpEF.
Lee, H, Phillips, JB, Hall, RM & Tipper, JL 2020, 'Neural cell responses to wear debris from metal-on-metal total disc replacements', European Spine Journal, vol. 29, no. 11, pp. 2701-2712.
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PurposeAbstractTotal disc replacements, comprising all-metal articulations, are compromised by wear and particle production. Metallic wear debris and ions trigger a range of biological responses including inflammation, genotoxicity, cytotoxicity, hypersensitivity and pseudotumour formation, therefore we hypothesise that, due to proximity to the spinal cord, glial cells may be adversely affected.MethodsClinically relevant cobalt chrome (CoCr) and stainless steel (SS) wear particles were generated using a six-station pin-on-plate wear simulator. The effects of metallic particles (0.5–50 μm3 debris per cell) and metal ions on glial cell viability, cellular activity (glial fibrillary acidic protein (GFAP) expression) and DNA integrity were investigated in 2D and 3D culture using live/dead, immunocytochemistry and a comet assay, respectively.ResultsCoCr wear particles and ions caused significant reductions in glial cell viability in both 2D and 3D culture systems. Stainless steel particles did not affect glial cell viability or astrocyte activation. In contrast, ions released from SS caused significant reductions in glial cell viability, an effect that was especially noticeable when astrocytes were cultured in isolation without microglia. DNA damage was observed in both cell types and with both biomaterials tested. CoCr wear particles had a dose-dependent effect on astrocyte activation, measured through expression of GFAP.ConclusionsThe results from this study suggest that microglia influence the effects that metal particles have on astrocytes, that SS ions and particles play a role in the adverse effects observed and that SS is a less toxic biomaterial than CoCr alloy f...
Lees, T, Maharaj, S, Kalatzis, G, Nassif, NT, Newton, PJ & Lal, S 2020, 'Electroencephalographic prediction of global and domain specific cognitive performance of clinically active Australian Nurses', Physiological Measurement, vol. 41, no. 9, pp. 095001-095001.
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Abstract Objective: To investigate the relationship between EEG activity and the global and domain specific cognitive performance of healthy nurses, and determine the predictive capabilities of these relationships. Approach: Sixty-four nurses were recruited for the present study, and data from 61 were utilised in the present analysis. Global and domain specific cognitive performance of each participant was assessed psychometrically using the Mini-mental state exam and the Cognistat, and a 32-lead monopolar EEG was recorded during a resting baseline phase and an active phase in which participants completed the Stroop test. Main results: Global cognitive performance was successfully predicted (81%–85% of variance) by a combination of fast wave activity variables in the alpha, beta and theta frequency bands. Interestingly, predicting domain specific performance had varying degrees of success (42%–99% of the variance predicted) and relied on combinations of both slow and fast wave activity, with delta and gamma activity predicting attention performance; delta, theta, and gamma activity predicting memory performance; and delta and beta variables predicting judgement performance. Significance: Global and domain specific cognitive performance of Australian nurses may be predicted with varying degrees of success by a unique combination of EEG variables. These proposed models image transitory cognitive declines and as such may prove useful in the prediction of early cognitive impairment, and may enable better diagnosis, and management of cognitive impairment.
Li, G, Chan, YL, Wang, B, Saad, S, George, J, Oliver, BG & Chen, H 2020, 'E‐cigarettes damage the liver and alter nutrient metabolism in pregnant mice and their offspring', Annals of the New York Academy of Sciences, vol. 1475, no. 1, pp. 64-77.
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AbstractApproximately 15% of pregnant women vape electronic cigarettes (e‐cigarettes), exposing the fetus to a range of toxic compounds, including nicotine and by‐products of e‐cigarette liquid (e‐liquid) pyrolysis. Owing to the recent emergence of these products, research mainly focuses on immediate users, and not on in utero exposure. Therefore, this study aimed to understand the impact of intrauterine e‐cigarette vapor (e‐vapor) exposure, with and without nicotine, on liver metabolic markers in the male offspring. E‐vapor was generated using an e‐cigarette filled with tobacco‐flavored e‐liquid (18 or 0 mg/mL nicotine). Female Balb/c mice were exposed to e‐vapor for 6 weeks before mating, through gestation and lactation, without direct exposure to the offspring. Livers and plasma from dams and male offspring (13 weeks old) were examined. Exposure to nicotine‐free e‐vapor promoted metabolic changes and liver damage in both the dams and their offspring. Furthermore, exposure to nicotine‐containing e‐vapor did not cause liver damage but induced hepatic steatosis in the adult offspring. Therefore, maternal vaping is detrimental to both the dams and their offspring, with nicotine providing a potential protective effect.
Li, G, Chan, YL, Wang, B, Saad, S, Oliver, BG & Chen, H 2020, 'Replacing smoking with vaping during pregnancy: Impacts on metabolic health in mice', Reproductive Toxicology, vol. 96, pp. 293-299.
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Smoking is a significant risk factor for the development of metabolic diseases. Due to social pressures to quit smoking, many pregnant women are vaping as an alternative nicotine source. However, the metabolic consequences of replacing tobacco cigarettes with e-cigarettes during pregnancy are unknown. Therefore, in the mothers and their offspring, we investigated the metabolic and hepatic impacts of replacing cigarette smoke with e-vapour during pregnancy. Female BALB/c mice were either air-exposed or cigarette smoke-exposed (SE) from six weeks before pregnancy until lactation. At mating, a subset of the SE mice were instead exposed to e-vapour. Markers of glucose and lipid metabolism were measured in the livers and plasma, from the mothers and their male offspring (13 weeks). In the SE mothers, plasma insulin levels were reduced, leading to downstream increases in hepatic gluconeogenesis and plasma non-esterified fatty acids (NEFA). In the e-vapour replacement mothers, these changes were not as significant. In the SE offspring, there was impaired glucose tolerance, and increased plasma NEFA and liver triglyceride concentrations. E-vapour replacement restored lipid homeostasis but did not improve glucose tolerance. Therefore, in a murine model, low dose e-cigarette replacement during pregnancy is less toxic than cigarette smoke.
Li, S, Watterson, PA, Li, Y, Wen, Q & Li, J 2020, 'Improved magnetic circuit analysis of a laminated magnetorheological elastomer device featuring both permanent magnets and electromagnets', Smart Materials and Structures, vol. 29, no. 8, pp. 085054-085054.
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As an essential and critical step, magnetic circuit modelling is usually implemented in the design of efficient and compact magnetorheological (MR) devices, such as MR dampers and MR elastomer isolators. Conventional magnetic circuit analysis simplifies the analysis by ignoring the magnetic flux leakage and magnetic fringing effect. These assumptions are sufficiently accurate in dealing with less complicated designs, featuring short magnetic path lengths such as in an MR damper. However, when dealing with MR elastomer devices, such simplification in magnetic circuit analysis results in inaccuracy of dimensioning and performance estimation of the devices due to their sophisticated design and complex magnetic paths. Modelling permanent magnets also imposes challenges in the magnetic circuit analysis. This work proposes an improved approach to include magnetic flux fringing effect in magnetic circuit analysis for MR elastomer devices. An MRE-based isolator containing multiple MRE layers and both a permanent magnet and an exciting coil was designed and built as a case study. The results of the proposed method are compared to those of conventional magnetic circuit modelling, finite element analysis and experimental measurements to demonstrate the effectiveness of the proposed approach.
Li, X, Ling, SH & Su, S 2020, 'A Hybrid Feature Selection and Extraction Methods for Sleep Apnea Detection Using Bio-Signals', Sensors, vol. 20, no. 15, pp. 4323-4323.
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People with sleep apnea (SA) are at increased risk of having stroke and cardiovascular diseases. Polysomnography (PSG) is used to detect SA. This paper conducts feature selection from PSG signals and uses a support vector machine (SVM) to detect SA. To analyze SA, the Physionet Apnea Database was used to obtain various features. Electrocardiography (ECG), oxygen saturation (SaO2), airflow, abdominal, and thoracic signals were used to provide various frequency-, time-domain and non-linear features (n = 87). To analyse the significance of these features, firstly, two evaluation measures, the rank-sum method and the analysis of variance (ANOVA) were used to evaluate the significance of the features. These features were then classified according to their significance. Finally, different class feature sets were presented as inputs for an SVM classifier to detect the onset of SA. The hill-climbing feature selection algorithm and the k-fold cross-validation method were applied to evaluate each classification performance. Through the experiments, we discovered that the best feature set (including the top-five significant features) obtained the best classification performance. Furthermore, we plotted receiver operating characteristic (ROC) curves to examine the performance of the SVM, and the results showed the SVM with Linear kernel (regularization parameter = 1) outperformed other classifiers (area under curve = 95.23%, sensitivity = 94.29%, specificity = 96.17%). The results confirm that feature subsets based on multiple bio-signals have the potential to identify patients with SA. The use of a smaller subset avoids dimensionality problems and reduces the computational load.
Liu, J, Prager - van der Smissen, WJC, Collée, JM, Bolla, MK, Wang, Q, Michailidou, K, Dennis, J, Ahearn, TU, Aittomäki, K, Ambrosone, CB, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Arnold, N, Aronson, KJ, Augustinsson, A, Auvinen, P, Becher, H, Beckmann, MW, Behrens, S, Bermisheva, M, Bernstein, L, Bogdanova, NV, Bogdanova-Markov, N, Bojesen, SE, Brauch, H, Brenner, H, Briceno, I, Brucker, SY, Brüning, T, Burwinkel, B, Cai, Q, Cai, H, Campa, D, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Christiaens, M, Clarke, CL, Sahlberg, KK, Børresen-Dale, A-L, Ottestad, L, Kåresen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebråten, O, Naume, B, Fosså, A, Kiserud, CE, Reinertsen, KV, Helland, Å, Riis, M, Geisler, J, Bathen, TF, Borgen, E, Fritzman, B, Garred, Ø, Geitvik, GA, Hofvind, S, Langerød, A, Lingjærde, OC, Mælandsmo, GM, Russnes, HG, Skjerven, HK, Sørlie, T, Alnæs, GIG, Couch, FJ, Czene, K, Daly, MB, Devilee, P, dos-Santos-Silva, I, Dwek, M, Eccles, DM, Eliassen, AH, Fasching, PA, Figueroa, J, Flyger, H, Fritschi, L, Gago-Dominguez, M, Gapstur, SM, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, Goldgar, DE, Guénel, P, Haiman, CA, Håkansson, N, Hall, P, Harrington, PA, Hart, SN, Hartman, M, Hillemanns, P, Hopper, JL, Hou, M-F, Hunter, DJ, Huo, D, Clarke, C, Marsh, D, Scott, R, Baxter, R, Yip, D, Carpenter, J, Davis, A, Pathmanathan, N, Simpson, P, Graham, D, Sachchithananthan, M, Ito, H, Iwasaki, M, Jakimovska, M, Jakubowska, A, John, EM, Kaaks, R, Kang, D, Keeman, R, Khusnutdinova, E, Kim, S-W, Kraft, P, Kristensen, VN, Kurian, AW, Le Marchand, L, Li, J, Lindblom, A, Lophatananon, A, Luben, RN, Lubiński, J, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Mariapun, S, Matsuo, K, Maurer, T, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Muir, K, Mulligan, AM, Neuhausen, SL, Nevanlinna, H, Offit, K, Olopade, OI, Olson, JE, Olsson, H, Orr, N, Park, SK, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Rack, B, Rau-Murthy, R, Rennert, G, Rennert, HS, Rhenius, V, Romero, A, Ruebner, M, Saloustros, E, Schmutzler, RK, Schneeweiss, A, Scott, C, Shah, M, Shen, C-Y, Shu, X-O, Simard, J, Sohn, C, Southey, MC, Spinelli, JJ, Tamimi, RM, Tapper, WJ, Teo, SH, Terry, MB, Torres, D, Truong, T, Untch, M, Vachon, CM, van Asperen, CJ, Wolk, A & et al. 2020, 'Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk', Scientific Reports, vol. 10, no. 1, p. 9688.
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AbstractIn breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Liu, T, Zhang, W, Yuwono, M, Zhang, M, Ueland, M, Forbes, SL & Su, SW 2020, 'A data-driven meat freshness monitoring and evaluation method using rapid centroid estimation and hidden Markov models', Sensors and Actuators B: Chemical, vol. 311, pp. 127868-127868.
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Liu, Y, Lan, C, Blumenstein, M & Li, J 2020, 'Bi-Level Error Correction for PacBio Long Reads', IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 17, no. 3, pp. 899-905.
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IEEE The latest sequencing technologies such as the Pacific Biosciences (PacBio) and Oxford Nanopore machines can generate long reads at the length of thousands of nucleic bases which is much longer than the reads at the length of hundreds generated by Illumina machines. However, these long reads are prone to much higher error rates, for example 15%, making downstream analysis and applications very difficult. Error correction is a process to improve the quality of sequencing data. Hybrid correction strategies have been recently proposed to combine Illumina reads of low error rates to fix sequencing errors in the noisy long reads with good performance. In this paper, we propose a new method named Bicolor, a bi-level framework of hybrid error correction for further improving the quality of PacBio long reads. At the first level, our method uses a de Bruijn graph-based error correction idea to search paths in pairs of solid < formula > < tex > $k$ < /tex > < /formula > -mers iteratively with an increasing length of < formula > < tex > $k$ < /tex > < /formula > -mer. At the second level, we combine the processed results under different parameters from the first level. In particular, a multiple sequence alignment algorithm is used to align those similar long reads, followed by a voting algorithm which determines the final base at each position of the reads. We compare the superior performance of Bicolor with three state-of-the-art methods on three real data sets. Results demonstrate that Bicolor always achieves the highest identity ratio. Bicolor also achieves a higher alignment ratio ( < formula > < tex > $ & #x003E; 1.3\%$ < /tex > < /formula > ) and a higher number of aligned reads than the current methods on two data sets. On the third data set, our method is closely competitive to the current methods in terms of number of aligned reads and genome coverage. The C++ source codes of our algorithm are freely available at https://github.com/yuansliu/Bicolor.
Liu, Y, Wong, L & Li, J 2020, 'Allowing mutations in maximal matches boosts genome compression performance', Bioinformatics, vol. 36, no. 18, pp. 4675-4681.
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Abstract Motivation A maximal match between two genomes is a contiguous non-extendable sub-sequence common in the two genomes. DNA bases mutate very often from the genome of one individual to another. When a mutation occurs in a maximal match, it breaks the maximal match into shorter match segments. The coding cost using these broken segments for reference-based genome compression is much higher than that of using the maximal match which is allowed to contain mutations. Results We present memRGC, a novel reference-based genome compression algorithm that leverages mutation-containing matches (MCMs) for genome encoding. MemRGC detects maximal matches between two genomes using a coprime double-window k-mer sampling search scheme, the method then extends these matches to cover mismatches (mutations) and their neighbouring maximal matches to form long and MCMs. Experiments reveal that memRGC boosts the compression performance by an average of 27% in reference-based genome compression. MemRGC is also better than the best state-of-the-art methods on all of the benchmark datasets, sometimes better by 50%. Moreover, memRGC uses much less memory and de-compression resources, while providing comparable compression speed. These advantages are of significant benefits to genome data storage and transmission. Availability and implementation https://github.com/yuansliu/memRGC. Supplementary information Supplementary data are available at Bioinformatics online.
Lovell, R, Halley, S, Siegler, J, Wignell, T, Coutts, AJ & Massard, T 2020, 'Use of Numerically Blinded Ratings of Perceived Exertion in Soccer: Assessing Concurrent and Construct Validity', International Journal of Sports Physiology and Performance, vol. 15, no. 10, pp. 1430-1436.
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Purpose: To examine the concurrent and construct validity of numerically blinded ratings of perceived exertion (RPEs). Methods: A total of 30 elite male youth soccer players (age 16.7 [0.5] y) were monitored during training and matches over a 17-wk in-season period. The players’ external loads were determined via raw 10-Hz global positioning system. Heart rate (HR) was collected continuously and expressed as Bannister and Edwards training impulses, and minutes >80% of the players predetermined the maximum HR by the Yo-Yo Intermittent Recovery Test Level 1. RPE was collected confidentially 10 to 15 min after training/matches using 2 methods: (1) a traditional verbal response to the 0 to 100 category-ratio “centiMax” scale (RPE) and (2) numerically blinded RPE centiMax scale (RPEblind) with the response selected manually via a 5 × 7-in tablet “slider.” The RPE and RPEblind were divided by 10 and multiplied by the duration to derive the sessional RPE. Linear mixed models compared ratings, and within-subject repeated-measures correlations assessed the sessional RPE versus HR and external load associations. Results: There were no differences between the RPE and RPEblind (0.19; 95% confidence intervals, −0.59 to 0.20 au, P = .326) or their session values (13.5; 95% confidence intervals, −17.0 to 44.0 au, P = .386), and the ratings were nearly perfectly correlated (r = .96). The associations between the sessional RPE versus HR and external load metrics were large to very large (r = .65–.81), with no differences between the RPE methods (P ≥ .50). The RPEblind also reduced verbal anchor cl...
Luckett, T, Newton-John, T, Phillips, J, Holliday, S, Giannitrapani, K, Powell-Davies, G, Lovell, M, Liauw, W, Rowett, D, Pearson, S-A, Raymond, B, Heneka, N & Lorenz, K 2020, 'Risk of opioid misuse in people with cancer and pain and related clinical considerations: a qualitative study of the perspectives of Australian general practitioners', BMJ Open, vol. 10, no. 2, pp. e034363-e034363.
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ObjectiveTo explore the perspectives of general practitioners (GPs) concerning the risk of opioid misuse in people with cancer and pain and related clinical considerations.DesignA qualitative approach using semistructured telephone interviews. Analysis used an integrative approach.SettingPrimary care.ParticipantsAustralian GPs with experience of prescribing opioids for people with cancer and pain.ResultsTwenty-two GPs participated, and three themes emerged. Theme 1 (Misuse is not the main problem) contextualised misuse as a relatively minor concern compared with pain control and toxicity, and highlighted underlying systemic factors, including limitations in continuity of care and doctor expertise. Theme 2 (‘A different mindset’ for cancer pain) captured participants’ relative comfort in prescribing opioids for pain in cancer versus non-cancer contexts, and acknowledgement that compassion and greater perceived community acceptance were driving factors, in addition to scientific support for mechanisms and clinical efficacy. Participant attitudes towards prescribing for people with cancer versus non-cancer pain differed most when cancer was in the palliative phase, when they were unconcerned by misuse. Participants were equivocal about the risk–benefit ratio of long-term opioid therapy in the chronic phase of cancer, and were reluctant to prescribe for disease-free survivors. Theme 3 (‘The question is always, ‘how lazy have you been?’) captured participants’ acknowledgement that they sometimes prescribed opioids for cancer pain as a default, easier option compared with more holistic pain...
Luckett, T, San Martin, A, Currow, DC, Johnson, MJ, Barnes-Harris, MMM & Phillips, JL 2020, 'A systematic review and meta-analysis of studies comparing burden from lung cancer and chronic obstructive pulmonary disease', Palliative Medicine, vol. 34, no. 10, pp. 1291-1304.
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Background: Chronic obstructive pulmonary disease and lung cancer are both life-limiting diseases that confer burden in the form of symptoms and affect functioning and quality of life. Comparing burden between these diseases is of interest to determine whether people with chronic obstructive pulmonary disease require improved access to Specialist Palliative Care. Access should be based on needs rather than diagnosis or prognosis but is limited for people with chronic obstructive pulmonary disease compared to lung cancer. Aim: The aim of this study was to synthesise research comparing burden from chronic obstructive pulmonary disease and lung cancer to estimate relative need for Specialist Palliative Care. Design: A systematic review was conducted of observational quantitative studies published in English peer-reviewed journals comparing burden from chronic obstructive pulmonary disease and lung cancer (PROSPERO CRD42018108819). No limits were placed on disease stage. Meta-analyses were performed where studies used the same measure; otherwise, synthesis used a narrative approach. Risk of bias was assessed using the Agency for Healthcare Research and Quality tool. Data sources: Electronic databases were searched in September 2019. Results: Of 790 articles returned, 13 were included, reporting 11 studies. Risk of bias was generally moderate. Except for pain, burden tended to be at least as substantial from chronic obstructive pulmonary disease as from lung cancer, with breathlessness and impacts on functioning being significantly worse. Longitudinal studies suggest that people with chronic obstructive pulmonary disease live with burden for longer.
Lyu, J, Bi, X & Ling, SH 2020, 'Multi-Level Cross Residual Network for Lung Nodule Classification', Sensors, vol. 20, no. 10, pp. 2837-2837.
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Computer-aided algorithm plays an important role in disease diagnosis through medical images. As one of the major cancers, lung cancer is commonly detected by computer tomography. To increase the survival rate of lung cancer patients, an early-stage diagnosis is necessary. In this paper, we propose a new structure, multi-level cross residual convolutional neural network (ML-xResNet), to classify the different types of lung nodule malignancies. ML-xResNet is constructed by three-level parallel ResNets with different convolution kernel sizes to extract multi-scale features of the inputs. Moreover, the residuals are connected not only with the current level but also with other levels in a crossover manner. To illustrate the performance of ML-xResNet, we apply the model to process ternary classification (benign, indeterminate, and malignant lung nodules) and binary classification (benign and malignant lung nodules) of lung nodules, respectively. Based on the experiment results, the proposed ML-xResNet achieves the best results of 85.88% accuracy for ternary classification and 92.19% accuracy for binary classification, without any additional handcrafted preprocessing algorithm.
Mahmoudi, T, Pirpour Tazehkand, A, Pourhassan-Moghaddam, M, Alizadeh-Ghodsi, M, Ding, L, Baradaran, B, Razavi Bazaz, S, Jin, D & Ebrahimi Warkiani, M 2020, 'PCR-free paper-based nanobiosensing platform for visual detection of telomerase activity via gold enhancement', Microchemical Journal, vol. 154, pp. 104594-104594.
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© 2020 Elsevier B.V. Telomerase activity has been demonstrated in a wide variety of most solid tumors and considered as a well-known cancer biomarker. The commonly utilized method for its detection is polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP). However, the TRAP technique suffers from false-negative results caused by the failure of PCR step. Moreover, it requires advanced equipment with a tedious and time-consuming procedure. Herein, we presented a portable nitrocellulose paper-based nanobiosensing platform for ultrafast and equipment-free detection of telomerase activity based on a simple colorimetric assay that enabled naked-eye visualization of the color change in response to enzyme activity. In this platform, hybridization was initially performed between telomere complementary oligonucleotide immobilized on gold nanoparticles (GNPs) and telomerase elongated biotinylated probe. Thereafter, the assembly was attached on activated paper strip via avidin-biotin interaction. The signal amplification was carried out by enlargement of the attached GNPs on the paper strip, forming tightly compact rod-shaped submicron structures of gold representing a visual color formation. Thanks to significant sensitivity enhancement, the color change was occurred for down to 6 cells, which can be easily observed by the naked eye. Due to the desired aspects of the developed assay including PCR-free, low cost, simple, and high sensitivity, it can be used for evaluation of telomerase activity in cell extracts for future clinical applications. Furthermore, this design has the ability to be easily integrated into lab-on-chip devices for point-of-care telomerase sensing.
Mahmoudi, Z, Mohammadnejad, J, Razavi Bazaz, S, Abouei Mehrizi, A, Saidijam, M, Dinarvand, R, Ebrahimi Warkiani, M & Soleimani, M 2020, 'Promoted chondrogenesis of hMCSs with controlled release of TGF-β3 via microfluidics synthesized alginate nanogels', Carbohydrate Polymers, vol. 229, pp. 115551-115551.
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The field of cartilage tissue engineering has been evolved in the last decade and a myriad of scaffolding biomaterials and bioactive agents have been proposed. Controlled release of growth factors encapsulated in the polymeric nanomaterials has been of interest notably for the repair of damaged articular cartilage. Here, we proposed an on-chip hydrodynamic flow focusing microfluidic approach for synthesis of alginate nanogels loaded with the transforming growth factor beta 3 (TGF-β3) through an ionic gelation method in order to achieve precise release profile of these bioactive agents during chondrogenic differentiation of mesenchymal stem cells (MSCs). Alginate nanogels with adjustable sizes were synthesized by fine-tuning the flow rate ratio (FRR) in the microfluidic device consisting of cross-junction microchannels. The result of present study showed that the proposed approach can be a promising tool to synthesize bioactive -loaded polymeric nanogels for applications in drug delivery and tissue engineering.
Marsh, DJ, Ma, Y & Dickson, K-A 2020, 'Histone Monoubiquitination in Chromatin Remodelling: Focus on the Histone H2B Interactome and Cancer', Cancers, vol. 12, no. 11, pp. 3462-3462.
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Chromatin remodelling is a major mechanism by which cells control fundamental processes including gene expression, the DNA damage response (DDR) and ensuring the genomic plasticity required by stem cells to enable differentiation. The post-translational modification of histone H2B resulting in addition of a single ubiquitin, in humans at lysine 120 (K120; H2Bub1) and in yeast at K123, has key roles in transcriptional elongation associated with the RNA polymerase II-associated factor 1 complex (PAF1C) and in the DDR. H2Bub1 itself has been described as having tumour suppressive roles and a number of cancer-related proteins and/or complexes are recognised as part of the H2Bub1 interactome. These include the RING finger E3 ubiquitin ligases RNF20, RNF40 and BRCA1, the guardian of the genome p53, the PAF1C member CDC73, subunits of the switch/sucrose non-fermenting (SWI/SNF) chromatin remodelling complex and histone methyltransferase complexes DOT1L and COMPASS, as well as multiple deubiquitinases including USP22 and USP44. While globally depleted in many primary human malignancies, including breast, lung and colorectal cancer, H2Bub1 is selectively enriched at the coding region of certain highly expressed genes, including at p53 target genes in response to DNA damage, functioning to exercise transcriptional control of these loci. This review draws together extensive literature to cement a significant role for H2Bub1 in a range of human malignancies and discusses the interplay between key cancer-related proteins and H2Bub1-associated chromatin remodelling.
Martin, AD, Wojciechowski, JP, Du, EY, Rawal, A, Stefen, H, Au, CG, Hou, L, Cranfield, CG, Fath, T, Ittner, LM & Thordarson, P 2020, 'Decoupling the effects of hydrophilic and hydrophobic moieties at the neuron–nanofibre interface', Chemical Science, vol. 11, no. 5, pp. 1375-1382.
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The mobility of hydrophobic moieties at a peptide nanofibre surface determines its suitability as a scaffold for sensitive primary cells.
McCall, A, Pruna, R, Van der Horst, N, Dupont, G, Buchheit, M, Coutts, AJ, Impellizzeri, FM, Fanchini, M, Azzalin, A, Beck, A, Belli, A, Buchheit, M, Dupont, G, Fanchini, M, Ferrari-Bravo, D, Forsythe, S, Iaia, M, Kugel, Y-B, Martin, I, Melotto, S, Milsom, J, Norman, D, Pons, E, Rapetti, S, Requena, B, Sassi, R, Schlumberger, A, Strudwick, T & Tibaudi, A 2020, 'Exercise-Based Strategies to Prevent Muscle Injury in Male Elite Footballers: An Expert-Led Delphi Survey of 21 Practitioners Belonging to 18 Teams from the Big-5 European Leagues', Sports Medicine, vol. 50, no. 9, pp. 1667-1681.
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Abstract Purpose To define based on expert opinion and practical experience using a systematic and scientific approach, (1) the perceived most effective exercise-based strategies to prevent muscle injury in elite footballers; and, (2) when and how these exercise programs are prescribed based on the number of days between games i.e. implementation strategy. Methods A Delphi survey obtained opinions and assessed for agreement. Delphi respondents consisted of 21 experienced sports practitioners (12 ± 5.3 years in elite football and with an academic background) belonging to 18 teams from the Big-5 European football leagues; England, France, Germany, Italy, Spain. Three teams were represented collaboratively by two experts. The Delphi process involves sequential rounds each evolving based on the responses from the previous. The number of rounds is not pre-defined and continues until an agreement is either achieved or it is clear that no agreement will be reached. Frequency of responses was recorded where the agreement was sought (i.e. in closed questions) and an agreement was achieved if ≥ 13/18 (70%) respondents agreed. For open-ended questions, a qualitative content analysis was performed to identify recurring themes and when themes were specified by ≥ 13 (70%), these were also considered as reaching an agreement. Practitioners had the opportunity to raise concerns if they disagreed with the ‘agreement from recurrent themes’. Results There were four Delphi rounds (100% response for each round). Sprinting and High-Speed Running (HSR) focused exercises were agreed as most effective (perceived) to prevent muscle injuries. Eccentric exercise was ...
McCarthy, MC, De Abreu Lourenco, R, McMillan, LJ, Meshcheriakova, E, Cao, A & Gillam, L 2020, 'Finding Out What Matters in Decision-Making Related to Genomics and Personalized Medicine in Pediatric Oncology: Developing Attributes to Include in a Discrete Choice Experiment', The Patient - Patient-Centered Outcomes Research, vol. 13, no. 3, pp. 347-361.
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ackgroundTreatment decision-making in pediatric oncology can be complex. Recent advances in genome sequencing and novel or ‘personalized’ therapies potentially increases the complexity of decision-making and treatment options.ObjectivesThis study explored the views and experiences of healthcare providers (HCPs) and parents with respect to decision-making in difficult-to-treat cancers, including genomic decision-making.MethodsA two-phase qualitative study was undertaken in which oncologists and nurses and parents of children with relapsed and refractory cancers were interviewed using a semi-structured interview guide. Data were analyzed thematically, with a focus on measurable themes relevant to the development of candidate attributes for a discrete choice experiment (DCE). Secondly, a review of studies that utilized stated preference experiments in the fields of genomics, medical decision-making, and pediatrics was undertaken and compared with the candidate attributes identified from interviews.ResultsSix candidate attributes were developed from the interview themes: clinical benefit, quality of life (QoL) including both treatment effects and functionality, likelihood of a target, cost (who pays), recommendation of HCP or extent family supported the decision, and whether a biopsy was needed. Two further candidate attributes were identified from the literature review: severity of illness and cost (dollar amount).ConclusionsThis study identified eight candidate attributes that will be further validated prior to developing a DCE aimed at better understanding factors influencing decision-making related to genomic sequencing and personalized medicine. This study and the proposed DCE will contribute to improving ethical and clinical practices in the application of novel genomic technology in pediatric oncology.
McCleave, EL, Slattery, KM, Duffield, R, Crowcroft, S, Abbiss, CR, Wallace, LK & Coutts, AJ 2020, 'Concurrent Heat and Intermittent Hypoxic Training: No Additional Performance Benefit Over Temperate Training', International Journal of Sports Physiology and Performance, vol. 15, no. 9, pp. 1260-1271.
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Purpose: To examine whether concurrent heat and intermittent hypoxic training can improve endurance performance and physiological responses relative to independent heat or temperate interval training. Methods: Well-trained male cyclists (N = 29) completed 3 weeks of moderate- to high-intensity interval training (4 × 60 min·wk−1) in 1 of 3 conditions: (1) heat (HOT: 32°C, 50% relative humidity, 20.8% fraction of inspired oxygen, (2) heat + hypoxia (H+H: 32°C, 50% relative humidity, 16.2% fraction of inspired oxygen), or (3) temperate environment (CONT: 22°C, 50% relative humidity, 20.8% fraction of inspired oxygen). Performance 20-km time trials (TTs) were conducted in both temperate (TTtemperate) and assigned condition (TTenvironment) before (base), immediately after (mid), and after a 3-week taper (end). Measures of hemoglobin mass, plasma volume, and blood volume were also assessed. Results: There was improved 20-km TT performance to a similar extent across all groups in both TTtemperate (mean ±90% confidence interval HOT, −2.8% ±1.8%; H+H, −2.0% ±1.5%; CONT, −2.0% ±1.8%) and TTenvironment (HOT, −3.3% ±1.7%; H+H, −3.1% ±1.6%; CONT, −3.2% ±1.1%). Plasma volume (HOT, 3.8% ±4.7%; H+H, 3.3% ±4.7%) and blood volume (HOT, 3.0% ±4.1%; H+H, 4.6% ±3.9%) were both increased at mid in HOT and H+H over CONT. Increased hemoglobin mass was observed in H+H only (3.0% ±1.8%). Conclusion: Three weeks of interval training in heat, concurrent heat and hypoxia, or temperate environments improve 20-km TT performance to the same extent. Despite indications of physiological adaptations, the addition of independent heat or concurrent heat and hypoxia provided no great...
McGowan, EM, Haddadi, N, Nassif, NT & Lin, Y 2020, 'Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19', International Journal of Molecular Sciences, vol. 21, no. 19, pp. 7189-7189.
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The world is currently experiencing the worst health pandemic since the Spanish flu in 1918—the COVID-19 pandemic—caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world’s third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the “cytokine storm syndrome”, endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-appro...
McGrath, KC, Li, X, Twigg, SM & Heather, AK 2020, 'Apolipoprotein-AI mimetic peptides D-4F and L-5F decrease hepatic inflammation and increase insulin sensitivity in C57BL/6 mice', PLOS ONE, vol. 15, no. 1, pp. e0226931-e0226931.
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BACKGROUND:Apolipoprotein-AI (apo-AI) is the major apolipoprotein found in high density lipoprotein particles (HDLs). We previously demonstrated that apo-AI injected directly into high-fat diet fed mice improved insulin sensitivity associated with decreased hepatic inflammation. While our data provides compelling proof of concept, apoA-I mimetic peptides are more clinically feasible. The aim of this study was to test whether apo-AI mimetic peptide (D-4F and L-5F) treatment will emulate the effects of full-length apo-AI to improve insulin sensitivity. METHODS:Male C57BL/6 mice were fed a high-fat diet for 16 weeks before receiving D4F mimetic peptide administered via drinking water or L5F mimetic peptide administered by intraperitoneal injection bi-weekly for a total of five weeks. Glucose tolerance and insulin tolerance tests were conducted to assess the effects of the peptides on insulin resistance. Effects of the peptides on inflammation, gluconeogenic enzymes and lipid synthesis were assessed by real-time PCR of key markers involved in the respective pathways. RESULTS:Treatment with apo-AI mimetic peptides D-4F and L-5F showed: (i) improved blood glucose clearance (D-4F 1.40-fold AUC decrease compared to HFD, P<0.05; L-4F 1.17-fold AUC decrease compared to HFD, ns) in the glucose tolerance test; (ii) improved insulin tolerance (D-4F 1.63-fold AUC decrease compared to HFD, P<0.05; L-5F 1.39-fold AUC compared to HFD, P<0.05) in the insulin tolerance test. The metabolic test results were associated with (i) decreased hepatic inflammation of SAA1, IL-1β IFN-γ and TNFα (2.61-5.97-fold decrease compared to HFD, P<0.05) for both mimetics; (ii) suppression of hepatic mRNA expression of gluconeogenesis-associated genes (PEPCK and G6Pase; 1.66-3.01-fold decrease compared to HFD, P<0.001) for both mimetics; (iii) lipogenic-associated genes, (SREBP1c and ChREBP; 2.15-3.31-fold decrease compared to HFD, P<0.001) for both mimetics and; (iv) reduced hepatic macroph...
Mehmood, A, Zameer, A, Chaudhary, NI, Ling, SH & Raja, MAZ 2020, 'Design of meta-heuristic computing paradigms for Hammerstein identification systems in electrically stimulated muscle models.', Neural Comput. Appl., vol. 32, no. 16, pp. 12469-12497.
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Mihandoust, A, Razavi Bazaz, S, Maleki-Jirsaraei, N, Alizadeh, M, A. Taylor, R & Ebrahimi Warkiani, M 2020, 'High-Throughput Particle Concentration Using Complex Cross-Section Microchannels', Micromachines, vol. 11, no. 4, pp. 440-440.
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High throughput particle/cell concentration is crucial for a wide variety of biomedical, clinical, and environmental applications. In this work, we have proposed a passive spiral microfluidic concentrator with a complex cross-sectional shape, i.e., a combination of rectangle and trapezoid, for high separation efficiency and a confinement ratio less than 0.07. Particle focusing in our microfluidic system was observed in a single, tight focusing line, in which higher particle concentration is possible, as compared with simple rectangular or trapezoidal cross-sections with similar flow area. The sharper focusing stems from the confinement of Dean vortices in the trapezoidal region of the complex cross-section. To quantify this effect, we introduce a new parameter, complex focusing number or CFN, which is indicative of the enhancement of inertial focusing of particles in these channels. Three spiral microchannels with various widths of 400 µm, 500 µm, and 600 µm, with the corresponding CFNs of 4.3, 4.5, and 6, respectively, were used. The device with the total width of 600 µm was shown to have a separation efficiency of ~98%, and by recirculating, the output concentration of the sample was 500 times higher than the initial input. Finally, the investigation of results showed that the magnitude of CFN relies entirely on the microchannel geometry, and it is independent of the overall width of the channel cross-section. We envision that this concept of particle focusing through complex cross-sections will prove useful in paving the way towards more efficient inertial microfluidic devices.
Miller-Lewis, L, Tieman, J, Rawlings, D, Parker, D & Sanderson, C 2020, 'Can Exposure to Online Conversations About Death and Dying Influence Death Competence? An Exploratory Study Within an Australian Massive Open Online Course', OMEGA - Journal of Death and Dying, vol. 81, no. 2, pp. 242-271.
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A Massive Open Online Course, Dying2Learn, was designed to foster community death conversations and strengthen community awareness of palliative care and death as a normal process. This exploratory study used a pre–post prospective design to determine if participation in Dying2Learn and exposure to online conversations about death and dying resulted in any significant influence on death competence in 134 participants who completed the Coping-with-Death-Scale both at the beginning and end of the course in 2016. Death competence refers to a range of attitudes and capabilities people have for dealing with death. Results at the end of the course indicated that engagement in Dying2Learn led to significant improvements in death competence scores over time (medium-to-large effect size). The positive impact was greater for those who completed more of the course, and effectiveness did not depend on sociodemographic characteristics. In conclusion, this study found that an online learning platform in the form of a Massive Open Online Course could engage community members in meaningful social discussion about death and dying, and that exposure to these conversations was beneficial for all participants regardless of previous exposure to death. Further exploration is required to determine whether this change in death competence will have an impact on participant’s behavior in the community regarding death conversations and preparedness.
Mirzaaghaian, A, Ramiar, A, Ranjbar, AA & Warkiani, ME 2020, 'Application of level-set method in simulation of normal and cancer cells deformability within a microfluidic device', Journal of Biomechanics, vol. 112, pp. 110066-110066.
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Application of microfluidic systems for the study of cellular behaviors has been a flourishing area of research in the past decade. In the process of probing cell biomechanics the passage of a cell through a narrow microchannel or a small pore has attracted much attention during the recent years. And the study of cellular deformability and transportability using these systems with enhanced resolution and accuracy has opened a new paradigm for high-throughput characterization of both healthy and diseased cell populations.Here we use the level-set method to explore the relationship between the transit time and mechanical properties of normal white blood cells (WBCs) and breast cancer epithelial cells (MCF7) under different microenvironmental parameters (i.e., pressure difference, cell size, effective cell surface tension, constriction size and taper angle) in a 2-D computational domain by considering the cell as a viscous drop. The novel biomechanical relations are obtained for each cell type by the Response Surface Method (RSM), relating microenvironmental parameters to the dimensionless entry time of the normal and cancer cells. Our results revealed that MCF7 cells show asignificantly different behavior (a bifurcating behavior when the pressure difference of inlet/outlet increases) in regards to the dimensionless entry time as a function of microchannel taper angle in comparison with the WBC. These results suggest that the microenvironmental parameters have a significant effect on the transportability of the cells and different cells have different behaviors in response to a specific microenvironmental parameter. Finally, it can be claimed that this method can be also utilized to distinguish between benign and cancerous cells or even to probe tumor heterogeneity toward high throughput cell cytometry.
Modak, NM, Lobos, V, Merigó, JM, Gabrys, B & Lee, JH 2020, 'Forty years of computers & chemical engineering: A bibliometric analysis', Computers & Chemical Engineering, vol. 141, pp. 106978-106978.
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© 2020 Elsevier Ltd Computers & Chemical Engineering (CCE) is one of the premier international journals in the field of chemical engineering. CCE published its first issue in 1977 and completed forty years in 2016. More than four decades of continuous and successful journey influenced us to celebrate its contribution through a comprehensive bibliometric study. Using the Web of Science Core Collection database we depict trends of the journal in terms of papers, topics, authors, institutions, and countries. Networks visualization of co-citation of journals and authors, bibliographic coupling institutions and countries, and co-occurrence of author keywords are prepared using the visualization of similarities (VOS) viewer software. The present analysis explores publication and citation patterns of the journal. Professor Ignacio E. Grossmann, Carnegie Mellon University, and USA respectively appear as the most productive and influential author, institution, and country in CCE publications. Optimization based research topics received most attention in CCE publications.
Monkman, J, Taheri, T, Ebrahimi Warkiani, M, O’Leary, C, Ladwa, R, Richard, D, O’Byrne, K & Kulasinghe, A 2020, 'High-Plex and High-Throughput Digital Spatial Profiling of Non-Small-Cell Lung Cancer (NSCLC)', Cancers, vol. 12, no. 12, pp. 3551-3551.
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Profiling the tumour microenvironment (TME) has been informative in understanding the underlying tumour–immune interactions. Multiplex immunohistochemistry (mIHC) coupled with molecular barcoding technologies have revealed greater insights into the TME. In this study, we utilised the Nanostring GeoMX Digital Spatial Profiler (DSP) platform to profile a non-small-cell lung cancer (NSCLC) tissue microarray for protein markers across immune cell profiling, immuno-oncology (IO) drug targets, immune activation status, immune cell typing, and pan-tumour protein modules. Regions of interest (ROIs) were selected that described tumour, TME, and normal adjacent tissue (NAT) compartments. Our data revealed that paired analysis (n = 18) of matched patient compartments indicate that the TME was significantly enriched in CD27, CD3, CD4, CD44, CD45, CD45RO, CD68, CD163, and VISTA relative to the tumour. Unmatched analysis indicated that the NAT (n = 19) was significantly enriched in CD34, fibronectin, IDO1, LAG3, ARG1, and PTEN when compared to the TME (n = 32). Univariate Cox proportional hazards indicated that the presence of cells expressing CD3 (hazard ratio (HR): 0.5, p = 0.018), CD34 (HR: 0.53, p = 0.004), and ICOS (HR: 0.6, p = 0.047) in tumour compartments were significantly associated with improved overall survival (OS). We implemented both high-plex and high-throughput methodologies to the discovery of protein biomarkers and molecular phenotypes within biopsy samples, and demonstrate the power of such tools for a new generation of pathology research.
Munday, I, Newton‐John, T & Kneebone, I 2020, '‘Barbed wire wrapped around my feet’: Metaphor use in chronic pain', British Journal of Health Psychology, vol. 25, no. 3, pp. 814-830.
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ObjectivesAs there is no objective test for pain, sufferers rely on language to communicate their pain experience. Pain description frequently takes the form of metaphor; however, there has been limited research in this area. This study thus sought to extend previous findings on metaphor use in specific pain subgroups to a larger, heterogeneous chronic pain sample, utilizing a systematic method of metaphor analysis.DesignConceptual metaphor theory was utilized to explore the metaphors used by those with chronic pain via qualitative methodology.MethodsAn anonymous online survey was conducted which asked for the descriptions and metaphors people use to describe their pain. Systematic metaphor analysis was used to classify and analyse the metaphors used into specific metaphor source domains.ResultsParticipants who reported chronic pain completed the survey (N = 247, age 19–78, M = 43.69). Seven overarching metaphor source domains were found. These were coded as Causes of Physical Damage, Common Pain Experiences, Electricity, Insects, Rigidity, Bodily Misperception, and Death and Mortality.ConclusionsParticipants utilized a wide variety of metaphors to describe their pain. The most common descriptions couched chronic pain in terms of physical damage. A better understanding of pain metaphors may have implications for improved health care communication and provide targets for clinical interventions.
Murphy, C, Deplazes, E, Cranfield, CG & Garcia, A 2020, 'The Role of Structure and Biophysical Properties in the Pleiotropic Effects of Statins', International Journal of Molecular Sciences, vol. 21, no. 22, pp. 8745-8745.
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Statins are a class of drugs used to lower low-density lipoprotein cholesterol and are amongst the most prescribed medications worldwide. Most statins work as a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), but statin intolerance from pleiotropic effects have been proposed to arise from non-specific binding due to poor enzyme-ligand sensitivity. Yet, research into the physicochemical properties of statins, and their interactions with off-target sites, has not progressed much over the past few decades. Here, we present a concise perspective on the role of statins in lowering serum cholesterol levels, and how their reported interactions with phospholipid membranes offer a crucial insight into the mechanism of some of the more commonly observed pleiotropic effects of statin administration. Lipophilicity, which governs hepatoselectivity, is directly related to the molecular structure of statins, which dictates interaction with and transport through membranes. The structure of statins is therefore a clinically important consideration in the treatment of hypercholesterolaemia. This review integrates the recent biophysical studies of statins with the literature on the physiological effects and provides new insights into the mechanistic cause of statin pleiotropy, and prospective means of understanding the cholesterol-independent effects of statins.
Murray-Parahi, P, DiGiacomo, M, Jackson, D, Phillips, J & Davidson, PM 2020, 'Primary health care content in Australian undergraduate nursing curricula', Collegian, vol. 27, no. 3, pp. 271-280.
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Nagy, Z, Cheung, BB, Tsang, W, Tan, O, Herath, M, Ciampa, OC, Shadma, F, Carter, DR & Marshall, GM 2020, 'Withaferin A activates TRIM16 for its anti-cancer activity in melanoma', Scientific Reports, vol. 10, no. 1.
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AbstractAlthough selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease.
Naji, M, Braytee, A, Al-Ani, A, Anaissi, A, Goyal, M & Kennedy, PJ 2020, 'Design of airport security screening using queueing theory augmented with particle swarm optimisation', Service Oriented Computing and Applications, vol. 14, no. 2, pp. 119-133.
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© 2020, Springer-Verlag London Ltd., part of Springer Nature. Designing an efficient and reliable airport security screening system is a critical and challenging task. It is an essential element of airline and passenger safety which aims to provide the expected level of confidence and to ensure the safety of passengers and the aviation industry. In recent years, security at airports has gone through noticeable improvements with the utilisation of advanced technology and highly trained security officers. However, for many airports, it is important to find the best compromise between the capacity of the security area, the number of passengers and the number of screening machines and officers to maintain a high level of security and to ensure that the cost and waiting times for passengers and airlines are at acceptable levels. This paper proposes a novel method based on queueing theory augmented with particle swarm optimisation (QT-PSO) to predict passenger waiting times in a security screening context. This model consists of multiple servers operating in parallel and takes into consideration the complete scenario such as normal, slow and express lanes. Such an approach has the potential to be a reliable model that is able to assimilate variations in the number of passengers, security officers and security machines on the service time. To evaluate our proposed method, we collected real-world security screening data from an Australian airport from December to March for the two consecutive years of 2016 and 2017. The results show that our proposed QT-PSO method is superior to predict the average waiting time of passengers compared to the state of the art.
Ngo, CQ, Chai, R, Nguyen, TV, Jones, TW & Nguyen, HT 2020, 'Electroencephalogram Spectral Moments for the Detection of Nocturnal Hypoglycemia', IEEE Journal of Biomedical and Health Informatics, vol. 24, no. 5, pp. 1237-1245.
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Hypoglycemia or low blood glucose is the most feared complication of insulin treatment of diabetes. For people with diabetes, the mismatch between the insulin therapy and the body's physiology could increase the risk of hypoglycemia. Nocturnal hypoglycemia is particularly dangerous for type-1 diabetes patients because its symptoms may obscure during sleep. The early onset detection of hypoglycemia at night time is necessary because it can result in unconsciousness and even death. This paper presents new electroencephalogram spectral features for nocturnal hypoglycemia detection. The system uses high-order spectral moments for feature extraction and Bayesian neural network for classification. From a clinical study of hypoglycemia of eight patients with type-1 diabetes at night, we find that these spectral moments of theta band and alpha band changed significantly. During hypoglycemia episodes, the theta moments increased significantly (P < 0.001) while the features of alpha band reduced significantly (P < 0.001). Using the optimal Bayesian neural network, the classification results were 85% and 52% in sensitivity and specificity, respectively. The significant correlation (P < 0.001) with real blood glucose profiles shows the effectiveness of the proposed features for the detection of nocturnal hypoglycemia.
Nguyen, HG & Nguyen, TV 2020, 'An epidemiologic profile of COVID-19 patients in Vietnam'.
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AbstractBackground and AimThere is a paucity of data on the COVID-19 pandemic in Vietnam. In this paper, we sought to provide an epidemiologic description of patients who were infected with SARS-Cov-2 in Vietnam.MethodsData were abstracted from the wikipedia’s COVID-19 information resource and Johns Hopkins University Dashboard. Demographic data and treatment status were obtained for each patient in each day. The coverage period was from 23/1/2020 to 10/4/2020. Descriptive analyses of incident cases were stratified by gender and age group. The estimation of the reproduction ratio was done with a bootstrap method using the R statistical environment.ResultsDuring the coverage period, Vietnam has recorded 257 cases of COVID-19. Approximately 54% of the cases were women. The median age of patients was 30 years (range: 3 months to 88 years), with 78% of patients aged 49 or younger. About 66% (n = 171) of patients were overseas tourists (20%) and Vietnamese students or workers returning from overseas (46%). Approximately 57% (n = 144) of patients have been recovered and discharged from hospitals. There have been no mortality. The reproduction ratio was estimated to range between 0.95 and 1.24.ConclusionThese data indicate that a majority of COVID-19 patients in Vietnam was imported cases in overseas tourists and young students and workers who had returned from overseas.
Nguyen, HG, Pham, MTD, Ho-Pham, LT & Nguyen, TV 2020, 'Lean mass and peak bone mineral density', Osteoporosis and Sarcopenia, vol. 6, no. 4, pp. 212-216.
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Nguyen, L & Miro, JV 2020, 'An Efficient 3-D Model for Remaining Wall Thicknesses of Cast Iron Pipes in Nondestructive Testing', IEEE Sensors Letters, vol. 4, no. 7, pp. 1-4.
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© 2017 IEEE. Over 50% of global pipes have been made of cast iron, and most of them are aging. In order to effectively estimate possibilities of their failures, which is paramount for efficiently managing asset infrastructures, it requires the remaining wall thickness (RWT) of a pipe to be known. In fact, RWT of the cast iron pipes can be primarily measured by the magnetism based nondestructive testing technologies though they are quite slow. To speed up the inspection process, it is proposed to sense RWT of a part of a pipe and then employ a model to predict RWT in the rest. Thus, this letter introduces a 3-D model to efficiently represent RWT of a pipe given measurements collected intermittently on the pipe's surface. The proposed model first transforms 3-D cylindrical coordinates to 3-D Cartesian coordinates before modeling RWT by Gaussian processes (GP). The transformation allows GP to work properly on RWT data gathered on a cylindrical pipe and effectively predict RWT at unmeasured locations. Moreover, periodicity of RWT along circumference of the pipe is naturally integrated. The effectiveness of the proposed approach is demonstrated by implementation in two real life inservice aging cast iron pipes, where the obtained results are highly promising.
Nguyen, L & Miro, JV 2020, 'An Efficient 3-D Model for Remaining Wall Thicknesses of Cast Iron Pipes in Nondestructive Testing', IEEE Sensors Letters, vol. 4, no. 7.
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© 2017 IEEE. Over 50% of global pipes have been made of cast iron, and most of them are aging. In order to effectively estimate possibilities of their failures, which is paramount for efficiently managing asset infrastructures, it requires the remaining wall thickness (RWT) of a pipe to be known. In fact, RWT of the cast iron pipes can be primarily measured by the magnetism based nondestructive testing technologies though they are quite slow. To speed up the inspection process, it is proposed to sense RWT of a part of a pipe and then employ a model to predict RWT in the rest. Thus, this letter introduces a 3-D model to efficiently represent RWT of a pipe given measurements collected intermittently on the pipe's surface. The proposed model first transforms 3-D cylindrical coordinates to 3-D Cartesian coordinates before modeling RWT by Gaussian processes (GP). The transformation allows GP to work properly on RWT data gathered on a cylindrical pipe and effectively predict RWT at unmeasured locations. Moreover, periodicity of RWT along circumference of the pipe is naturally integrated. The effectiveness of the proposed approach is demonstrated by implementation in two real life inservice aging cast iron pipes, where the obtained results are highly promising.
Nguyen, L & Miro, JV 2020, 'Efficient Evaluation of Remaining Wall Thickness in Corroded Water Pipes Using Pulsed Eddy Current Data', IEEE Sensors Journal, vol. 20, no. 23, pp. 14465-14473.
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© 2001-2012 IEEE. In order to analyse failures of an ageing water pipe, some methods such as the loss-of-section require remaining wall thickness (RWT) along the pipe to be fully known, which can be measured by the magnetism based non-destructive evaluation sensors though they are practically slow due to the magnetic penetrating process. That is, fully measuring RWT at every location in a water pipe is not really practical if RWT inspection causes disruption of water supply to customers. Thus, this paper proposes a new data prediction approach that can increase amount of RWT data of a corroded water pipe collected in a given period of time by only measuring RWT on a part (e.g. 20%) of the total pipe surface area and then employing the measurements to predict RWT at unmeasured area. It is proposed to utilize a marginal distribution to convert the non-Gaussian RWT measurements to the standard normally distributed data, which can then be input into a 3-dimensional Gaussian process model for efficiently predicting RWT at unmeasured locations on the pipe. The proposed approach was implemented in two real-life in-service pipes, and the obtained results demonstrate its practicality.
Nguyen, LT, Saad, S, Chen, H & Pollock, CA 2020, 'Parental SIRT1 Overexpression Attenuate Metabolic Disorders Due to Maternal High-Fat Feeding', International Journal of Molecular Sciences, vol. 21, no. 19, pp. 7342-7342.
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Maternal obesity can contribute to the development of obesity and related metabolic disorders in progeny. Sirtuin (SIRT)1, an essential regulator of metabolism and stress responses, has recently emerged as an important modifying factor of developmental programming. In this study, to elucidate the effects of parental SIRT1 overexpression on offspring mechanism, four experimental groups were included: (1) Chow-fed wild-type (WT)-dam × Chow-fed WT-sire; (2) High-fat diet (HFD)-fed WT-dam × Chow-fed WT-sire; (3) HFD-fed hemizygous SIRT1-transgenic (Tg)-dam × Chow-fed WT-sire; and (4) HFD-fed WT dam × Chow-fed Tg-sire. Our results indicate that Tg breeders had lower body weight and fat mass compared to WT counterparts and gave birth to WT offspring with reductions in body weight, adiposity and hyperlipidaemia compared to those born of WT parents. Maternal SIRT1 overexpression also reversed glucose intolerance, and normalised abnormal fat morphology and the expression of dysregulated lipid metabolism markers, including SIRT1. Despite having persistent hepatic steatosis, offspring born to Tg parents showed an improved balance of hepatic glucose/lipid metabolic markers, as well as reduced levels of inflammatory markers and TGF-β/Smad3 fibrotic signalling. Collectively, the data suggest that parental SIRT1 overexpression can ameliorate adverse metabolic programming effects by maternal obesity.
Nguyen, TV 2020, 'Common methodological issues and suggested solutions in bone research', Osteoporosis and Sarcopenia, vol. 6, no. 4, pp. 161-167.
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Bone research is a dynamic area of scientific investigation that usually encompasses multidisciplines. Virtually all basic cellular research, clinical research and epidemiologic research rely on statistical concepts and methodology for inference. This paper discusses common issues and suggested solutions concerning the application of statistical thinking in bone research, particularly in clinical and epidemiological investigations. The issues are sample size estimation, biases and confounders, analysis of longitudinal data, categorization of continuous data, selection of significant variables, over-fitting, P-values, false positive finding, confidence interval, and Bayesian inference. It is hoped that by adopting the suggested measures the scientific quality of bone research can improve.
Nguyen, TV 2020, 'Toward the era of precision fracture risk assessment', The Journal of Clinical Endocrinology & Metabolism, vol. 105, no. 7, pp. e2636-e2638.
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Nguyen, TV & Eisman, JA 2020, 'Post‐GWAS Polygenic Risk Score: Utility and Challenges', JBMR Plus, vol. 4, no. 11, p. e10411.
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ABSTRACTOver the past decade, through genome‐wide association studies, more than 300 genetic variants have been identified to be associated with either BMD or fracture risk. These genetic variants are common in the general population, but they exert small to modest effects on BMD, suggesting that the utility of any single variant is limited. However, a combination of effect sizes from multiple variants in the form of the polygenic risk score (PRS) can provide a useful indicator of fracture risk beyond that obtained by conventional clinical risk factors. In this perspective, we review the progress of genetics of osteoporosis and approaches for creating PRSs, their uses, and caveats. Recent studies support the idea that the PRS, when integrated into existing fracture prediction models, can help clinicians and patients alike to better assess the fracture risk for an individual, and raise the possibility of precision risk assessment. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Nikoloska, R, Bykerk, L, Vitanage, D, Valls Miro, J, Chen, F, Wang, Y & Liang, B 2020, 'Enhancing Sydney Water’s leak prevention through acoustic monitoring', Water e-Journal, vol. 5, no. 2, pp. 1-15.
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Okusogu, C, Wang, Y, Akintola, T, Haycock, NR, Raghuraman, N, Greenspan, JD, Phillips, J, Dorsey, SG, Campbell, CM & Colloca, L 2020, 'Placebo hypoalgesia: racial differences', Pain, vol. 161, no. 8, pp. 1872-1883.
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Abstract No large-cohort studies that examine potential racial effects on placebo hypoalgesic effects exist. To fill this void, we studied placebo effects in healthy and chronic pain participants self-identified as either African American/black (AA/black) or white. We enrolled 372 study participants, 186 with a diagnosis of temporomandibular disorder (TMD) and 186 race-, sex-, and age-matched healthy participants to participate in a placebo experiment. Using a well-established paradigm of classical conditioning with verbal suggestions, each individual pain sensitivity was measured to calibrate the temperatures for high- and low-pain stimuli in the conditioning protocol. These 2 temperatures were then paired with a red and green screen, respectively, and participants were told that the analgesic intervention would activate during the green screens to reduce pain. Participants then rated the painfulness of each stimulus on a visual analog scale ranging from 0 to 100. Racial influences were tested on conditioning strength, reinforced expectations, and placebo hypoalgesia. We found that white participants reported greater conditioning effects, reinforced relief expectations, and placebo effects when compared with their AA/black counterparts. Racial effects on placebo were observed in TMD, although negligible, short-lasting, and mediated by conditioning strength. Secondary analyses on the effect of experimenter-participant race and sex concordance indicated that same experimenter-participant race induced greater placebo hypoalgesia in TMDs while different sex induced greater placebo hypoalgesia in healthy participants. This is the first and largest study to analyze racial effects on placebo hypoalgesia and has implications for both clinical research and treatment outcomes.
Oliveira Borges, T, Bullock, N, Aitken, D, Cox, GR & Coutts, AJ 2020, 'Metabolic Cost of Paddling on Different Commercially Available Kayak Ergometers', International Journal of Sports Physiology and Performance, vol. 15, no. 8, pp. 1189-1192.
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Purpose: To compare the metabolic cost of paddling on different commercially available kayak ergometers using a standardized kayak incremental exercise protocol. Methods: Six male sprint kayak athletes undertook an incremental exercise protocol on 3 different kayak ergometers utilizing a randomized counterbalanced pair-matched design. Results: Mean maximal aerobic power on the WEBA ergometer (265 [14] W) was significantly higher than on the Dansprint (238 [9] W) and KayakPro® (247 [21] W, P < .01, effect size [ES] = 0.80). At the fifth stage, absolute oxygen consumption on the WEBA (3.82 [0.25] L·min−1) was significantly lower (P < 0.05, ES = 0.20) than KayakPro and Dansprint (4.10 [0.28] and 4.08 [0.27] L·min−1, respectively). Blood lactate concentration response at the sixth stage was significantly lower for the WEBA (3.5 [0.8] mmol·L−1), compared with KayakPro and Dansprint (5.4 [1.2] and 5.6 [1.5] mmol·L−1, P = .012, ES = 0.20). Stroke rate was significantly higher, without any effect of pacing during the submaximal stages for the Dansprint, compared with the WEBA (P < .001, ES = 0.28) and KayakPro (P < .001, ES = 0.38). A pacing effect was present at the maximal stage for all ergometers. Conclusions: This study demonstrated that paddling on different kayak ergometers when controlling power output elicits different metabolic and work outputs. It is recommended that scientists and coaches avoid testing on different ergometers and regularly calibrate these devices. Moreover, when an ergometer has bee...
Ong, JJ, De Abreu Lourenco, R, Street, D, Smith, K, Jamil, MS, Terris-Prestholt, F, Fairley, CK, McNulty, A, Hynes, A, Johnson, K, Chow, EPF, Bavinton, B, Grulich, A, Stoove, M, Holt, M, Kaldor, J & Guy, R 2020, 'The Preferred Qualities of Human Immunodeficiency Virus Testing and Self-Testing Among Men Who Have Sex With Men: A Discrete Choice Experiment', Value in Health, vol. 23, no. 7, pp. 870-879.
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Pandian, V, Morris, LL, Brodsky, MB, Lynch, J, Walsh, B, Rushton, C, Phillips, J, Rahman, A, DeRose, T, Lambe, L, Lami, L, Wu, SPM, Garza, FP, Maiani, S, Zavalis, A, Okusanya, KA, Palmieri, PA, McGrath, BA, Pelosi, P, Sole, ML, Davidson, P & Brenner, MJ 2020, 'Critical Care Guidance for Tracheostomy Care During the COVID-19 Pandemic: A Global, Multidisciplinary Approach', American Journal of Critical Care, vol. 29, no. 6, pp. e116-e127.
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Purpose Critical care nurses caring for patients with a tracheostomy are at high risk because of the predilection of SARS-CoV-2 for respiratory and mucosal surfaces. This review identifies patient-centered practices that ensure safety and reduce risk of infection transmission to health care workers during the coronavirus disease 2019 (COVID-19) pandemic. Methods Consensus statements, guidelines, institutional recommendations, and scientific literature on COVID-19 and previous outbreaks were reviewed. A global interdisciplinary team analyzed and prioritized findings via electronic communications and video conferences to develop consensus recommendations. Results Aerosol-generating procedures are commonly performed by nurses and other health care workers, most notably during suctioning, tracheostomy tube changes, and stoma care. Patient repositioning, readjusting circuits, administering nebulized medications, and patient transport also present risks. Standard personal protective equipment includes an N95/FFP3 mask with or without surgical masks, gloves, goggles, and gown when performing aerosol-generating procedures for patients with known or suspected COVID-19. Viral testing of bronchial aspirate via tracheostomy may inform care providers when determining the protective equipment required. The need for protocols to reduce risk of transmission of infection to nurses and other health care workers is evident. Conclusion Critical care nurses and multidisciplinary teams often care for patients w...
Parker, KJ, Hickman, LD, Phillips, JL & Ferguson, C 2020, 'Interventions to optimise transitional care coordination for older people living with dementia and concomitant multimorbidity and their caregivers: A systematic review', Contemporary Nurse, vol. 56, no. 5-6, pp. 505-533.
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Background: People living with dementia and multimorbidity are frequent uses of health, amplifying risk of fragmented care when moving between care settings.Objectives: This Systematic review aims to identify interventions to support transitional care for older people living with dementia and multimorbidity, and their caregivers.Methods: A systematic search from January 2000-2018 of academic databases for studies which implemented a transitional care intervention for older people living with dementia and multimorbidity, and their caregivers.Results: Out of 6053 identified citations, 11 studies and 13 papers were included. These studies included 1861 people living with dementia, mean age 80 years and 1503 caregivers, mean age of 69 years. Narrative synthesis identifed six elements of care that optimise outcomes; unmet needs; depression; education and support; physical decline; poor quality of life and; access and knowledge of community services.Conclusion: This review demonstrates the paucity of interventions available to reduce impact and experiences of transitions for this vulnerable population. The need is increasing for further research and development in transitional care.
Pazderka, CW, Oliver, B, Murray, M & Rawling, T 2020, 'Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and their Application in Drug Discovery', Current Medicinal Chemistry, vol. 27, no. 10, pp. 1670-1689.
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Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play crucial and often opposing regulatory roles in health and in pathological conditions. n-3 and n-6 PUFA undergo biotransformation to parallel series of lipid mediators that are potent modulators of many cellular processes. A wide range of biological actions have been attributed to lipid mediators derived from n-6 PUFA, and these mediators have served as lead compounds in the development of numerous clinically approved drugs, including latanoprost (Xalatan: Pfizer), which is listed on the WHO Model List of Essential Medicines. n-3 PUFA-derived mediators have received less attention, in part because early studies suggested that n-3 PUFA act simply as competitive substrates for biotransformation enzymes and decrease the formation of n-6 PUFA-derived lipid mediators. However, more recent studies suggest that n-3 PUFA-derived mediators are biologically important in their own right. It is now emerging that many n-3 PUFA-derived lipid mediators have potent and diverse activities that are distinct from their n-6 counterparts. These findings provide new opportunities for drug discovery. Herein, we review the biosynthesis of n-3 PUFA-derived lipid mediators and highlight their biological actions that may be exploited for drug development. Lastly, we provide examples of medicinal chemistry research that has utilized n-3 PUFA-derived lipid mediators as novel lead compounds in drug design.
Pham, M, Hoang, DB & Chaczko, Z 2020, 'Congestion-Aware and Energy-Aware Virtual Network Embedding', IEEE/ACM Transactions on Networking, vol. 28, no. 1, pp. 210-223.
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Phillips, J, Johnston, B & McIlfatrick, S 2020, 'Valuing palliative care nursing and extending the reach', Palliative Medicine, vol. 34, no. 2, pp. 157-159.
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Pluss, M, Novak, A, Bennett, K, Panchuk, D, Coutts, A & Fransen, J 2020, 'Perceptual-motor Abilities Underlying Expertise in Esports', Journal of Expertise, vol. 3, no. 2, pp. 133-143.
Poon, C, Chou, J, Cortie, M & Kabakova, I 2020, 'Brillouin imaging for studies of micromechanics in biology and biomedicine: from current state-of-the-art to future clinical translation', Journal of Physics: Photonics, vol. 3, no. 1, pp. 1-25.
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Brillouin imaging is increasingly recognized to be a powerful technique thatenables non-invasive measurement of the mechanical properties of cells andtissues on a microscopic scale. This provides an unprecedented tool forinvestigating cell mechanobiology, cell-matrix interactions, tissuebiomechanics in healthy and disease conditions and other fundamental biologicalquestions. Recent advances in optical hardware have particularly acceleratedthe development of the technique, with increasingly finer spectral resolutionand more powerful system capabilities. We envision that further developmentswill enable translation of Brillouin imaging to assess clinical specimens andsamples for disease screening and monitoring. The purpose of this review is tosummarize the state-of-the-art in Brillouin microscopy and imaging with aspecific focus on biological tissue and cell measurements. Key system andoperational requirements will be discussed to facilitate wider application ofBrillouin imaging along with current challenges for translation of thetechnology for clinical and medical applications.
Qian, K, Liu, H, Valls Miro, J, Jing, X & Zhou, B 2020, 'Hierarchical and parameterized learning of pick-and-place manipulation from under-specified human demonstrations', Advanced Robotics, vol. 34, no. 13, pp. 858-872.
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© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group and The Robotics Society of Japan. Imitating manipulation skills through observing human demonstrations in everyday life is promising in allowing service robots to be programed quickly, as well as to perform human-like behaviors. Such a Learning by demonstration (LbD) problem is challenging because robots are expected to adapt their learned behaviors to the changes of task parameters and the environment, rather than simply cloning the human teacher's motion. In this paper, we propose a hierarchical and parameterized LbD framework that combines symbolic and trajectory learning of pick-and-place manipulation tasks. We have extended the two-step parameterized learning method with error compensation for learning Environment-adaptive Action Primitives (EaAPs), which is capable of adapting robot's reproduced trajectories to new task instances as well as environmental changes. To arrive at refined plans in situations of under-specified human demonstrations, we propose to model the semantics of demonstrated activities with PDDL-based skill scripts. Therefore, latent motion primitives that are impossible to be learned directly from observing human demonstration in noisy video data can be inferred. The proposed method is implemented as a hierarchical LbD framework and has been evaluated on real robot hardware to illustrate the effectiveness of the proposed approach.
Qu, X & Donnelly, R 2020, 'Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome', International Journal of Molecular Sciences, vol. 21, no. 21, pp. 8191-8191.
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Human sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver that binds sex steroids with high affinity and specificity. Clinical observations and reports in the literature have suggested a negative correlation between circulating SHBG levels and markers of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Decreased SHBG levels increase the bioavailability of androgens, which in turn leads to progression of ovarian pathology, anovulation and the phenotypic characteristics of polycystic ovarian syndrome (PCOS). This review will use a case report to illustrate the inter-relationships between SHBG, NAFLD and PCOS. In particular, we will review the evidence that low hepatic SHBG production may be a key step in the pathogenesis of PCOS. Furthermore, there is emerging evidence that serum SHBG levels may be useful as a diagnostic biomarker and therapeutic target for managing women with PCOS.
Ramakrishna, VAS, Chamoli, U, Rajan, G, Mukhopadhyay, SC, Prusty, BG & Diwan, AD 2020, 'Smart orthopaedic implants: A targeted approach for continuous postoperative evaluation in the spine', Journal of Biomechanics, vol. 104, pp. 109690-109690.
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Rao, A, Zecchin, R, Newton, PJ, Phillips, JL, DiGiacomo, M, Denniss, AR & Hickman, LD 2020, 'The prevalence and impact of depression and anxiety in cardiac rehabilitation: A longitudinal cohort study', European Journal of Preventive Cardiology, vol. 27, no. 5, pp. 478-489.
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Background Co-morbid depression and anxiety symptoms are frequently under-recognised and under-treated in heart disease and this negatively impacts self-management. Aims The purpose of this study was to determine the prevalence, correlates and predictors of depression and anxiety in cardiac rehabilitation programmes, the impact of cardiac rehabilitation on moderate depression, anxiety and stress symptoms, and the relationship between moderate depression, anxiety and stress symptoms and cardiac rehabilitation adherence. Methods This was a retrospective cohort study of 5908 patients entering cardiac rehabilitation programmes from 2006–2017, across two Sydney metropolitan teaching hospitals. Variables included demographics, diagnoses, cardiovascular risk factors, medication use, participation rates, health status (Medical Outcomes Study Short Form-36) and psychological health (Depression Anxiety Stress Scales) subscale scores. Results Moderate depression, anxiety or stress symptoms were prevalent in 18%, 28% and 13% of adults entering cardiac rehabilitation programmes, respectively. Adults with moderate depression (24% vs 13%), anxiety (32% vs 23%) or stress (18% vs 10%) symptoms were significantly less likely to adhere to cardiac rehabilitation compared with those with normal-mild symptoms ( p < 0.001). Anxiety (odds ratio 4.395, 95% confidence interval 3.363–5.744, p < 0.001) and stress (odds ratio 4.527, 95% confidence interval 3.315–6.181, p < 0.001) were the strongest predictors of depression. Depression (odds ratio 3.167, 95% confidence interval 2.411–4.161) and stress (odds ratio 5.577, 95% confidence interval 4.006–7.765, p < 0.001) increased the risk of anxiety on entry by more than three times, above socio-...
Raoufi, MA, Razavi Bazaz, S, Niazmand, H, Rouhi, O, Asadnia, M, Razmjou, A & Ebrahimi Warkiani, M 2020, 'Fabrication of unconventional inertial microfluidic channels using wax 3D printing', Soft Matter, vol. 16, no. 10, pp. 2448-2459.
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A novel workflow for the fabrication of inertial microfluidic devices based on the wax 3D printing method.
Rathnayake, SNH, Hoesein, FAAM, Galban, CJ, ten Hacken, NHT, Oliver, BGG, van den Berge, M & Faiz, A 2020, 'Gene expression profiling of bronchial brushes is associated with the level of emphysema measured by computed tomography-based parametric response mapping', American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 318, no. 6, pp. L1222-L1228.
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Parametric response mapping (PRM) is a computed tomography (CT)-based method to phenotype patients with chronic obstructive pulmonary disease (COPD). It is capable of differentiating emphysema-related air trapping with nonemphysematous air trapping (small airway disease), which helps to identify the extent and localization of the disease. Most studies evaluating the gene expression in smokers and COPD patients related this to spirometric measurements, but none have investigated the relationship with CT-based measurements of lung structure. The current study aimed to examine gene expression profiles of brushed bronchial epithelial cells in association with the PRM-defined CT-based measurements of emphysema (PRMEmph) and small airway disease (PRMfSAD). Using the Top Institute Pharma (TIP) study cohort (COPD = 12 and asymptomatic smokers = 32), we identified a gene expression signature of bronchial brushings, which was associated with PRMEmph in the lungs. One hundred thirty-three genes were identified to be associated with PRMEmph. Among the most significantly associated genes, CXCL11 is a potent chemokine involved with CD8+ T cell activation during inflammation in COPD, indicating that it may play an essential role in the development of emphysema. The PRMEmph signature was then replicated in two independent data sets. Pathway analysis showed that the PRMEmph signature is associated with proinflammatory and notch signaling pathways. Together these findings indicate that airway epithelium may play a role in the development of emphysema and/or may act as a biomarker for the presence of emphysema. In contrast, its role in relation to functional small airways disease is less clear.
Rawling, T, MacDermott-Opeskin, H, Roseblade, A, Pazderka, C, Clarke, C, Bourget, K, Wu, X, Lewis, W, Noble, B, Gale, PA, O'Mara, ML, Cranfield, C & Murray, M 2020, 'Aryl urea substituted fatty acids: a new class of protonophoric mitochondrial uncoupler that utilises a synthetic anion transporter', Chemical Science, vol. 11, no. 47, pp. 12677-12685.
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A new mitochondrial uncoupler that forms membrane permeable dimers through interactions of remote acidic and anion receptor groups.
Razavi Bazaz, S, Amiri, HA, Vasilescu, S, Abouei Mehrizi, A, Jin, D, Miansari, M & Ebrahimi Warkiani, M 2020, 'Obstacle-free planar hybrid micromixer with low pressure drop', Microfluidics and Nanofluidics, vol. 24, no. 8.
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© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Planar micromixers with repetitive units have received substantial research interest since they allow low cost, lab-on-a-chip (LOC), and point-of-care (POC) systems to achieve a proper level of mixing for any given process. This paper presents an efficient planar micromixer that combines four types of mixing units, including convergent–divergent, circular, rhombic, and G-shaped micromixers. Their combinations and resulting effects on the mixing efficiency are numerically and experimentally investigated. A comprehensive Taguchi design of experiment method was used to reduce the number of the combinations from 1024 to only 16, among which a micromixer made of rhombic and G-shaped units readily showed a mixing efficiency beyond 80% over a wide range of inlet Reynolds numbers 0.001–0.3 and 35–65; meanwhile, a pressure drop as low as 12 kPa was reported. The velocity and concentration fields and their gradients within the nominated micromixer were analyzed, providing a better understanding of the mixing mechanism. These results offer design insights for further development of planar micromixers with repetitive unites for low-cost LOC and POC devices.
Razavi Bazaz, S, Hazeri, AH, Rouhi, O, Mehrizi, AA, Jin, D & Warkiani, ME 2020, 'Volume-preserving strategies to improve the mixing efficiency of serpentine micromixers', Journal of Micromechanics and Microengineering, vol. 30, no. 11, pp. 115022-115022.
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Abstract In this study, we have proposed volume-preserving strategies to boost chaoticadvection and improve the mixing efficiency of serpentine micromixers. The proposed strategies revolve around the point that the volume of the micromixer is kept constant during the manipulation. The first strategy involves the utilization of a nozzle-diffuser (ND) shaped microchannel. Using this, the velocity of the fluids fluctuates in an alternating pattern, leading to additional chaotic advection, a decrease in the mixing path, and an increase in the mixing index. The second strategy uses non-aligned inlets to generate swirl inducing effects at the microchannel entrance, where the collision of two fluids generates angular momentum in the flow, providing more chaotic advection. These strategies proved to be effective in boosting the mixing efficiency over wide ranges of Re in which 60% enhancement (from 20.53% to 80.31%) was achieved for Re of 30 by applying an ND shaped microchannel, and 20% enhancement (from 12.71% to 32.21%) was achieved for a critical Re of 15 by applying both of the strategies simultaneously.
Razavi Bazaz, S, Mashhadian, A, Ehsani, A, Saha, SC, Krüger, T & Ebrahimi Warkiani, M 2020, 'Computational inertial microfluidics: a review', Lab on a Chip, vol. 20, no. 6, pp. 1023-1048.
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Schematic illustration of various kinds of geometries used for inertial microfluidics.
Razavi Bazaz, S, Rouhi, O, Raoufi, MA, Ejeian, F, Asadnia, M, Jin, D & Ebrahimi Warkiani, M 2020, '3D Printing of Inertial Microfluidic Devices', Scientific Reports, vol. 10, no. 1, p. 5929.
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AbstractInertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale man...
Reddy, KD, Rutting, S, Tonga, K, Xenaki, D, Simpson, JL, McDonald, VM, Plit, M, Malouf, M, Zakarya, R & Oliver, BG 2020, 'Sexually dimorphic production of interleukin‐6 in respiratory disease', Physiological Reports, vol. 8, no. 11.
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Diverging susceptibility and severity in respiratory diseases is prevalent between males and females. Sex hormones have inconclusively been attributed as the cause of these differences, however, strong evidence exists promoting genetic factors leading to sexual dimorphism. As such, we investigate differential proinflammatory cytokine (interleukin (IL)-6 and CXCL8) release from TNF-α stimulated primary human lung fibroblasts in vitro. We present, for the first time, in vitro evidence supporting clinical findings of differential production of IL-6 between males and females across various respiratory diseases. IL-6 was found to be produced approximately two times more from fibroblasts derived from females compared to males. As such we demonstrate sexual dimorphism in cytokine production of IL-6 outside the context of biological factors in the human body. As such, our data highlight that differences exist between males and females in the absence of sex hormones. We, for the first time, demonstrate inherent in vitro differences exist between males and females in pulmonary fibroblasts.
Reza, AM, Tavakoli, J, Zhou, Y, Qin, J & Tang, Y 2020, 'Synthetic fluorescent probes to apprehend calcium signalling in lipid droplet accumulation in microalgae—an updated review', Science China Chemistry, vol. 63, no. 3, pp. 308-324.
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Rezaei, M, Razavi Bazaz, S, Zhand, S, Sayyadi, N, Jin, D, Stewart, MP & Ebrahimi Warkiani, M 2020, 'Point of Care Diagnostics in the Age of COVID-19', Diagnostics, vol. 11, no. 1, pp. 9-9.
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The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated serious respiratory disease, coronavirus disease 2019 (COVID-19), poses a major threat to global public health. Owing to the lack of vaccine and effective treatments, many countries have been overwhelmed with an exponential spread of the virus and surge in the number of confirmed COVID-19 cases. Current standard diagnostic methods are inadequate for widespread testing as they suffer from prolonged turn-around times (>12 h) and mostly rely on high-biosafety-level laboratories and well-trained technicians. Point-of-care (POC) tests have the potential to vastly improve healthcare in several ways, ranging from enabling earlier detection and easier monitoring of disease to reaching remote populations. In recent years, the field of POC diagnostics has improved markedly with the advent of micro- and nanotechnologies. Due to the COVID-19 pandemic, POC technologies have been rapidly innovated to address key limitations faced in existing standard diagnostic methods. This review summarizes and compares the latest available POC immunoassay, nucleic acid-based and clustered regularly interspaced short palindromic repeats- (CRISPR)-mediated tests for SARS-CoV-2 detection that we anticipate aiding healthcare facilities to control virus infection and prevent subsequent spread.
Rezaeian, M, Georgevsky, D, Golzan, SM, Graham, S, Avolio, A & Butlin, M 2020, 'Pressure Dependency of Retinal Arterial Pulse Wave Velocity in the Rat', Artery Research, vol. 26, no. 1, pp. 27-33.
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Abstract Purpose The retinal vasculature provides unique in vivo access to the microcirculation and presents the possibility of measuring small artery (retinal) stiffness using pulse wave velocity (PWV). This study investigates whether retinal artery PWV (rPWV) has a blood pressure (BP) dependency. Methods Fundus videos from eight Sprague-Dawley rats aged 12 weeks were captured (Zeiss fundus microscope with high-speed camera, 125 fps, Optronis, Germany) simultaneously with aortic BP. Retinal artery diameter waveforms at proximal and distal sites were extracted and transit time calculated from the phase delay between frequency components (4–6 Hz, typical heart rate of rats) of the waveforms. rPWV was measured across a physiological range of mean arterial pressure (MAP): baseline (90–110 mmHg); 130 mmHg to baseline following systemic phenylephrine (PE) infusion (30 µg/kg/min); 130 mmHg to baseline during PE infusion with simultaneous inferior vena cava occlusion (VO); 70 mmHg to baseline following systemic sodium nitroprusside infusion; and 70 mmHg to baseline following VO. The correlation between retinal artery rPWV and BP was quantified. Results There was a significant positive correlation between retinal artery rPWV and MAP as expected (0.19 mm/s/mmHg, R2 = 0.59, p < 0.001). There was a positive correlation between retinal and aortic PWV (R2 = 0.09, p = 0.03). Conclusion ...
Rezaeian, M, Golzan, SM, Avolio, AP, Graham, S & Butlin, M 2020, 'The Association between Retinal and Central Pulse Wave Velocity in the Elderly', Artery Research, vol. 26, no. 3, pp. 148-153.
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Abstract Purpose The retina provides a non-invasive window to monitor microvascular circulation. Carotid-femoral Pulse Wave Velocity (cfPWV) is an indicator of large artery stiffness and is associated with systemic cardiovascular diseases. This study investigates whether Retinal artery PWV (rPWV) reflects cfPWV changes in an elderly cohort. Methods A total of 37 elderly participants (28 female, age 79 ± 5 years) were studied. Participants with a history of diabetes, glaucoma, and any neurological or eye-related disorders were excluded. Twenty four subjects were taking antihypertensive medication. A 60-s recording of retinal arterial diameter changes were captured (25 Hz frame rate, Dynamic Vessel Analyzer). Systolic blood pressure, Diastolic Blood Pressure (DBP), cfPWV and Intraocular Pressure (IOP) were measured. A custom-written algorithm was used to extract pulse amplitudes from retinal arterial diameters within one- and three-disc diameters from the optic disc. rPWV was designated as the ratio of the distance between two sites along the artery to the time delay between pulses. Predictors of rPWV were assessed by linear regression and parameter selection techniques. Results There was a positive correlation between rPWV and cfPWV (Pearson’s correlation coefficient 0.82, p < 0.001). In parameter selection models, cfPWV, transmural pressure (DBP–IOP), male sex, and IOP were isolated as predictors of rPWV. Conclusion This study found a positive correlation between rPWV and cfPWV in an elderly cohort. Th...
Roche, CD & Gentile, C 2020, 'Transplantation of a 3D Bioprinted Patch in a Murine Model of Myocardial Infarction', Journal of Visualized Experiments, vol. 2020, no. 163, pp. 1-12.
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© 2020 JoVE Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Testing regenerative properties of 3D bioprinted cardiac patches in vivo using murine models of heart failure via permanent left anterior descending (LAD) ligation is a challenging procedure and has a high mortality rate due to its nature. We developed a method to consistently transplant bioprinted patches of cells and hydrogels onto the epicardium of an infarcted mouse heart to test their regenerative properties in a robust and feasible way. First, a deeply anesthetized mouse is carefully intubated and ventilated. Following left lateral thoracotomy (surgical opening of the chest), the exposed LAD is permanently ligated and the bioprinted patch transplanted onto the epicardium. The mouse quickly recovers from the procedure after chest closure. The advantages of this robust and quick approach include a predicted 28-day mortality rate of up to 30% (lower than the 44% reported by other studies using a similar model of permanent LAD ligation in mice). Moreover, the approach described in this protocol is versatile and could be adapted to test bioprinted patches using different cell types or hydrogels where high numbers of animals are needed to optimally power studies. Overall, we present this as an advantageous approach which may change preclinical testing in future studies for the field of cardiac regeneration and tissue engineering.
Roche, CD, Brereton, RJL, Ashton, AW, Jackson, C & Gentile, C 2020, 'Current challenges in three-dimensional bioprinting heart tissues for cardiac surgery', European Journal of Cardio-Thoracic Surgery, vol. 58, no. 3, pp. 500-510.
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Abstract Summary Previous attempts in cardiac bioengineering have failed to provide tissues for cardiac regeneration. Recent advances in 3-dimensional bioprinting technology using prevascularized myocardial microtissues as ‘bioink’ have provided a promising way forward. This review guides the reader to understand why myocardial tissue engineering is difficult to achieve and how revascularization and contractile function could be restored in 3-dimensional bioprinted heart tissue using patient-derived stem cells.
Ryan, S, Kempton, T, Impellizzeri, FM & Coutts, AJ 2020, 'Training monitoring in professional Australian football: theoretical basis and recommendations for coaches and scientists', Science and Medicine in Football, vol. 4, no. 1, pp. 52-58.
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© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Australian football (AF) is a high-intensity field-based sport with regular collisions and intense physical demands such as jumping, tackling and jostling, resulting in neuromuscular fatigue and soreness, combined with external stressors (i.e., sponsorship, education, family). These can influence an athlete’s fatigue and recovery status, requiring an individualised approach to monitoring to optimise training readiness. Optimal readiness would reflect a condition where an athlete has no impairment of physical performance, no mental fatigue or excessive psychological distress. A theoretical framework exists for athlete monitoring that includes the quantification of training load and understanding individual ability to tolerate the training demands imposed by coaches. However, while this approach is thought to ultimately determine the readiness of a player for training and competition, it has not been tested empirically. The purpose of this review is to describe the theoretical basis that underpins athlete monitoring systems, and to provide an overview of their contribution to decision-making processes in planning and delivery of training in professional AF players. This review can assist coaches and scientists to gain a better understanding of commonly used monitoring measures and how the information derived from these sources is applied in a professional AF environment.
Ryan, S, Pacecca, E, Tebble, J, Hocking, J, Kempton, T & Coutts, AJ 2020, 'Measurement Characteristics of Athlete Monitoring Tools in Professional Australian Football', International Journal of Sports Physiology and Performance, vol. 15, no. 4, pp. 457-463.
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Purpose: To examine the measurement reliability and sensitivity of common athlete monitoring tools in professional Australian Football players. Methods: Test–retest reliability (noise) and weekly variation (signal) data were collected from 42 professional Australian footballers from 1 club during a competition season. Perceptual wellness was measured via questionnaires completed before main training sessions (48, 72, and 96 h postmatch), with players providing a rating (1–5 Likert scale) regarding their muscle soreness, sleep quality, fatigue level, stress, and motivation. Eccentric hamstring force and countermovement jumps were assessed via proprietary systems once per week. Heart rate recovery was assessed via a standard submaximal run test on a grass-covered field with players wearing a heart rate monitor. The heart rate recovery was calculated by subtracting average heart rate during final 10 seconds of rest from average heart rate during final 30 seconds of exercise. Typical test error was reported as coefficient of variation percentage (CV%) and intraclass coefficients. Sensitivity was calculated by dividing weekly CV% by test CV% to produce a signal to noise ratio. Results: All measures displayed acceptable sensitivity. Signal to noise ratio ranged from 1.3 to 11.1. Intraclass coefficients ranged from .30 to .97 for all measures. Conclusions: The heart rate recovery test, countermovement jump test, eccentric hamstring force test, and perceptual wellness all possess acceptable measurement sensitivity. Signal to noise ratio analysis is a novel method of assessing measurement characteristics of monitoring tools. These data can be used by coaches and scientists to identify meaningful changes in common measures of fitness and fatigue in profession...
Rzhevskiy, AS, Razavi Bazaz, S, Ding, L, Kapitannikova, A, Sayyadi, N, Campbell, D, Walsh, B, Gillatt, D, Ebrahimi Warkiani, M & Zvyagin, AV 2020, 'Rapid and Label-Free Isolation of Tumour Cells from the Urine of Patients with Localised Prostate Cancer Using Inertial Microfluidics', Cancers, vol. 12, no. 1, pp. 81-81.
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During the last decade, isolation of circulating tumour cells via blood liquid biopsy of prostate cancer (PCa) has attracted significant attention as an alternative, or substitute, to conventional diagnostic tests. However, it was previously determined that localised forms of PCa shed a small number of cancer cells into the bloodstream, and a large volume of blood is required just for a single test, which is impractical. To address this issue, urine has been used as an alternative to blood for liquid biopsy as a truly non-invasive, patient-friendly test. To this end, we developed a spiral microfluidic chip capable of isolating PCa cells from the urine of PCa patients. Potential clinical utility of the chip was demonstrated using anti-Glypican-1 (GPC-1) antibody as a model of the primary antibody in immunofluorescent assay for identification and detection of the collected tumour cells. The microchannel device was first evaluated using DU-145 cells in a diluted Dulbecco’s phosphate-buffered saline sample, where it demonstrated >85 (±6) % efficiency. The microchannel proved to be functional in at least 79% of cases for capturing GPC1+ putative tumour cells from the urine of patients with localised PCa. More importantly, a correlation was found between the amount of the captured GPC1+ cells and crucial diagnostic and prognostic parameter of localised PCa—Gleason score. Thus, the technique demonstrated promise for further assessment of its diagnostic value in PCa detection, diagnosis, and prognosis.
Sadeghi Rad, H, Bazaz, SR, Monkman, J, Ebrahimi Warkiani, M, Rezaei, N, O'Byrne, K & Kulasinghe, A 2020, 'The evolving landscape of predictive biomarkers in immuno‐oncology with a focus on spatial technologies', Clinical & Translational Immunology, vol. 9, no. 11.
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AbstractImmunotherapies have shown long‐lasting and unparalleled responses for cancer patients compared to conventional therapy. However, they seem to only be effective in a subset of patients. Therefore, it has become evident that a greater understanding of the tumor microenvironment (TME) is required to understand the nuances which may be at play for a favorable outcome to therapy. The immune contexture of the TME is an important factor in dictating how well a tumor may respond to immune checkpoint inhibitors. While traditional immunohistochemistry techniques allow for the profiling of cells in the tumor, this is often lost when tumors are analysed using bulk tissue genomic approaches. Moreover, the actual cellular proportions, cellular heterogeneity and deeper spatial distribution are lacking in characterisation. Advances in tissue interrogation technologies have given rise to spatially resolved characterisation of the TME. This review aims to provide an overview of the current methodologies that are used to profile the TME, which may provide insights into the immunopathology associated with a favorable outcome to immunotherapy.
Santos, J, Dolai, S, O’Rourke, MB, Liu, F, Padula, MP, Molloy, MP & Milthorpe, BK 2020, 'Quantitative Proteomic Profiling of Small Molecule Treated Mesenchymal Stem Cells Using Chemical Probes', International Journal of Molecular Sciences, vol. 22, no. 1, pp. 160-160.
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The differentiation of human adipose derived stem cells toward a neural phenotype by small molecules has been a vogue topic in the last decade. The characterization of the produced cells has been explored on a broad scale, examining morphological and specific surface protein markers; however, the lack of insight into the expression of functional proteins and their interactive partners is required to further understand the extent of the process. The phenotypic characterization by proteomic profiling allows for a substantial in-depth analysis of the molecular machinery induced and directing the cellular changes through the process. Herein we describe the temporal analysis and quantitative profiling of neural differentiating human adipose-derived stem cells after sub-proteome enrichment using a bisindolylmaleimide chemical probe. The results show that proteins enriched by the Bis-probe were identified reproducibly with 133, 118, 126 and 89 proteins identified at timepoints 0, 1, 6 and 12, respectively. Each temporal timepoint presented several shared and unique proteins relative to neural differentiation and their interactivity. The major protein classes enriched and quantified were enzymes, structural and ribosomal proteins that are integral to differentiation pathways. There were 42 uniquely identified enzymes identified in the cells, many acting as hubs in the networks with several interactions across the network modulating key biological pathways. From the cohort, it was found by gene ontology analysis that 18 enzymes had direct involvement with neurogenic differentiation.
Santos, J, Hubert, T & Milthorpe, BK 2020, 'Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways', Cells, vol. 9, no. 3, pp. 619-619.
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Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells.
Sarto, F, Impellizzeri, FM, Spörri, J, Porcelli, S, Olmo, J, Requena, B, Suarez-Arrones, L, Arundale, A, Bilsborough, J, Buchheit, M, Clubb, J, Coutts, A, Nabhan, D, Torres-Ronda, L, Mendez-Villanueva, A, Mujika, I, Maffiuletti, NA & Franchi, MV 2020, 'Impact of Potential Physiological Changes due to COVID-19 Home Confinement on Athlete Health Protection in Elite Sports: a Call for Awareness in Sports Programming', Sports Medicine, vol. 50, no. 8, pp. 1417-1419.
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Sayahi, M, Santos, J, El-Feki, H, Charvillat, C, Bosc, F, Karacan, I, Milthorpe, B & Drouet, C 2020, 'Brushite (Ca,M)HPO4, 2H2O doping with bioactive ions (M = Mg2+, Sr2+, Zn2+, Cu2+, and Ag+): a new path to functional biomaterials?', Materials Today Chemistry, vol. 16, pp. 100230-100230.
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© 2019 Elsevier Ltd Dicalcium phosphate dihydrate, DCPD (CaHPO4·2H2O), brushite, is an important calcium phosphate compound encountered in mineralized tissues and used in medicine, especially in bone cement formulations. However, the use of DCPD as direct implantable biomaterial has not received dedicated attention. In addition, the possibility to dope DCPD with biologically active ions to modulate its performances was not systematically explored. We have investigated in depth the doping of DCPD with Mg2+, Sr2+, Zn2+, Cu2+, and Ag+ ions. Clear modifications in terms of chemical composition, particle size, pore distribution, crystal morphology, and affinity for water were pointed out. Then, the samples were cultured with human adipose-derived stem cells to explore cytotoxicity and proliferation. Various behaviors were noticed dependent on the incorporated metal ions. Such DCPD compounds associated with bioactive metal ions, and particularly Ag+ and Zn2+, appear promising as a new family of reactive materials for use, as such or in combination, in bone-related applications.
Schweinsberg, S, Darcy, S & Beirman, D 2020, '‘Climate crisis’ and ‘bushfire disaster’: Implications for tourism from the involvement of social media in the 2019–2020 Australian bushfires', Journal of Hospitality and Tourism Management, vol. 43, pp. 294-297.
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Schweinsberg, S, McManus, P, Darcy, S & Wearing, S 2020, '‘Drought tourism’ as compassion', Annals of Tourism Research, vol. 83, pp. 102843-102843.
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Australia is experiencing a drought that for many farmers is the “worst they've experienced in their lifetime … the worst in 400 years” (Bedo, 2018). The negative effects of drought on rural communities is well documented (Edwards, Gray, & Hunter, 2015), as is the potential for knock-on effects to impact on the viability of rural communities, tourism destinations and their constituent industries (van Dijk et al., 2013). In spite of this, however, there is also recognition of a role for tourism in the promotion of rural community resilience (Gibson & Gordon, 2018). In Australia, many regions affected by drought are endeavouring to portray themselves from a tourism perspective as “open for business” (Ennion, 2019).With the media attempting to raise the profile of the drought affected regions and communities (e.g. Reardon, 2019), the focus of this paper is to consider media's opportunity to frame and promote a different type of tourist engagement with drought. Higgins Desbiolles (2006) has argued that tourism discourse needs to look beyond its industrial nature and instead also explore tourism's role in ensuring the wider public good. Forms of tourism including volunteer tourism have been recognised for their potential to aid the plight of the disadvantaged (Wearing & McGehee, 2013). Drawing on a representation of volunteer tourism in a drought-affected region (see Power, 2018), this paper will consider the role of the media in promoting a richer and deeper host-guest connection.
Shamshirian, A, Aref, AR, Yip, GW, Ebrahimi Warkiani, M, Heydari, K, Razavi Bazaz, S, Hamzehgardeshi, Z, Shamshirian, D, Moosazadeh, M & Alizadeh-Navaei, R 2020, 'Diagnostic value of serum HER2 levels in breast cancer: a systematic review and meta-analysis', BMC Cancer, vol. 20, no. 1, p. 1049.
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Abstract Background Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods. Methods We performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Results Fourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82–65.28), but reasonable specificity of 79.27 (95%CI 73.02–85.51), accuracy of 72.06 (95%CI 67.04–77.08) and AUC of 0.79 (95%CI 0.66–0.92). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16–68.20), NPV (NPV: 76.93, 95%CI 69.56–84.31), PLR (PLR: 2.10, 95%CI 1.69–2.50) and NLR (NLR: 0.58, 95%CI 0.44–0.71). Conclusion Our findings revealed that although serum HER-2 le...
Shanahan, M, Seddon, J, Ritter, A & De Abreu Lourenco, R 2020, 'Valuing families' preferences for drug treatment: a discrete choice experiment', Addiction, vol. 115, no. 4, pp. 690-699.
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AbstractBackground and AimsThe burden on family members of those who are dependent on illicit drugs is largely unidentified, despite the presence of significant negative financial, health and social impacts. This makes it difficult to provide appropriate services and support. This study aimed to assess the preferences for treatment attributes for heroin dependence among family members affected by the drug use of a relative and to obtain a measure of the intangible economic benefit.DesignDiscrete choice experiment. Data were analysed using mixed logit which accounted for repeated responses.SettingAustralia.ParticipantsEligible participants were Australian residents aged 18+ years with a relative with problematic drug use. Complete data on 237 respondents were analysed; 21 invalid responses were deleted.MeasurementsParticipant preference for likelihood of staying in treatment, family conflict, own health status, contact with police and monetary contribution to a charitable organization providing treatment.FindingsAll attributes were significant, and the results suggest that there was a preference for longer time in treatment, less family discord, better own health status, less likelihood of their relative encountering police and, while they were willing to contribute to a charity for treatment to be available, they prefer to pay less, not more. In order of relative importance, participants were willing to pay an additional A$4.46 [95% confidence interval (CI) = 3.33–5.60] for treatment which resulted in an additional 1% of heroin users staying in treatment for longer than 3 month...
Shariflou, S, Agar, A, Rose, K, Bowd, C & Golzan, SM 2020, 'Objective Quantification of Spontaneous Retinal Venous Pulsations Using a Novel Tablet-Based Ophthalmoscope', Translational Vision Science & Technology, vol. 9, no. 4, pp. 19-19.
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Purpose:Dynamic assessment of retinal vascular characteristics can aid in identifying glaucoma-specific biomarkers. More specifically, a loss of spontaneous retinal venous pulsations (SVPs) has been reported in glaucoma, but a lack of readily available tools has limited the ability to explore the full potential of SVP analysis in glaucoma assessment. Advancements in smart technology have paved the way for the development of portable, noninvasive, and inexpensive imaging modalities. By combining off-the-shelf optical elements and smart devices, the current study aims to determine whether SVPs can be detected and quantified using a novel tablet-based ophthalmoscope in glaucoma and glaucoma suspects. Methods:Thirty patients, including 21 with confirmed glaucoma (9 men; average age 75 ± 8 years) and 9 glaucoma suspects (5 men; average age 64 ± 9 years), were studied. All patients had intraocular pressure measurements, Humphrey visual field assessment, optical coherence tomography, and a 10-second videoscopy of the retinal circulation. The retinal vasculature recordings (46° field of view at 30 frames per second) were analyzed to extract SVP amplitudes. Results:SVPs were detected and quantified in 100% of patients with glaucoma and those with suspected glaucoma using the novel device. The average SVP amplitudes in glaucoma and glaucoma suspects were 42.6% ± 10.7% and 34% ± 6.7%, respectively. Conclusions:Our results suggest that a novel tablet-based ophthalmoscope can aid in documenting and objectively quantifying SVPs in all patients. Translational Relevance:Outcomes of this study provide an innovative, portable, noninvasive, and inexpensive solution for objective assessment of SVPs, which may have clinical relevance in glaucoma screening.
Shell, SJ, Slattery, K, Clark, B, Broatch, JR, Halson, S, Kellmann, M & Coutts, AJ 2020, 'Perceptions and use of recovery strategies: Do swimmers and coaches believe they are effective?', Journal of Sports Sciences, vol. 38, no. 18, pp. 2092-2099.
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Shires, A, Sharpe, L, Davies, JN & Newton John, T 2020, 'The efficacy of mindfulness based interventions in acute pain: a systematic review and meta-analysis.', Pain, vol. 161, no. 8, pp. 1698-1707.
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Recent meta-analyses have shown MBIs to be effective for chronic pain, but no pooled estimates of the effect of MBIs on acute pain are available. This meta-analysis was conducted to fill that gap. A literature search was conducted in four databases. Articles were eligible if they reported on randomized controlled trials of MBIs for people with acute pain and included one of the following outcomes: pain severity, pain threshold, pain tolerance or pain-related distress. Two authors independently extracted the data, assessed risk of bias and provided GRADE ratings. Twenty-two studies were included. There was no evidence of an effect of MBIs on the primary outcome of pain severity in clinical (Hedge's g=0.52; [95%CI -0.241, 1.280]) or experimental settings (Hedge's g= 0.043; 95%CI [-0.161, 0.247]). There was a beneficial effect of MBIs on pain tolerance (Hedge's g=0.68; 95%CI [0.157, 1.282]) and pain threshold (Hedge's g=0.72; 95%CI [0.210, 1.154]) in experimental studies. There was no evidence of an effect of MBIs compared to control for pain-related distress in clinical (Hedge's g=0.159; 95%CI [-0.018, 0.419]) or experimental settings (Hedge's g=0.439; 95%CI [-0.164, 0.419]). GRADE assessment indicated that except for pain tolerance, the data were of low or very low quality. There is moderate evidence that MBIs are efficacious in increasing pain tolerance and weak evidence for pain threshold. However, there is an absence of good quality evidence for the efficacy of MBIs for reducing the pain severity or pain-related distress in either clinical or experimental settings.
Shrestha, J, Razavi Bazaz, S, Aboulkheyr Es, H, Yaghobian Azari, D, Thierry, B, Ebrahimi Warkiani, M & Ghadiri, M 2020, 'Lung-on-a-chip: the future of respiratory disease models and pharmacological studies', Critical Reviews in Biotechnology, vol. 40, no. 2, pp. 213-230.
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© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group. Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs; and in the case of this review, the lung. Lung-on-a-chip models result in a more accurate reflection compared to conventional in vitro models. Pharmaceutical drug testing methods traditionally use animal models in order to evaluate pharmacological and toxicological responses to a new agent. However, these responses do not directly reflect human physiological responses. In this review, current and future applications of the lung-on-a-chip in the respiratory system will be discussed. Furthermore, the limitations of current conventional in vitro models used for respiratory disease modeling and drug development will be addressed. Highlights of additional translational aspects of the lung-on-a-chip will be discussed in order to demonstrate the importance of this subject for medical research.
Siva, S, Bressel, M, Kron, T, Mai, T, Le, HV, Montgomery, R, Hardcastle, N, Rezo, A, Gill, S, Higgs, BG, Pryor, DI, De Abreu Lourenco, R, Awad, R, Chesson, B, Eade, TN, Skala, M, Sasso, G, Wong, W, Vinod, S & Ball, D 2020, 'Stereotactic Ablative Fractionated Radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the Lung: A Randomized Phase II Trial', International Journal of Radiation Oncology*Biology*Physics, vol. 108, no. 3, pp. S3-S4.
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Skarding, J, Gabrys, B & Musial, K 2020, 'Foundations and modelling of dynamic networks using Dynamic Graph Neural Networks: A survey', in IEEE Access, vol. 9, pp. 79143-79168.
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Dynamic networks are used in a wide range of fields, including social networkanalysis, recommender systems, and epidemiology. Representing complex networksas structures changing over time allow network models to leverage not onlystructural but also temporal patterns. However, as dynamic network literaturestems from diverse fields and makes use of inconsistent terminology, it ischallenging to navigate. Meanwhile, graph neural networks (GNNs) have gained alot of attention in recent years for their ability to perform well on a rangeof network science tasks, such as link prediction and node classification.Despite the popularity of graph neural networks and the proven benefits ofdynamic network models, there has been little focus on graph neural networksfor dynamic networks. To address the challenges resulting from the fact thatthis research crosses diverse fields as well as to survey dynamic graph neuralnetworks, this work is split into two main parts. First, to address theambiguity of the dynamic network terminology we establish a foundation ofdynamic networks with consistent, detailed terminology and notation. Second, wepresent a comprehensive survey of dynamic graph neural network models using theproposed terminology
Sritharan, K, Chamoli, U, Kuan, J & Diwan, AD 2020, 'Assessment of degenerative cervical stenosis on T2-weighted MR imaging: sensitivity to change and reliability of mid-sagittal and axial plane metrics', Spinal Cord, vol. 58, no. 2, pp. 238-246.
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STUDY DESIGN:A retrospective cross-sectional study. OBJECTIVE:To assess the sensitivity to change and reliability of various mid-sagittal and axial plane metrics in the assessment of patients with single-level degenerative cervical stenosis on T2-weighted MR imaging. SETTING:A diagnostic MR imaging facility in Sydney (Australia). METHODS:We retrospectively reviewed T2-weighted MR images of 85 consecutive patients (48 M and 37 F) with single-level degenerative cervical stenosis. Canal compromise and cord compression were evaluated using three mid-sagittal plane metrics (M1, M2, and M3) and two axial plane metrics (M4 and M5), at the level of stenosis and nonstenotic cephalad and caudal levels (controls). Sensitivity to change (SC) for each metric was evaluated as the percentage deviation of the measured value from the estimated normal value based on cephalad and caudal controls. Reliability for each metric was evaluated using intraclass correlation coefficients. RESULTS:Degenerative cervical stenosis showed a bimodal distribution peaking at C5-6 (n = 32) and C3-4 (n = 29) levels. The changes in the canal and cord geometry along the rostrocaudal axis were inconsistent. Across all individual subjects (reflecting a range of stenosis severity), M3 (-32.87% ± 10.60%) was more sensitive to change compared with M1 (16.64% ± 16.48%) and M2 (-23.95% ± 11.12%). Similarly, M4 (-24.62% ± 12.17%) was more sensitive to change compared with M5 (-6.71% ± 11.08%). The level of reliability was "moderate" to "excellent" for mid-sagittal plane measurements, and "poor" to "excellent" for axial plane measurements. CONCLUSION:Changes in canal dimensions in the mid-sagittal plane and cord shape in the axial plane are sensitive indicators of degenerative cervical stenosis on T2-weighted MR images.
Stone, E, Rankin, N, Currow, D, Fong, KM, Phillips, JL & Shaw, T 2020, 'Optimizing lung cancer MDT data for maximum clinical impact—a scoping literature review', Translational Lung Cancer Research, vol. 9, no. 4, pp. 1629-1638.
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Multidisciplinary care in is widely recommended as best practice for lung cancer in many countries and jurisdictions. A number of studies suggest multidisciplinary care benefits patient outcomes, with analyses based on a range of data sources including national, state and local registries as well as multidisciplinary team meeting (MDT)-based data collections, often focused on different questions depending on data sources. MDT data collection and linkage are not standardized and not routine although data collection and feedback are specifically recommended by at least one statutory body. We performed a scoping review of current evidence for lung cancer MDT data collection and analysis, to identify discrete strategies through illustrative examples and to make recommendations for future approaches. Thirteen studies were identified that presented lung cancer MDT-related clinical outcomes, three included MDTs from multiple tumour streams while 10 studies focussed on lung cancer MDT meetings. Eleven studies measured the effect of MDT discussion on clinical outcomes of which eight were positive. Data sources included MDT records (3 studies), medical or hospital records (3 studies), institutional registries (5 studies) and state or national administrative datasets (6 studies), with some overlap. Examples of studies based on different data sources (local MDT, institutional registry, national registry) exemplified the different types of clinical research questions appropriate for each data source. While MDT data collection is not well-defined, the importance of clinical audit and data feedback and the potential for real-time analysis to improve outcomes deserve further investigation. Optimized datasets and linkage strategies are likely to maximize benefits for patients.
Stone, E, Rankin, NM, Vinod, SK, Nagarajah, M, Donnelly, C, Currow, DC, Fong, KM, Phillips, JL & Shaw, T 2020, 'Clinical impact of data feedback at lung cancer multidisciplinary team meetings: A mixed methods study', Asia-Pacific Journal of Clinical Oncology, vol. 16, no. 1, pp. 45-55.
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AbstractAimMultidisciplinary team (MDT) meetings can facilitate optimal lung cancer care, yet details of structured data collection and feedback remain sparse. This study aimed to investigate data collection and the impact of feedback to lung cancer MDTs.MethodsA mixed‐methods study using pre and post‐test surveys, semistructured interviews, and observation to evaluate data collection and response to modeled data feedback in three Australian lung cancer MDTs at different locations and development stage (site A: outer metropolitan, established; site B, outer metropolitan, new; and site C, inner metropolitan, established).ResultsMDT attendees (range 13‐25) discussed 5‐8 cases per meeting. All sites collected data prospectively (80% prepopulated) into local oncology medical information systems. The pretest survey had 17 respondents in total (88% clinicians). At sites A and C, 100% of respondents noted regular data audits, occasional at site B. Regular audit data included number of cases, stage, final diagnosis, and time to diagnosis and treatment. The post‐test survey had 25 respondents in total, all clinicians. The majority (88‐96%) of respondents found modeled data easy to interpret, relevant to clinical practice and the MDT, and welcomed future regular data presentations (as rated on a 5‐point Likert scale mean weighted average 4.5 where > 4 demonstrates agreement). Semistructured interviews identified five major themes for MDTs: current practice, attitudes, enablers, barriers, and benefits for the MDT.ConclusionsMDT teams exhibited positive responses to modeled data feedback. Key characteristics of MDT data were identified and may assist with future team research and development.
Su, D, Vidal-Calleja, T & Miro, JV 2020, 'Asynchronous microphone arrays calibration and sound source tracking', Autonomous Robots, vol. 44, no. 2, pp. 183-204.
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© 2019, Springer Science+Business Media, LLC, part of Springer Nature. In this paper, we proposed an optimisation method to solve the problem of sound source localisation and calibration of an asynchronous microphone array. This method is based on the graph-based formulation of the simultaneous localisation and mapping problem. In this formulation, a moving sound source is considered to be observed from a static microphone array. Traditional approaches for sound source localisation rely on the well-known geometrical information of the array and synchronous readings of the audio signals. Recent work relaxed these two requirements by estimating the temporal offset between pair of microphones based on the assumption that the clock timing of each microphone is exactly the same. This assumption requires the sound cards to be identically manufactured, which in practice is not possible to achieve. Hereby an approach is proposed to jointly estimate the array geometrical information, time offset and clock difference/drift rate of each microphone together with the location of a moving sound source. In addition, an observability analysis of the system is performed to investigate the most suitable configuration for sound source localisation. Simulation and experimental results are presented, which prove the effectiveness of the proposed methodology.
Sullivan, C, Kempton, T, Ward, P & Coutts, AJ 2020, 'Career Performance Trajectories of Professional Australian Football Players', International Journal of Sports Physiology and Performance, vol. 15, no. 10, pp. 1363-1368.
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Purpose: To develop position-specific career performance trajectories and determine the age of peak performance of professional Australian Football players. Methods: Match performance data (Australian Football League [AFL] Player Rank) were collected for Australian Football players drafted via the AFL National Draft between 1999 and 2015 (N = 207). Players were subdivided into playing positions: forwards (n = 60; age 23 [3] y), defenders (n = 71; age 24 [4] y), midfielders (n = 58; age 24 [4] y), and ruckmen (n = 18; age 24 [3] y). Linear mixed models were fitted to the data to estimate individual career trajectories. Results: Forwards, midfielders, and defenders experienced peak match performance earlier than ruckmen (24–25 vs 27 y). Midfielders demonstrated the greatest between-subjects variability (intercept 0.580, age 0.0286) in comparison with ruckmen, who demonstrated the least variability (intercept 0.112, age 0.005) in AFL Player Rank throughout their careers. Age had the greatest influence on the career trajectory of midfielders (β [SE] = 0.226 [0.025], T = 9.10, P < .01) and the least effect on ruckmen (β [SE] = 0.114 [0.049], T = 2.30, P = .02). Conclusions: Professional Australian Football players peak in match performance between 24 and 27 years of age with age, having the greatest influence on the match performance of midfielders and the least on ruckmen.
Sullivan, C, Kempton, T, Ward, P & Coutts, AJ 2020, 'The efficacy of talent selection criteria in the Australian Football League', Journal of Sports Sciences, vol. 38, no. 7, pp. 773-779.
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This study investigated the association between talent selection criteria, draft order and match performance in professional Australian Football players. Physical performance results from the Australian Football League (AFL) National Draft combine and non-performance based talent selection criteria were collated for all players drafted in the National Draft with selections 1-80 between 2003 and 2008 (n = 318). Match performance was assessed via the AFL Player Ranking metric that was provided by a commercial statistical provider (Champion Data Pty Ltd). A combination of stepwise multiple regression and linear mixed model analyses examined the influence of National Draft combine physical performance assessments and non-performance based talent selection criteria on draft order and future match performance. Earlier draft selection was associated with Under-18 all Australian team selection, height, Under-18 National Championship participation and indigenous status. The 20 m sprint and state of origin were associated with later draft selection. Under-18 all Australian team selection increased both Player Ranking/game and total Player Ranking. Under-18 all Australian team selection displays efficacy for selecting players with the potential for success.
Suvakov, S, Richards, C, Nikolic, V, Simic, T, McGrath, K, Krasnodembskaya, A & McClements, L 2020, 'Emerging Therapeutic Potential of Mesenchymal Stem/Stromal Cells in Preeclampsia', Current Hypertension Reports, vol. 22, no. 5, pp. 37-37.
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Purpose of Review
Preeclampsia is a dangerous pregnancy condition affecting both the mother and offspring. It is a multifactorial disease with poorly understood pathogenesis, lacking effective treatments. Maternal immune response, inflammation and oxidative stress leading to endothelial dysfunction are the most prominent pathogenic processes implicated in preeclampsia development. Here, we give a detailed overview of the therapeutic applications and mechanisms of mesenchymal stem/stromal cells (MSCs) as a potential new treatment for preeclampsia.
Recent Findings
MSCs have gained growing attention due to low immunogenicity, easy cultivation and expansion in vitro. Accumulating evidence now suggests that MSCs act primarily through their secretomes facilitating paracrine signalling that leads to potent immunomodulatory, pro-angiogenic and regenerative therapeutic effects.
Summary
MSCs have been studied in different animal models of preeclampsia demonstrating promising result, which support further investigations into the therapeutic effects and mechanisms of MSC-based therapies in preeclampsia, steering these therapies into clinical trials.
Syed, MS, Mirakhorli, F, Marquis, C, Taylor, RA & Warkiani, ME 2020, 'Particle movement and fluid behavior visualization using an optically transparent 3D-printed micro-hydrocyclone', Biomicrofluidics, vol. 14, no. 6, pp. 064106-064106.
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A hydrocyclone is a macroscale separation device employed in various industries, with many advantages, including high-throughput and low operational costs. Translating these advantages to microscale has been a challenge due to the microscale fabrication limitations that can be surmounted using 3D printing technology. Additionally, it is difficult to simulate the performance of real 3D-printed micro-hydrocyclones because of turbulent eddies and the deviations from the design due to printing resolution. To address these issues, we propose a new experimental method for the direct observation of particle motion in 3D printed micro-hydrocyclones. To do so, wax 3D printing and soft lithography were used in combination to construct a transparent micro-hydrocyclone in a single block of polydimethylsiloxane. A high-speed camera and fluorescent particles were employed to obtain clear in situ images and to confirm the presence of the vortex core. To showcase the use of this method, we demonstrate that a well-designed device can achieve a 95% separation efficiency for a sample containing a mixture of (desired) stem cells and (undesired) microcarriers. Overall, we hope that the proposed method for the direct visualization of particle trajectories in micro-hydrocyclones will serve as a tool, which can be leveraged to accelerate the development of micro-hydrocyclones for biomedical applications.
Tan, Y, Johnson, M, Zhou, J, Zhao, Y, Kamal, MA & Qu, X 2020, 'Antrodia cinnamomea Inhibits Growth and Migration of Lung Cancer Cells through Regulating p53-Bcl2 and MMPs Pathways', The American Journal of Chinese Medicine, vol. 48, no. 08, pp. 1941-1953.
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Antrodia cinnamomea has been shown to possess antitumor activity. This study investigated the effects and mechanisms of Antrodia cinnamomea extract (ACE) on growth and migration of human non-small cell lung cancer A549 cells. The effect of ACE on cell viability was determined by MTT assay and fluorescent live-cell imaging. The apoptotic effect of ACE was determined by cell cycle distribution using flow cytometry. A P53-mediated apoptosis pathway was identified by measuring protein expression of p53 and Bcl-2 with Western blotting. Additionally, mRNA expression of p53 and Bcl-2 and Bax was detected by qRT-PCR. The effect of ACE on cancer cell migration was confirmed by a wound-healing assay. Expression of MMP-2 and MMP-9 at the protein and gene levels was determined by western blot and qRT-PCR analysis. This study demonstrates the inhibitory effect of ACE on A549 cell proliferation in a dose-response manner with an [Formula: see text]. It was determined that ACE concentration at [Formula: see text] induced cell cycle arrest at S phase in A549 cells. The apoptosis-regulating protein p53 expression was enhanced and also associated with the downregulation of Bcl-2 in ACE treatment cells. The mRNA expression of p53 and Bcl-2 associated with Bxa was consistent with protein expression. The inhibition of migration of cancer cells treated with ACE was clearly evident. At the same time, suppression of expression of MMP-2 and MMP-9 at protein and mRNA levels was observed. The findings of this study highlight ACE as a potential agent of adjuvant therapy for lung cancer.
Tavakoli, J, Diwan, AD & Tipper, JL 2020, 'Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus', International Journal of Molecular Sciences, vol. 21, no. 14, pp. 4889-4889.
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Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have failed so far and no effective strategy has translated into a successful clinical outcome. Of particular significance, the failure of strategies to repair the AF has been a major drawback in the regeneration of IVD and nucleus replacement. It is unlikely to secure regenerative mediators (cells, genes, and biomolecules) and artificial nucleus materials after injection with an unsealed AF, as IVD is exposed to significant load and large deformation during daily activities. The AF defects strongly change the mechanical properties of the IVD and activate catabolic routes that are responsible for accelerating IVD degeneration. Therefore, there is a strong need to develop effective therapeutic strategies to prevent or reconstruct AF damage to support operational IVD regenerative strategies and nucleus replacement. By the way of this review, repair and regenerative strategies for AF reconstruction, their current status, challenges ahead, and future outlooks were discussed.
Tavakoli, J, Diwan, AD & Tipper, JL 2020, 'Elastic fibers: The missing key to improve engineering concepts for reconstruction of the Nucleus Pulposus in the intervertebral disc', Acta Biomaterialia, vol. 113, pp. 407-416.
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Tavakoli, J, Diwan, AD & Tipper, JL 2020, 'The ultrastructural organization of elastic fibers at the interface of the nucleus and annulus of the intervertebral disk', Acta Biomaterialia, vol. 114, pp. 323-332.
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There has been no study to describe the ultrastructural organization of elastic fibers at the interface of the nucleus pulposus and annulus fibrosus of the intervertebral disk (IVD), a region called the transition zone (TZ). A previously developed digestion technique was optimized to eliminate cells and non-elastin ECM components except for the elastic fibers from the anterolateral (AL) and posterolateral (PL) regions of the TZ in ovine IVDs. Not previously reported, the current study identified a complex elastic fiber network across the TZ for both AL and PL regions. In the AL region, this network consisted of major thick elastic fibers (≈ 1 µm) that were interconnected with delicate (< 200 nm) elastic fibers. While the same ultrastructural organization was observed in the PL region, interestingly the size of the elastic fibers was smaller (< 100 nm) compared to those that were located in the AL region. Quantitative analysis of the elastic fibers revealed significant differences in the size (p < 0.001) and the orientation of elastic fibers (p = 0.001) between the AL and PL regions, with a higher orientation and larger size of elastic fibers observed in the AL region. The gradual elimination of cells and non-elastin extracellular matrix components identified that elastic fibers in the TZ region in combination with the extracellular matrix created a honeycomb structure that was more compact at the AF interface compared to that located close to the NP. Three different symmetrically organized angles of rotation (0⁰ and ±90⁰) were detected for the honeycomb structure at both interfaces, and the structure was significantly orientated at the TZ-AF compared to the TZ-NP interface (p = 0.003).
Tavakoli, J, Joseph, N, Chuah, C, Raston, CL & Tang, Y 2020, 'Vortex fluidic enabling and significantly boosting light intensity of graphene oxide with aggregation induced emission luminogen', Materials Chemistry Frontiers, vol. 4, no. 7, pp. 2126-2130.
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We have discovered a novel and cost-effective approach to produce GO/aggregation-induced emission demonstrating high fluorescent performance.
Tavakoli, J, Pye, S, Reza, AHMM, Xie, N, Qin, J, Raston, CL, Tang, BZ & Tang, Y 2020, 'Tuning aggregation-induced emission nanoparticle properties under thin film formation', Materials Chemistry Frontiers, vol. 4, no. 2, pp. 537-545.
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The preparation of AIE nanoparticles under thin film formation controls their size and the associated fluorescent intensity, with the smaller nanoparticles significantly increasing brightness.
Tavakoli, J, Raston, CL & Tang, Y 2020, 'Tuning Surface Morphology of Fluorescent Hydrogels Using a Vortex Fluidic Device', Molecules, vol. 25, no. 15, pp. 3445-3445.
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In recent decades, microfluidic techniques have been extensively used to advance hydrogel design and control the architectural features on the micro- and nanoscale. The major challenges with the microfluidic approach are clogging and limited architectural features: notably, the creation of the sphere, core-shell, and fibers. Implementation of batch production is almost impossible with the relatively lengthy time of production, which is another disadvantage. This minireview aims to introduce a new microfluidic platform, a vortex fluidic device (VFD), for one-step fabrication of hydrogels with different architectural features and properties. The application of a VFD in the fabrication of physically crosslinked hydrogels with different surface morphologies, the creation of fluorescent hydrogels with excellent photostability and fluorescence properties, and tuning of the structure–property relationship in hydrogels are discussed. We conceive, on the basis of this minireview, that future studies will provide new opportunities to develop hydrogel nanocomposites with superior properties for different biomedical and engineering applications.
Tavakoli, J, Raston, CL, Ma, Y & Tang, Y 2020, 'Vortex fluidic mediated one-step fabrication of polyvinyl alcohol hydrogel films with tunable surface morphologies and enhanced self-healing properties', Science China Materials, vol. 63, no. 7, pp. 1310-1317.
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Tavakoli, J, Wang, J, Chuah, C & Tang, Y 2020, 'Natural-based Hydrogels: A Journey from Simple to Smart Networks for Medical Examination', Current Medicinal Chemistry, vol. 27, no. 16, pp. 2704-2733.
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Natural hydrogels, due to their unique biological properties, have been used extensively for various medical and clinical examinations that are performed to investigate the signs of disease. Recently, complex-crosslinking strategies improved the mechanical properties and advanced approaches have resulted in the introduction of naturally derived hydrogels that exhibit high biocompatibility, with shape memory and self-healing characteristics. Moreover, the creation of self-assembled natural hydrogels under physiological conditions has provided the opportunity to engineer fine-tuning properties. To highlight recent studies of natural-based hydrogels and their applications for medical investigation, a critical review was undertaken using published papers from the Science Direct database. This review presents different natural-based hydrogels (natural, natural-synthetic hybrid and complex-crosslinked hydrogels), their historical evolution, and recent studies of medical examination applications. The application of natural-based hydrogels in the design and fabrication of biosensors, catheters and medical electrodes, detection of cancer, targeted delivery of imaging compounds (bioimaging) and fabrication of fluorescent bioprobes is summarised here. Without doubt, in future, more useful and practical concepts will be derived to identify natural-based hydrogels for a wide range of clinical examination applications.
Taylor, L, Chrismas, BCR, Stevens, CJ, Coutts, AJ & Henderson, MJ 2020, 'Elite Female Rugby Sevens Tournament Match-Play - Core Temperature Changes', Medicine & Science in Sports & Exercise, vol. 52, no. 7S, pp. 968-968.
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Tee, AE, Ciampa, OC, Wong, M, Fletcher, JI, Kamili, A, Chen, J, Ho, N, Sun, Y, Carter, DR, Cheung, BB, Marshall, GM, Liu, PY & Liu, T 2020, 'Combination therapy with the CDK7 inhibitor and the tyrosine kinase inhibitor exerts synergistic anticancer effects against MYCN‐amplified neuroblastoma', International Journal of Cancer, vol. 147, no. 7, pp. 1928-1938.
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Patients with neuroblastoma due to MYCN oncogene amplification and consequent N‐Myc oncoprotein overexpression have very poor prognosis. The cyclin‐dependent kinase 7 (CDK7)/super‐enhancer inhibitor THZ1 suppresses MYCN gene transcription, reduces neuroblastoma cell proliferation, but does not cause significant cell death. The protein kinase phosphatase 1 nuclear targeting subunit (PNUTS) has recently been shown to interact with c‐Myc protein and suppresses c‐Myc protein degradation. Here we screened the U.S. Food and Drug Administration‐Approved Oncology Drugs Set V from the National Cancer Institute, and identified tyrosine kinase inhibitors (TKIs), including ponatinib and lapatinib, as the Approved Oncology Drugs exerting the best synergistic anticancer effects with THZ1 in MYCN‐amplified neuroblastoma cells. Combination therapy with THZ1 and ponatinib or lapatinib synergistically induced neuroblastoma cell apoptosis, while having little effects in normal nonmalignant cells. Differential gene expression analysis identified PNUTS as one of the genes most synergistically reduced by the combination therapy. Reverse transcription polymerase chain reaction and immunoblot analyses confirmed that THZ1 and the TKIs synergistically downregulated PNUTS mRNA and protein expression and reduced N‐Myc protein but not N‐Myc mRNA expression. In addition, PNUTS knockdown resulted in decreased N‐Myc protein but not mRNA expression and decreased MYCN‐amplified neuroblastoma cell proliferation and survival. As CDK7 inhibitors are currently under clinical evaluation in patients, our data suggest the addition of the TKI ponatinib or lapatinib in CDK7 inhibitor clinical trials in patients.
Tew, XN, Xin Lau, NJ, Chellappan, DK, Madheswaran, T, Zeeshan, F, Tambuwala, MM, Aljabali, AAA, Balusamy, SR, Perumalsamy, H, Gupta, G, Oliver, BG, Hsu, A, Wark, P, Reddy, K, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases', Chemico-Biological Interactions, vol. 317, pp. 108947-108947.
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© 2020 Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.
Thompson, CJ, Noon, M, Towlson, C, Perry, J, Coutts, AJ, Harper, LD, Skorski, S, Smith, MR, Barrett, S & Meyer, T 2020, 'Understanding the presence of mental fatigue in English academy soccer players', Journal of Sports Sciences, vol. 38, no. 13, pp. 1524-1530.
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Research has demonstrated that induced mental fatigue impairs soccer-specific technical, tactical and physical performance in soccer players. The findings are limited by the lack of elite players and low ecological validity of the tasks used to induce mental fatigue, which do not resemble the cognitive demands of soccer. The current study collected survey data from English academy soccer players (n = 256; age groups - U14 - U23), with questions comprising of five themes (descriptors of physical and mental fatigue, travel, education, match-play and fixture congestion). The survey consisted of multiple choice responses, checkboxes and blinded/unblinded (for duration based questions) 0-100 arbitrary unit (AU) slider scales. Listening to music (81.6% of players), using social media (58.3%) and watching videos (34.3%) were the most common pre-match activities. Pre-match subjective mental fatigue was low (18.7±18.8 AU), and most frequently reported at the end of a match (47±26 AU) and remained elevated 24-hours post-match (36±27 AU). Travel (29±24 AU), fixture congestion (44±25 AU) and education (30±26 AU) demonstrated a low to moderate presence of subjective mental fatigue. These findings provide an overview of activities performed by English academy soccer players pre-match, and demonstrate that mental fatigue is experienced as a result of match-play.
Tonga, KO, Chapman, DG, Farah, CS, Oliver, BG, Zimmermann, SC, Milne, S, Sanai, F, Jetmalani, K, Berend, N, Thamrin, C & King, GG 2020, 'Reduced lung elastic recoil and fixed airflow obstruction in asthma', Respirology, vol. 25, no. 6, pp. 613-619.
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ABSTRACTBackground and objectiveFixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma.MethodsNon‐smoking asthmatic subjects aged >40 years, treated with 2 months of high‐dose inhaled corticosteroid/long‐acting beta‐agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs5) and respiratory system reactance at 5 Hz (Xrs5) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure–volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), Rrs5 and Xrs5 were assessed.ResultsEighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z‐score) post‐bronchodilator FEV1: −2.2 ± 0.5, FVC: −0.7 ± 1.0, FEV1/FVC: −2.6 ± 0.7) and by increased Rrs5 (median (IQR) z‐score) 2.7 (1.9 to 3.2) and decreased Xrs5: −4.1(−2.4 to −7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV1/FVC correlated negatively with K (rs = −...
Torgbenu, E, Luckett, T, Buhagiar, MA, Chang, S & Phillips, JL 2020, 'Prevalence and incidence of cancer related lymphedema in low and middle-income countries: a systematic review and meta-analysis', BMC Cancer, vol. 20, no. 1.
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AbstractBackgroundLittle is known about the prevalence and incidence in low and middle-income countries (LMICs) of secondary lymphedema due to cancer. The purpose of the study is to estimate the prevalence and incidence in LMICs of secondary lymphedema related to cancer and/or its treatment(s) and identify risk factors.MethodA systematic review and meta-analysis was conducted. Medline, EMBASE and CINAHL were searched in June 2019 for peer-reviewed articles that assessed prevalence and/or incidence of cancer-related lymphedema in LMICs. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Estimates of pooled prevalence and incidence estimates were calculated with 95% confidence intervals (CI), with sub-group analyses grouping studies according to: country of origin, study design, risk of bias, setting, treatment, and lymphedema site and measurement. Heterogeneity was measured usingX2and I2, with interpretation guided by the Cochrane Handbook for Systematic Reviews.ResultsOf 8766 articles, 36 were included. Most reported on arm lymphedema secondary to breast cancer treatment (n = 31), with the remainder reporting on leg lymphedema following gynecological cancer treatment (n = 5). Arm lymphedema was mostly measured by arm circumference (n = 16/31 studies), and leg lymphedema through self-report (n = 3/5 studies). Eight studies used more than one lymphedema measurement. Only two studies that measured prevalence of leg lymphedema could be included in a meta-analysis (pooled prevalence =10.0, 95% CI 7.0–13.0,I...
Tran, T, Bliuc, D, O’Donoghue, S, Hansen, L, Abrahamsen, B, Bergh, JVD, Geel, TV, Geusens, P, Vestergaard, P, Nguyen, TV, Eisman, JA & Center, J 2020, 'OR13-03 Understanding Why Older People with Low Trauma Fractures Die Prematurely', Journal of the Endocrine Society, vol. 4, no. Supplement_1.
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Abstract There is increasing evidence that all proximal and not just hip fractures are associated with increased mortality risk. However, the cause of this increased mortality is unknown. We sought to determine the post-fracture trajectories of subsequent hospital admissions and mortality to develop an understanding of why patients with non-hip fractures die prematurely. This nationwide Danish population-based study included all individuals aged 50+ years who sustained an incident fragility fracture between 2001 and 2014. High-trauma fractures or individuals with fracture prior to 2001 were excluded. Fracture patients were matched 1:4 by sex, age and comorbidity status with non-fracture subjects alive at the time of fracture. Comorbidities included 33 unique medical conditions of the Charlson or Elixhauser comorbidity index. We modelled the contribution of specific fractures on the risk of subsequent admissions or death within the following 2 years. There were 212,498 women and 95,372 men with fracture followed by 30,677 and 19,519 deaths, respectively over 163,482 and 384,995 person-years of follow up. Mean age at fracture was 72± 11 for women and 75± 11 for men. Proximal fractures including hip, femur, pelvis, rib, clavicle and humerus had increased mortality compared with their matched non-fracture counterparts with HRs ranging from 1.5-4.0, while distal fractures such as ankle, forearm, hand or foot fractures had similar or lower mortality risk. Almost 75% of men and 60% of women had ≥1 comorbidity. For every additional comorbidity, risk of mortality increased for all fracture types. However, only for proximal fractures did the fracture itself independently increase mortality risk over and above co-morbidity status. The 2-yr post fracture admission and mortality patterns diffe...
Tran, T, Bliuc, D, Pham, HM, van Geel, T, Adachi, JD, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, Josse, RG, Kaiser, SM, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV & Center, JR 2020, 'A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly', Journal of Bone and Mineral Research, vol. 35, no. 10, pp. 1923-1934.
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ABSTRACT Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7–15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of −1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, f...
Tran, Y, Craig, A, Craig, R, Chai, R & Nguyen, H 2020, 'The influence of mental fatigue on brain activity: Evidence from a systematic review with meta‐analyses', Psychophysiology, vol. 57, no. 5.
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AbstractThe occurrence of mental fatigue during tasks like driving a vehicle increases risk of injury or death. Changes in electroencephalographic (EEG) activity associated with mental fatigue has been frequently studied and considered a promising biomarker of mental fatigue. This is despite differences in methodologies and outcomes in prior research. A systematic review with meta‐analyses was conducted to establish the influence of mental fatigue on EEG activity spectral bands, and to determine in which regions fatigue‐related EEG spectral changes are likely to occur. A high‐yield search strategy identified 21 studies meeting inclusion criteria for investigating the change in EEG spectral activity in non‐diseased adults engaged in mentally fatiguing tasks. A medium effect size (using Cohen's g) of 0.68 (95%CI: 0.24–1.13) was found for increase in overall EEG activity following mental fatigue. Further examination of individual EEG spectral bands and regions using network meta‐analyses indicated large increases in theta (g = 1.03; 95%CI: 0.79–1.60) and alpha bands (g = 0.85; 95%CI: 0.47–1.43), with small to moderate changes found in delta and beta bands. Central regions of the scalp showed largest change (g = 0.80; 95%CI: 0.46–1.21). Sub‐group analyses indicated large increases in theta activity in frontal, central and posterior sites (all g > 1), with moderate changes in alpha activity in central and posterior sites. Findings have implications for fatigue monitoring and countermeasures with support for change in theta activity in frontal, central and posterior sites as a robust biomarker of mental fatigue and change in alpha wave activity considered a second line biomarker to account for individual variability.
Ulapane, N, Thiyagarajan, K, Hunt, D & Valls Miro, J 2020, 'Quantifying the Relative Thickness of Conductive Ferromagnetic Materials Using Detector Coil-Based Pulsed Eddy Current Sensors', Journal of Visualized Experiments, vol. 155, no. 155.
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Thickness quantification of conductive ferromagnetic materials by means of non-destructive evaluation (NDE) is a crucial component of structural health monitoring of infrastructure, especially for assessing the condition of large diameter conductive ferromagnetic pipes found in the energy, water, oil, and gas sectors. Pulsed eddy current (PEC) sensing, especially detector coil-based PEC sensor architecture, has established itself over the years as an effective means for serving this purpose. Approaches for designing PEC sensors as well as processing signals have been presented in previous works. In recent years, the use of the decay rate of the detector coil-based time domain PEC signal for the purpose of thickness quantification has been studied. Such works have established that the decay rate-based method holds generality to the detector coil-based sensor architecture, with a degree of immunity to factors such as sensor shape and size, number of coil turns, and excitation current. Moreover, this method has shown its effectiveness in NDE of large pipes made of grey cast iron. Following such literature, the focus of this work is explicitly PEC sensor detector coil voltage decay rate-based conductive ferromagnetic material thickness quantification. However, the challenge faced by this method is the difficulty of calibration, especially when it comes to applications such as in situ pipe condition assessment since measuring electrical and magnetic properties of certain pipe materials or obtaining calibration samples is difficult in practice. Motivated by that challenge, in contrast to estimating actual thickness as done by some previous works, this work presents a protocol for using the decay rate-based method to quantify relative thickness (i.e., thickness of a particular location with respect to a maximum thickness), without the requirement for calibration.
van Gelder, T, Mulhern, B, Schoormans, D, Husson, O & De Abreu Lourenço, R 2020, 'Assessing health-related quality of life in cancer survivors: factors impacting on EORTC QLU-C10D-derived utility values', Quality of Life Research, vol. 29, no. 6, pp. 1483-1494.
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PURPOSE:To investigate the factors influencing EORTC QLQ-C30-derived EORTC QLU-C10D utility values across five cancer types (non-Hodgkin lymphoma, multiple myeloma, colorectal, thyroid, and prostate cancer) and a general population sample. METHODS:Data from the Dutch population-based patient-reported outcomes following initial treatment and long-term evaluation of survivorship (PROFILES) registry collected between 2009 and 2012 were used. EORTC QLQ-C30 data were used to estimate utility values by applying the EORTC QLU-C10D instrument using Australian utility weights. Regression analyses were conducted, within and across cancer type, to examine the factors influencing utility values, including patient- and cancer-specific factors, as well as the EORTC QLQ-C30 scale/item scores. RESULTS:The mean utility value for the total cancer sample was 0.791 (SD 0.201), significantly lower than that from the general population (0.865, SD 0.165). Multiple myeloma patients had the lowest utility value at 0.663 (SD 0.244). Physical functioning, pain and nausea and vomiting were the health-related quality of life (HRQoL) domains with the greatest impact on utility values; cognitive functioning and dyspnea had the lowest impact. Of the demographic and clinical factors, unemployment for reasons other than retirement, age older than 75 years, number of comorbidities, and experience of symptoms all had a statistically significant negative impact on utility values. CONCLUSIONS:This study is one of the first to apply the EORTC QLU-C10D to a heterogeneous group of cancer patients. Results can be used to more efficiently target care towards factors influencing HRQoL. Furthermore, it enhances our understanding of how the EORTC QLU-C10D performs across cancer types, supporting its use in cost-utility analyses.
van Gogh, MJ, Wallace, LK & Coutts, AJ 2020, 'Positional Demands and Physical Activity Profiles of Netball', Journal of Strength and Conditioning Research, vol. 34, no. 5, pp. 1422-1430.
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Abstract van Gogh, MJ, Wallace, LK, and Coutts, AJ. Positional demands and physical activity profiles of netball. J Strength Cond Res 34(5): 1422–1430, 2020—The aim of this study was to examine the activity profiles and physiological demands of netball. Eleven representative youth netball players participated in this study. Global positioning system, heart rate, and accelerometer data were collected during 8 competitive matches. Sport-specific skills were analyzed using notational methods. The main findings were that players traveled less distance during a match than previously reported. The center covered significantly greater distances than the other positions (p < 0.001). The goal shooter and goal keeper covered the least distance and endured lower accelerometer loads than other positions (p < 0.001). Very low levels of very high-speed running and sprint efforts were observed across all positions. The proportion of time spent in the high (>85% maximum heart rate [HRmax]) HR zone ranged from 7.0 to 62.6%, highlighting a high variation in cardiovascular demands between each position. The center and goal attack had the greatest cardiovascular demands spending significantly more time in the high (>85% HRmax) HR zone (p < 0.001). The goal shooter and goal keeper spent significantly more time in the low (<70% HRmax) HR zone (p < 0.001). Players in attacking positions were shown to pass/catch significantly more players than in defending positions (p < 0.001). Players in defending positions had higher number of deflections and intercepts compared with players in attacking positions (p < 0.001). These findings revea...
Vasilescu, SA, Bazaz, SR, Jin, D, Shimoni, O & Warkiani, ME 2020, '3D printing enables the rapid prototyping of modular microfluidic devices for particle conjugation', Applied Materials Today, vol. 20, pp. 100726-100726.
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© 2020 Elsevier Ltd Antibody micro/nano-particle conjugates have proven to be essential tools in many diagnostic and nanomedicine applications. However, their production with homogenous coating and in a continuous fashion remains a tedious, labor-intensive, and costly process. In this regard, 3D micromixer-based microfluidic devices offer significant advantages over existing methods, where manipulating the flow in three dimensions increases fluid contact area and surface disruption, facilitating efficient mixing. While conventional softlithography is capable of fabricating simple 2D micromixers, complications arise when processing 3D structures. In this paper, we report the direct fabrication of a 3D complex microchannel design using additive manufacturing for the continuous conjugation of antibodies onto particle surfaces. This method benefits from a reduction in cost and time (from days to hours), simplified fabrication process, and limited post-processing. The flexibility of direct 3D printing allows quick and easy tailoring of design features to facilitate the production of micro and nanoparticles conjugated with functional antibodies in a continuous mixing process. We demonstrate that the produced antibody-functionalized particles retain their functionality by a firm and specific interaction with antigen presenting cells. By connecting 3D printed micromixers across the conjugation process, we illustrate the role of 3D printed microchannels as modularized components. The 3D printing method we report enables a broad spectrum of researchers to produce complex microfluidic geometries within a short time frame.
Vaughan, N & Gabrys, B 2020, 'Scoring and assessment in medical VR training simulators with dynamic time series classification', Engineering Applications of Artificial Intelligence, vol. 94, pp. 103760-103760.
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© 2020 Elsevier Ltd This research proposes and evaluates scoring and assessment methods for Virtual Reality (VR) training simulators. VR simulators capture detailed n-dimensional human motion data which is useful for performance analysis. Custom made medical haptic VR training simulators were developed and used to record data from 271 trainees of multiple clinical experience levels. DTW Multivariate Prototyping (DTW-MP) is proposed. VR data was classified as Novice, Intermediate or Expert. Accuracy of algorithms applied for time-series classification were: dynamic time warping 1-nearest neighbor (DTW-1NN) 60%, nearest centroid SoftDTW classification 77.5%, Deep Learning: ResNet 85%, FCN 75%, CNN 72.5% and MCDCNN 28.5%. Expert VR data recordings can be used for guidance of novices. Assessment feedback can help trainees to improve skills and consistency. Motion analysis can identify different techniques used by individuals. Mistakes can be detected dynamically in real-time, raising alarms to prevent injuries.
Vettori, L, Sharma, P, Rnjak-Kovacina, J & Gentile, C 2020, '3D Bioprinting of Cardiovascular Tissues for In Vivo and In Vitro Applications Using Hybrid Hydrogels Containing Silk Fibroin: State of the Art and Challenges', Current Tissue Microenvironment Reports, vol. 1, no. 4, pp. 261-276.
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AbstractPurpose of Review3D bioprinting of cardiovascular tissues for in vitro and in vivo applications is currently investigated as a potential solution to better mimic the microenvironment typical of the human heart. However, optimal cell viability and tissue vascularization remain two of the main challenges in this regard. Silk fibroin (SF) as a natural biomaterial with unique features supports cell survival and tissue vascularization. This review aims to evaluate the potential of hydrogels containing SF in 3D bioprinting of cardiac tissue that better recapitulate the native cardiac microenvironment.Recent FindingsSF hydrogels spontaneously develop nanocrystals, which limit their use for 3D bioprinting applications. Nevertheless, the printability of SF is improved in hybrid hydrogels by mixing it with other natural polymers (such as alginate and gelatin). This is achieved by adding SF with other polymers or by crosslinking it by peroxidase catalysis (i.e., with alginate). Compared to only SF-based hydrogels, hybrid hydrogels provide a durable bioprinted construct with improved mechanical stability and biological properties. To date, studies using cardiac cells in bioprinted SF constructs are yet to be performed.SummaryMixing SF with other polymers in bioprinted hybrid hydrogels improves the printability and durability of 3D bioprinted tissues. Studies using these hydrogels with cardiac cells will be required to evaluate the biocompatibility of SF hybrid hydrogels and to establish their potential use for cardiovascular applications.
Violi, JP, Bishop, DP, Padula, MP, Steele, JR & Rodgers, KJ 2020, 'Considerations for amino acid analysis by liquid chromatography-tandem mass spectrometry: A tutorial review', TrAC Trends in Analytical Chemistry, vol. 131, pp. 116018-116018.
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© 2020 Elsevier B.V. Amino acids are present in a variety of matrices from biological fluids to plant and animal tissues. We discuss options for amino acid extraction, sample clean-up and protein hydrolysis. Chromatographic separation of native amino acids is difficult due to their structure and physiochemical properties. Most analysts derivatise amino acids prior to analysis which improves the signal-to-noise ratio, provides more efficient ionisation and allows the use of reverse phase chromatography. Since chiral analysis is becoming increasingly important, we discuss chiral column chromatography and the use of chiral derivatisation agents. The choice of detector and parameters is based on a wide array of criteria including whether amino acids are native or derivatised and if targeted or untargeted analysis is being performed. This tutorial review aims to act as both a guide and to provide an overview of the techniques scientists currently employ for the analysis of amino acids via liquid chromatography-tandem mass spectrometry.
Virdun, C, Luckett, T, Davidson, PM & Phillips, J 2020, 'Strengthening palliative care in the hospital setting: a codesign study', BMJ Supportive & Palliative Care, pp. bmjspcare-2020.
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ObjectiveTo identify actions required to strengthen the delivery of person and family centred hospital-based palliative care so that it addressed the domains of care identified as important for inpatients with palliative care needs and their families.MethodsA codesign study involving a workshop with palliative care and acute hospital policy, consumer and clinical representatives in Australia. A modified nominal group process generated a series of actions, which were thematically analysed and refined, before being circulated to participants to gain consensus.ResultsMore than half (n=30, 58%) of the invited representatives (n=52) participated in the codesign process. Nine actions were identified as required to strengthen inpatient palliative care provision being: (a) evidence-informed practice and national benchmarking; (b) funding reforms; (c) securing executive level support; (d) mandatory clinical and ancillary education; (e) fostering greater community awareness; (f) policy reviews of care of the dying; (g) better integration of advance care planning; (h) strengthen nursing leadership; and (i) develop communities of practice for improving palliative care.ConclusionsChanges to policy, practice, education and further research are required to optimise palliative care within hospital settings, in accordance with the domains inpatients with palliative care needs and their families consider to be important. Achieving these changes will require a whole of sector approach and significant national and jurisdictional leadership.
Virdun, C, Luckett, T, Lorenz, K, Davidson, PM & Phillips, J 2020, 'Hospital patients’ perspectives on what is essential to enable optimal palliative care: A qualitative study', Palliative Medicine, vol. 34, no. 10, pp. 1402-1415.
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Background: The majority of expected deaths in high income countries occur in hospital where optimal palliative care cannot be assured. In addition, a large number of patients with palliative care needs receive inpatient care in their last year of life. International research has identified domains of inpatient care that patients and carers perceive to be important, but concrete examples of how these might be operationalised are scarce, and few studies conducted in the southern hemisphere. Aim: To seek the perspectives of Australian patients living with palliative care needs about their recent hospitalisation experiences to determine the relevance of domains noted internationally to be important for optimal inpatient palliative care and how these can be operationalised. Design: An exploratory qualitative study using semi-structured interviews. Setting/participants: Participants were recruited through five hospitals in New South Wales, Australia. Results: Twenty-one participants took part. Results confirmed and added depth of understanding to domains previously identified as important for optimal hospital palliative care, including: Effective communication and shared decision making; Expert care; Adequate environment for care; Family involvement in care provision; Financial affairs; Maintenance of sense of self/identity; Minimising burden; Respectful and compassionate care; Trust and confidence in clinicians and Maintenance of patient safety. Two additional domains were noted to be important: Nutritional needs; and Access to medical and nursing specialists. Conclusions: Taking a person-centred focus has...
Visser, M, Wong, S, Simonetti, S, Hazelton, JL, Devenney, E, Ahmed, RM, van Langenhove, T, Parker, D, Burrell, JR, Hodges, JR & Kumfor, F 2020, 'Using a second-person approach to identify disease-specific profiles of social behavior in frontotemporal dementia and Alzheimer's disease', Cortex, vol. 133, pp. 236-246.
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Changes in social behavior are recognized as potential symptoms of behavioral-variant frontotemporal dementia (bvFTD) and semantic dementia (SD), yet objective ways to assess these behaviors in natural social situations are lacking. This study takes a truly social (or second-person) approach and examines changes in real-world social behavior in different dementia syndromes, by analyzing non-scripted social interactions in bvFTD patients (n = 20) and SD patients (n = 20), compared to patients with Alzheimer's disease (AD) (n = 20). Video recordings of 10-min conversations between patients and behavioral neurologists were analyzed for the presence of socially engaging (e.g., nodding, smiling, gesturing) and disengaging behavior (e.g., avoiding eye contact, self-grooming, interrupting). Results demonstrated disease-specific profiles, with bvFTD patients showing less nodding and more looking away than AD, and SD patients showing more gesturing than AD. A principal components analysis revealed the presence of four unobserved components, showing atypical disengaging patterns of behavior. Whole-brain voxel-based morphometry analyses revealed distinct neurobiological bases for each of these components, with the brain regions identified previously associated with behavior selection, abstract mentalization and processing of multi-sensory and socially-relevant information, in mediating socially engaging and disengaging behavior. This study demonstrates the utility of systematic behavioral observation of social interactions in the differential diagnosis of dementia.
Vuckovic, S, Bryant, CE, Lau, KHA, Yang, S, Favaloro, J, McGuire, HM, Clark, G, de St. Groth, BF, Marsh-Wakefield, F, Nassif, N, Abadir, E, Vanguru, V, McCulloch, D, Brown, C, Larsen, S, Dunkley, S, Khoo, L, Gibson, J, Boyle, R, Joshua, D & Ho, PJ 2020, 'Inverse relationship between oligoclonal expanded CD69− TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients', Blood Advances, vol. 4, no. 19, pp. 4593-4604.
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Abstract CD8+CD57+ terminal effector T (TTE) cells are a component of marrow-infiltrating lymphocytes and may contribute to the altered immune responses in multiple myeloma (MM) patients. We analyzed TTE cells in the bone marrow (BM) and peripheral blood (PB) of age-matched controls and patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed (ND) MM using flow cytometry, mass cytometry, and FlowSOM clustering. TTE cells are heterogeneous in all subjects, with BM containing both CD69− and CD69+ subsets, while only CD69− cells are found in PB. Within the BM-TTE compartment, CD69− and CD69+ cells are found in comparable proportions in controls, while CD69− cells are dominant in MGUS and SMM and predominantly either CD69− or CD69+ cells in NDMM. A positive relationship between CD69+TTE and CD69−TTE cells is observed in the BM of controls, lost in MGUS, and converted to an inverse relationship in NDMM. CD69−TTE cells include multiple oligoclonal expansions of T-cell receptor/Vβ families shared between BM and PB of NDMM. Oligoclonal expanded CD69−TTE cells from the PB include myeloma-reactive cells capable of killing autologous CD38hi plasma cells in vitro, involving degranulation and high expression of perforin and granzyme. In contrast to CD69−TTE cells, oligoclonal expansions are not evident within CD69+TTE cells, which possess low perforin and granzyme expression and high inhibitory checkpoint expression and resemble T resident memory cells. Both CD69−TTE and CD69+TTE cells from the BM of NDMM produce large amounts of the inflammatory cytokines interferon-γ and tumor necrosis factor α. The balance between CD69− and CD69+ cells within the BM-TTE compartment may regulate immune responses in NDMM and contribute to the clinical heterogeneity of the disease.
Wang, B, Chan, YL, Zhou, S, Saad, S, Chen, H & Oliver, BG 2020, 'Offspring sex affects the susceptibility to maternal smoking-induced lung inflammation and the effect of maternal antioxidant supplementation in mice', Journal of Inflammation, vol. 17, no. 1.
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AbstractBackgroundCigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring. We have previously shown that maternal L-Carnitine treatment can reduce the adverse impacts of maternal SE on renal and brain disorders in offspring. Here, we investigated the effect of maternal L-Carnitine supplementation on lung inflammatory pathways, autophagy, and mitophagy markers in the offspring in response to maternal SE.MethodsFemale BALB/c mice (8 weeks) were exposed to cigarette smoke for 6 weeks prior to mating, during gestation and lactation. Some of the SE dams were given L-Carnitine supplementation (1.5 mM in drinking water, SE + LC) during gestation and lactation. Lungs from the offspring were studied at birth and adulthood (13 weeks).ResultsAt birth, in male offspring, there were increased levels of inflammatory markers (phosphorylated(p)-ERK1,2, p-P38 MAPK, p- NF-κB), and inflammasome marker (NLRP3), as well as mitophagy fission marker Drp-1 and autophagosome marker (LC3A/B-II) in the lung. Maternal L-Carnitine supplementation significantly reduced NLRP3 level. In contrast, maternal SE only increased IL1-β in female offspring, which was reversed by maternal L-Carnitine supplementation. At 13 weeks, there was an increase in LC3A/B-II and p- NF-κB in the male SE offspring with reduced p-JNK1,2, which were partially normalised by maternal L-Carnitine treatment. Female offspring were not affected by maternal SE at this age.ConclusionMaternal SE had adverse impacts on the male offspring’s lung, which were partially alleviated by maternal L-Carnitine supplementation. Females seem to be less affected by the adverse effects of m...
Wang, B, Chen, H, Chan, YL & Oliver, BG 2020, 'Is there an association between the level of ambient air pollution and COVID-19?', American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 319, no. 3, pp. L416-L421.
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Epidemiological studies suggest that environmental factors (e.g., air pollution) can influence the spread and infectivity of coronavirus disease 2019 (COVID-19); however, very few papers have investigated or discussed the mechanism behind the phenomenon. Given the fact that pollution will increase as social distancing rules are relaxed, we summarized the current understanding of how air pollution may affect COVID-19 transmission and discussed several possible mechanisms. Air pollution exposure can dysregulate the human immune response and make people more susceptible to infections, and affect infectivity. For example, in response to exposure to air pollution, angiotensin-converting enzyme 2 will increase, which is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This may increase the efficiency of viral infection. It is also possible that air pollution can facilitate SARS-CoV-2 spread by increasing the transmission, and potentially, SARS-CoV-2 can also survive longer when attached to a pollutant.
Wang, B, Chen, H, Chan, YL, Wang, G & Oliver, BG 2020, 'Why Do Intrauterine Exposure to Air Pollution and Cigarette Smoke Increase the Risk of Asthma?', Frontiers in Cell and Developmental Biology, vol. 8.
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© Copyright © 2020 Wang, Chen, Chan, Wang and Oliver. The prevalence of childhood asthma is increasing worldwide and increased in utero exposure to environmental toxicants may play a major role. As current asthma treatments are not curative, understanding the mechanisms underlying the etiology of asthma will allow better preventative strategies to be developed. This review focuses on the current understanding of how in utero exposure to environmental factors increases the risk of developing asthma in children. Epidemiological studies show that maternal smoking and particulate matter exposure during pregnancy are prominent risk factors for the development of childhood asthma. We discuss the changes in the developing fetus due to reduced oxygen and nutrient delivery affected by intrauterine environmental change. This leads to fetal underdevelopment and abnormal lung structure. Concurrently an altered immune response and aberrant epithelial and mesenchymal cellular function occur possibly due to epigenetic reprograming. The sequelae of these early life events are airway remodeling, airway hyperresponsiveness, and inflammation, the hallmark features of asthma. In summary, exposure to inhaled oxidants such as cigarette smoking or particulate matter increases the risk of childhood asthma and involves multiple mechanisms including impaired fetal lung development (structural changes), endocrine disorders, abnormal immune responses, and epigenetic modifications. These make it challenging to reduce the risk of asthma, but knowledge of the mechanisms can still help to develop personalized medicines.
Wang, H, Roche, CD & Gentile, C 2020, 'Omentum support for cardiac regeneration in ischaemic cardiomyopathy models: a systematic scoping review', European Journal of Cardio-Thoracic Surgery, vol. 58, no. 6, pp. 1118-1129.
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Abstract OBJECTIVES Preclinical in vivo studies using omental tissue as a biomaterial for myocardial regeneration are promising and have not previously been collated. We aimed to evaluate the effects of the omentum as a support for bioengineered tissue therapy for cardiac regeneration in vivo. METHODS A systematic scoping review was performed. Only English-language studies that used bioengineered cardio-regenerative tissue, omentum and ischaemic cardiomyopathy in vivo models were included. RESULTS We initially screened 1926 studies of which 17 were included in the final qualitative analysis. Among these, 11 were methodologically comparable and 6 were non-comparable. The use of the omentum improved the engraftment of bioengineered tissue by improving cell retention and reducing infarct size. Vascularization was also improved by the induction of angiogenesis in the transplanted tissue. Omentum-supported bioengineered grafts were associated with enhanced host reverse remodelling and improved haemodynamic measurements. CONCLUSIONS The omentum is a promising support for myocardial regenerative bioengineering in vivo. Future studies would benefit from more homogenous methodologies and reporting of outcomes to allow for direct comparison.
Wang, J, Li, Y, Zhao, P, Tian, Y, Liu, X, He, H, Jia, R, Oliver, BG & Li, J 2020, 'Exposure to Air Pollution Exacerbates Inflammation in Rats with Preexisting COPD', Mediators of Inflammation, vol. 2020, pp. 1-12.
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Particulate matter with an aerodynamic diameter equal or less than 2.5 micrometers (PM2.5) is associated with the development of chronic obstructive pulmonary disease (COPD). The mechanisms by which PM2.5 accelerates disease progression in COPD are poorly understood. In this study, we aimed to investigate the effect of PM2.5 on lung injury in rats with hallmark features of COPD. Cardinal features of human COPD were induced in a rat model by repeated cigarette smoke inhalation and bacterial infection for 8 weeks. Then, from week 9 to week 16, some of these rats with COPD were subjected to real-time concentrated atmospheric PM2.5. Lung function, pathology, inflammatory cytokines, oxidative stress, and mucus and collagen production were measured. As expected, the COPD rats had developed emphysema, inflammation, and deterioration in lung function. PM2.5 exposure resulted in greater lung function decline and histopathological changes, as reflected by increased Mucin (MUC) 5ac, MUC5b, Collagen I, Collagen III, and the profibrotic cytokine α-smooth muscle-actin (SMA), transforming growth factor- (TGF-) β1 in lung tissues. PM2.5 also aggravated inflammation, increasing neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF) and cytokines including Interleukin- (IL-) 1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-4. The likely mechanism is through oxidative stress as antioxidants levels were decreased, whereas oxidants were increased, indicating a detrimental shift in the oxidant-antioxidant balance. Altogether, these results suggest that PM2.5 exposure could promote the development of COPD by impairing lung function and exacerbating pulmonary injury, and the potential mechanisms are related to inflammatory response and oxidative stress.
Wang, Y, Tricou, C, Raghuraman, N, Akintola, T, Haycock, NR, Blasini, M, Phillips, J, Zhu, S & Colloca, L 2020, 'Modeling Learning Patterns to Predict Placebo Analgesic Effects in Healthy and Chronic Orofacial Pain Participants', Frontiers in Psychiatry, vol. 11, p. 39.
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Successfully predicting the susceptibility of individuals to placebo analgesics will aid in developing more effective pain medication and therapies, as well as aiding potential future clinical use of placebos. In pursuit of this goal, we analyzed healthy and chronic pain patients' patterns of responsiveness during conditioning rounds and their links to conditioned placebo analgesia and the mediating effect of expectation on those responses. We recruited 579 participants (380 healthy, 199 with temporomandibular disorder [TMD]) to participate in a laboratory placebo experiment. Individual pain sensitivity dictated the temperatures used for high- and low-pain stimuli, paired with red or green screens, respectively, and participants were told there would be an analgesic intervention paired with the green screens. Over two conditioning sessions and one testing session, participants rated the painfulness of each stimulus on a visual analogue scale from 0 to 100. During the testing phase, the same temperature was used for both red and green screens to assess responses to the placebo effect, which was defined as the difference between the average of the high-pain-cue stimuli and low-pain-cue stimuli. Delta scores, defined as each low-pain rating subtracted from its corresponding high-pain rating, served as a means of modeling patterns of conditioning strength and placebo responsiveness. Latent class analysis (LCA) was then conducted to classify the participants based on the trajectories of the delta values during the conditioning rounds. Classes characterized by persistently greater or increasing delta scores during conditioning displayed greater placebo analgesia during testing than those with persistently lower or decreasing delta scores. Furthermore, the identified groups' expectation of pain relief acted as a mediator for individual placebo analgesic effects. This study is the first to use LCA to discern the relationship between patterns of learning and the resultant...
White, S, Jacobs, C & Phillips, J 2020, 'Mainstreaming genetics and genomics: a systematic review of the barriers and facilitators for nurses and physicians in secondary and tertiary care', Genetics in Medicine, vol. 22, no. 7, pp. 1149-1155.
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PURPOSE:Genetic and genomic health information increasingly informs routine clinical care and treatment. This systematic review aimed to identify the barriers and facilitators to integrating genetics and genomics into nurses' and physicians' usual practice (mainstreaming). METHODS:A search of MEDLINE, EMBASE, CINAHL, and PsycINFO generated 7873 articles, of which 48 were included. Using narrative synthesis, barriers and facilitators were mapped to the Theoretical Domains Framework (TDF). RESULTS:Barriers were limitations to genetics knowledge and skill, low confidence initiating genetics discussions, lack of resources and guidelines, and concerns about discrimination and psychological harm. Facilitators were positive attitudes toward genetics, willingness to participate in discussions upon patient initiation, and intention to engage in genetics education. CONCLUSION:Nurses and physicians are largely underprepared to integrate genetic and genomic health information into routine clinical care. Ethical, legal, and psychological concerns surrounding genetic information can lead to avoidance of genetics discussions. The knowledge-practice gap could limit patients' and families' access to vital genetic information. Building the capacity of the current and next generation of nurses and physicians to integrate genetics and genomics into usual clinical practice is essential if opportunities afforded by precision medicine are to be fully realized.
Woldhuis, RR, de Vries, M, Timens, W, van den Berge, M, Demaria, M, Oliver, BGG, Heijink, IH & Brandsma, C-A 2020, 'Link between increased cellular senescence and extracellular matrix changes in COPD', American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 319, no. 1, pp. L48-L60.
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Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups ( n = 9–11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated β-galactosidase (SA-β-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress ( MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-β-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD.
Xiang, Y, Basirun, C, Chou, J, Warkiani, ME, Török, P, Wang, Y, Gao, S & Kabakova, IV 2020, 'Background-free fibre optic Brillouin probe for remote mapping of micromechanics', Biomedical Optics Express, vol. 11, no. 11, pp. 6687-6687.
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Brillouin spectroscopy is a century-old technique that has recently receivedrenewed interest, as modern instrumentation has transformed it into a powerfulcontactless and label-free probe of micromechanical properties for biomedicalapplications. In particular, to fully harness the non-contact andnon-destructive nature of Brillouin imaging, there is strong motivation todevelop a fibre-integrated device and extend the technology into the domain ofin vivo and in situ operation, such as for medical diagnostics. This workpresents the first demonstration of a fibre optic Brillouin probe that iscapable of mapping the mechanical properties of a tissue-mimicking phantom.This is achieved through combination of miniaturised optical design, advancedhollow-core fibre fabrication and high-resolution 3D printing. The protypeprobe is compact, background-free and possesses the highest collectionefficiency to date, thus provides the foundation of a fibre-based Brillouindevice for remote in situ measurements in challenging and otherwisedifficult-to-reach environments, for biomedical, material science andindustrial applications.
Xie, W, Regan, MM, Buyse, M, Halabi, S, Kantoff, PW, Sartor, O, Soule, H, Berry, D, Clarke, N, Collette, L, D’Amico, A, Lourenco, RDA, Dignam, J, Eisenberger, M, James, N, Fizazi, K, Gillessen, S, Loriot, Y, Mottet, N, Parulekar, W, Sandler, H, Spratt, DE, Sydes, MR, Tombal, B, Williams, S & Sweeney, CJ 2020, 'Event-Free Survival, a Prostate-Specific Antigen–Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation', Journal of Clinical Oncology, vol. 38, no. 26, pp. 3032-3041.
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PURPOSE Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)–based composite end point, may further expedite trial completion. METHODS EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate–ICECaP–database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ≥ 0.7. RESULTS Data for 10,350 patients were analyzed from 15 radiation therapy–based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall’s tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. CONCLUSION EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo...
Xie, W, Regan, MM, Buyse, M, Halabi, S, Kantoff, PW, Sartor, O, Soule, H, Berry, D, Clarke, N, Collette, L, D'Amico, A, Lourenco, RDA, Dignam, J, Eisenberger, M, James, N, Fizazi, K, Gillessen, S, Loriot, Y, Mottet, N, Parulekar, W, Sandler, H, Spratt, DE, Sydes, MR, Tombal, B, Williams, S & Sweeney, CJ 2020, 'Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation', JOURNAL OF CLINICAL ONCOLOGY, vol. 38, no. 26, pp. 3032-+.
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Xie, Z, Gao, G, Wang, H, Li, E, Yuan, Y, Xu, J, Zhang, Z, Wang, P, Fu, Y, Zeng, H, Song, J, Hölscher, C & Chen, H 2020, 'Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α', Biomedicine & Pharmacotherapy, vol. 127, pp. 110155-110155.
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Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro, and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.
Xu, X, Ling, M, Inglis, SC, Hickman, L & Parker, D 2020, 'Eating and healthy ageing: a longitudinal study on the association between food consumption, memory loss and its comorbidities', International Journal of Public Health, vol. 65, no. 5, pp. 571-582.
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OBJECTIVES:To explore the longitudinal association between food groups and memory loss and comorbid heart disease and diabetes (both Type 1 and 2) for people living in New South Wales, Australia. METHODS:We assessed 139,096 adults (aged 45 years and over) from the 45 and Up Study who completed both baseline (2006-2009) and follow-up (2012-2015) surveys. Mixed linear and generalized estimating equation models were used to examine the longitudinal associations. RESULTS:High consumption of fruit, vegetable and protein-rich food associated with lower odds of memory loss. High consumption of fruit and vegetables also associated with lower odds of comorbid heart disease (p ≤ 0.001). People who aged ≥ 80 years with low consumption of cereals had the highest odds of memory loss and comorbid heart disease than people in other age groups (p < 0.01). CONCLUSIONS:The results highlighted the longitudinal association of fruit and vegetable in relation to memory loss and comorbid heart disease. Age effects on cereals consumption which have an influence on memory loss and comorbid heart disease.
Xu, X, Parker, D, Chang, S, Liu, G, Hall, J, Anderson, D & Inglis, S 2020, '017 A Gendered Approach to Examine Cardiovascular Disease Modifiable Risk Changes Over the Life-Course for Middle-Aged and Older Australian Adults', Heart, Lung and Circulation, vol. 29, pp. S45-S45.
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Yang, T, Miro, JV, Lai, Q, Wang, Y & Xiong, R 2020, 'Cellular Decomposition for Nonrepetitive Coverage Task With Minimum Discontinuities', IEEE/ASME Transactions on Mechatronics, vol. 25, no. 4, pp. 1698-1708.
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A mechanism to derive nonrepetitive coverage path solutions with a proven minimal number of discontinuities is proposed in this work, with the aim to avoid unnecessary, costly end-effector lift-offs for manipulators. The problem is motivated by the automatic polishing of an object. Due to the nonbijective mapping between the workspace and the joint-space, a continuous coverage path in the workspace may easily be truncated in the joint-space, incurring undesirable end-effector lift-offs. Inversely, there may be multiple configuration choices to cover the same point of a coverage path through the solution of the inverse kinematics. The solution departs from the conventional local optimization of the coverage path shape in task space, or choosing appropriate but possibly disconnected configurations, to instead explicitly explore the least number of discontinuous motions through the analysis of the structure of valid configurations in joint-space. The two novel contributions of this article include proof that the least number of path discontinuities is predicated on the surrounding environment, independent from the choice of the actual coverage path; thus, has a minimum. In addition, an efficient finite cellular decomposition method to optimally divide the workspace into the minimum number of cells, each traversable without discontinuities by any arbitrary coverage path within. Extensive simulation examples and real-world results on a 5 DoF manipulator are presented to prove the validity of the proposed strategy in realistic settings.
Yong, DOC, Saker, SR, Chellappan, DK, Madheswaran, T, Panneerselvam, J, Choudhury, H, Pandey, M, Chan, YL, Collet, T, Gupta, G, Oliver, BG, Wark, P, Hansbro, N, Hsu, A, Hansbro, PM, Dua, K & Zeeshan, F 2020, 'Molecular and Immunological Mechanisms Underlying the Various Pharmacological Properties of the Potent Bioflavonoid, Rutin', Endocrine, Metabolic & Immune Disorders - Drug Targets, vol. 20, no. 10, pp. 1590-1596.
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The application of medicinal plants has captured the interest of researchers in recent timesdue to their potent therapeutic properties and a better safety profile. The prominent role of herbal productsin treating and preventing multiple diseases dates back to ancient history and most of the moderndrugs today originated from their significant sources owing to their ability to control multiple targetsvia different signalling pathways. Among them, flavonoids consist of a large group of polyphenols,which are well known for their various therapeutic benefits. Rutin is considered one of the attractivephytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacologicalactivities via various underlying molecular mechanisms. It is usually prescribed for variousdisease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, wehave discussed and highlighted the different molecular mechanisms attributed to the various pharmacologicalactivities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic.This review will be beneficial to herbal, biological and molecular scientists in understandingthe pharmacological relevance of rutin at the molecular level.
Yu, H, Ye, L, Guo, Y & Su, S 2020, 'An Innovative 9-Parameter Magnetic Calibration Method Using Local Magnetic Inclination and Calibrated Acceleration Value', IEEE Sensors Journal, vol. 20, no. 19, pp. 11275-11282.
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© 2001-2012 IEEE. In this paper, an innovative algorithm for Tri-Axial Magnetometers calibration based on the magnetic inclination is proposed. The proposed 'Inclination based Calibration method' uses the fact that the angle between the local gravity and magnetic field is invariant hence overcoming the limitations of most existing in-field calibration methods which require nonlinear optimization. This calibration algorithm is formulated as the solution to a linear least square problem. A commonly used 9-parameter model and its associated 12-observation Icosahedron experimental scheme were developed to evaluate its applicability to calibrated Tri-Axial Magnetometers based on measured acceleration and magnetic data. The results show that the algorithm can provide effective calibration results for the magnetic field in both simulation and experiments. In addition, the influence of accelerometers data applied in this algorithm is investigated by simulation and experiment to demonstrate the importance of accelerometers data accuracy. The acceleration value after effective calibration is demonstrated to make an improvement in the estimation results.
Yu, H, Zhang, Y, Ye, L, Alqudah, HM, Guo, K, Argha, A, Celler, BG, Song, R & Su, S 2020, 'Nonparametric Model Prediction for Intelligent Regulation of Human Cardiorespiratory System to Prescribed Exercise Medicine', IEEE Access, vol. 8, pp. 224621-224630.
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Yu, TT, Kuppusamy, R, Yasir, M, Hassan, MM, Alghalayini, A, Gadde, S, Deplazes, E, Cranfield, C, Willcox, MDP, Black, DS & Kumar, N 2020, 'Design, Synthesis and Biological Evaluation of Biphenylglyoxamide-Based Small Molecular Antimicrobial Peptide Mimics as Antibacterial Agents', International Journal of Molecular Sciences, vol. 21, no. 18, pp. 6789-6789.
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There has been an increasing interest in the development of antimicrobial peptides (AMPs) and their synthetic mimics as a novel class of antibiotics to overcome the rapid emergence of antibiotic resistance. Recently, phenylglyoxamide-based small molecular AMP mimics have been identified as potential leads to treat bacterial infections. In this study, a new series of biphenylglyoxamide-based small molecular AMP mimics were synthesised from the ring-opening reaction of N-sulfonylisatin bearing a biphenyl backbone with a diamine, followed by the conversion into tertiary ammonium chloride, quaternary ammonium iodide and guanidinium hydrochloride salts. Structure–activity relationship studies of the analogues identified the octanesulfonyl group as being essential for both Gram-positive and Gram-negative antibacterial activity, while the biphenyl backbone was important for Gram-negative antibacterial activity. The most potent analogue was identified to be chloro-substituted quaternary ammonium iodide salt 15c, which possesses antibacterial activity against both Gram-positive (MIC against Staphylococcus aureus = 8 μM) and Gram-negative bacteria (MIC against Escherichia coli = 16 μM, Pseudomonas aeruginosa = 63 μM) and disrupted 35% of pre-established S. aureus biofilms at 32 μM. Cytoplasmic membrane permeability and tethered bilayer lipid membranes (tBLMs) studies suggested that 15c acts as a bacterial membrane disruptor. In addition, in vitro toxicity studies showed that the potent compounds are non-toxic against human cells at therapeutic dosages.
Zakarya, R, Sapkota, A, Chan, YL, Shah, J, Saad, S, Bottle, SE, Oliver, BG, Gorrie, CA & Chen, H 2020, 'Nitroxides affect neurological deficits and lesion size induced by a rat model of traumatic brain injury', Nitric Oxide, vol. 97, pp. 57-65.
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© 2020 Elsevier Inc. Research has attributed tissue damage post-traumatic brain injury (TBI) to two-pronged effects, increased reactive oxygen species (ROS) and impairment of endogenous antioxidant defence systems, underpinned by manganese superoxide dismutase (MnSOD). Novel antioxidant nitroxides have been shown to mimic MnSOD to ameliorate oxidative stress related disorders. This study aimed to investigate the effects of two nitroxides, CTMIO and DCTEIO, on the neurological outcomes following moderate TBI in rats induced by a weight drop device. The rats were immediately treated with CTMIO and DCTEIO (40 mM in drinking water) post-injury for up to 2 weeks. The brains were histologically examined at 24 h and 6 weeks post injury. DCTEIO reduced the lesion size at both 24h and 6 weeks, with normalised performance in sensory, motor and cognitive tests at 24h post-injury. Astrogliosis was heightened by DCTEIO at 24h and still elevated at 6 weeks in this group. In TBI brains, cellular damage was evident as reflected by changes in markers of mitophagy and autophagy (increased fission marker dynamin-related protein (Drp)-1, and autophagy marker light chain 3 (LC3)A/B and reduced fusion marker optic atrophy (Opa)-1). These were normalised by DCTEIO treatment. CTMIO, on the other hand, seems to be toxic to the injured brains, by increasing injury size at 6 weeks. In conclusion, DCTEIO significantly improved tissue repair and preserved neurological function in rats with TBI possibly via a mitophagy mechanism. This study provides evidence for DCTEIO as a promising new option to alleviate lesion severity after moderate TBI, which is not actively treated.
Zhand, S, Razmjou, A, Azadi, S, Bazaz, SR, Shrestha, J, Jahromi, MAF & Warkiani, ME 2020, 'Metal–Organic Framework-Enhanced ELISA Platform for Ultrasensitive Detection of PD-L1', ACS Applied Bio Materials, vol. 3, no. 7, pp. 4148-4158.
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© 2020 American Chemical Society. The programmed cell death ligand 1 (PD-L1) protein has emerged as a predictive cancer biomarker and sensitivity to immune checkpoint blockade-based cancer immunotherapies. Current technologies for the detection of protein-based biomarkers, including the enzyme-linked immunosorbent assay (ELISA), have limitations such as low sensitivity and limit of detection (LOD) in addition to degradation of antibodies in exposure to environmental changes such as temperature and pH. To address these issues, we have proposed a metal-organic framework (MOF)-based ELISA for the detection of the PD-L1. A protective coating based on Zeolitic Imidazolate Framework 8 (ZIF-8) MOF thin film and polydopamine-polyethylenimine (PDA-PEI) was introduced on an ELISA plate for the improvement of antibody immobilization. Sensitivity and LOD of the resulting platform were compared with a conventional ELISA kit, and the bioactivity of the antibody in the proposed immunoassay was investigated in response to various pH and temperature values. The LOD and sensitivity of the MOF-based PD-L1 ELISA were 225 and 15.12 times higher, respectively, compared with those of the commercial ELISA kit. The antibody@ZIF-8/PDA-PEI was stable up to 55 °C and the pH range 5-10. The proposed platform can provide sensitive detection for target proteins, in addition to being resistant to elevated temperature and pH. The proposed MOF-based ELISA has significant potential for the clinical and diagnostic studies.
Zhang, S, Lin, M, Zou, X, Su, S, Zhang, W, Zhang, X & Guo, Z 2020, 'LSTM-based air quality predicted model for large cities in China', Nature Environment and Pollution Technology, vol. 19, no. 1, pp. 229-236.
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In this paper, the LSTM model is used to predict the PM2.5 concentrations in five representative Chinese cities with the GDP exceeding 1 trillion Yuan, including Beijing, Chengdu, Shanghai, Shenzhen and Wuhan. The PM2.5 concentration data in 2015-2017 are selected for training, and the results are optimized to achieve an efficient solution by adjusting the parameters. Based on the optimized solution, a test is carried out to predict the PM2.5 concentration in 2018, and the results are compared with the real value obtained from the monitoring centre. According to the comparison results, the correlation coefficient of Wuhan and Chengdu is 0.86724 and 0.80070, which are the highest in these five cities. While the correlation coefficient of Shenzhen and Shanghai, are 0.78225, 0.72147, Beijing, as the capital city of China achieved the lowest correlation coefficient which is 0.64118. The LSTM-based predictive model has relatively good reliability and transferability. More effective predictive results can be achieved by implementing deep learning to analyse PM2.5 concentration.
Zhang, W, Liu, T, Ueland, M, Forbes, SL, Wang, RX & Su, SW 2020, 'Design of an efficient electronic nose system for odour analysis and assessment', Measurement, vol. 165, pp. 108089-108089.
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© 2020 Elsevier Ltd This paper presents an efficient electronic nose (e-nose) system, named “NOS.E”, for odour analysis and assessment. In addition to the reliable hardware and software designs, an airflow intake system is implemented to ensure the precise odour analysis procedure in the NOS.E system. Additionally, a particular control logic was introduced to improve the test efficiency of the NOS.E by reducing operation time. Furthermore, the fault detection and alarming design can generate a high-reliability performance by constantly monitoring its working status. To evaluate the performance of the NOS.E, three types of alcohols were tested by the NOS.E and compared to data collected by comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS). The results indicate that the NOS.E can successfully distinguish three different alcohols with high efficiency and low cost and has the potential to be a universal odour analysis platform implemented in various applications.
Zhang, X, Zhao, Z, Zheng, Y & Li, J 2020, 'Prediction of Taxi Destinations Using a Novel Data Embedding Method and Ensemble Learning', IEEE Transactions on Intelligent Transportation Systems, vol. 21, no. 1, pp. 68-78.
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Zhao, Z, Zhang, X, Chen, F, Fang, L & Li, J 2020, 'Accurate prediction of DNA N4-methylcytosine sites via boost-learning various types of sequence features', BMC Genomics, vol. 21, no. 1, p. 627.
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AbstractBackgroundDNA N4-methylcytosine (4mC) is a critical epigenetic modification and has various roles in the restriction-modification system. Due to the high cost of experimental laboratory detection, computational methods using sequence characteristics and machine learning algorithms have been explored to identify 4mC sites from DNA sequences. However, state-of-the-art methods have limited performance because of the lack of effective sequence features and the ad hoc choice of learning algorithms to cope with this problem. This paper is aimed to propose new sequence feature space and a machine learning algorithm with feature selection scheme to address the problem.ResultsThe feature importance score distributions in datasets of six species are firstly reported and analyzed. Then the impact of the feature selection on model performance is evaluated by independent testing on benchmark datasets, where ACC and MCC measurements on the performance after feature selection increase by 2.3% to 9.7% and 0.05 to 0.19, respectively. The proposed method is compared with three state-of-the-art predictors using independent test and 10-fold cross-validations, and our method outperforms in all datasets, especially improving the ACC by 3.02% to 7.89% and MCC by 0.06 to 0.15 in the independent test. Two detailed case studies by the proposed method have confirmed the excellent overall performance and correctly identified 24 of 26 4mC sites from the C.elegans gene, and 126 out of 137 4mC sites from the D.melanogaster gene.ConclusionsThe results show that the proposed feature space and learning algorithm with feature selection can improve the performance of DNA 4mC prediction on the benchmark datasets. The two case studies prove the effectiveness of our method in practical...
Zheng, D, Zhang, H, Zhang, JA, Zheng, W & Su, SW 2020, 'Stability of asynchronous switched systems with sequence-based average dwell time approaches', Journal of the Franklin Institute, vol. 357, no. 4, pp. 2149-2166.
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© 2019 The Franklin Institute This paper studies the stability problem of asynchronous switched systems and proposes novel sequence-based average dwell time approaches. Both continuous-time and discrete-time systems are considered. The proposed approaches exploit the switching sequences of subsystems which were seldom utilized in the literature. More specifically, our approaches exploit the differences between different switching sequences, including the maximal asynchronous switching time, the energy changing degree at switching times, and the increasing speed of energy functions in asynchronous time intervals. As a result, the proposed approaches can reduce the threshold value of average dwell time significantly. We also propose an approach to counterbalance the increasing of energy functions in asynchronous time intervals by prolonging the preceding rather than subsequent subsystem. Numerical results demonstrate that the proposed approaches can improve the performance significantly in comparison with a well-known method.
Zheng, D, Zhang, JA, Zhang, H, Zheng, WX & Su, SW 2020, 'Consensus of Second-Order Multi-Agent Systems Without a Spanning Tree: A Sequence-Based Topology-Dependent Method', IEEE Access, vol. 8, pp. 162209-162217.
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Zheng, J, Li, J & Zheng, Y 2020, 'Guest Editorial for the 29th International Conference on Genome Informatics (GIW 2018)', IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 17, no. 3, pp. 726-727.
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