University General - Research Publications
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ItemThe psychometric properties and minimal clinically important difference for disability assessment using WHODAS 2.0 in critically ill patients(AUSTRALASIAN MED PUBL CO LTD, 2021-03)Objectives: The 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) provides a standardised method for measuring health and disability. This study aimed to determine its reliability, validity and responsiveness and to establish the minimum clinically important difference (MCID) in critically ill patients. Design: Prospective, multicentre cohort study. Setting: Intensive care units of six metropolitan hospitals. Participants: Adults mechanically ventilated for > 24 hours. Main outcome measures: Reliability was assessed by measuring internal consistency. Construct validity was assessed by comparing WHODAS 2.0 scores at 6 months with the EuroQoL visual analogue scale (EQ VAS) and Lawton Instrumental Activities of Daily Living (IADL) scale scores. Responsiveness was evaluated by assessing change over time, effect sizes, and percentage of patients showing no change. The MCID was calculated using both anchor and distribution-based methods with triangulation of results. Main results: A baseline and 6-month WHODAS 2.0 score were available for 448 patients. The WHODAS 2.0 demonstrated good correlation between items with no evidence of item redundancy. Cronbach α coefficient was 0.91 and average split-half coefficient was 0.91. There was a moderate correlation between the WHODAS 2.0 and the EQ VAS scores (r = -0.72; P < 0.001) and between the WHODAS 2.0 and the Lawton IADL scores (r = -0.66; P < 0.001) at 6 months. The effect sizes for change in the WHODAS 2.0 score from baseline to 3 months and from 3 to 6 months were low. Ceiling effects were not present and floor effects were present at baseline only. The final MCID estimate was 10%. Conclusion: The 12-item WHODAS 2.0 is a reliable, valid and responsive measure of disability in critically ill patients. A change in the total WHODAS 2.0 score of 10% represents the MCID.
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ItemNo Preview AvailableKnowledge, confidence, attitudes and beliefs of physiotherapists and physiotherapy students working with people with dementia: A mixed-methods systematic review(Wiley, 2021-12-01)BACKGROUND: Clinical care for people with dementia as a primary diagnosis, or as a co-morbidity, can be complex. Physiotherapists play a key role in the care of people living with dementia in multiple settings. The aim of this systematic review is to understand the attitudes, beliefs, knowledge and confidence of physiotherapists and physiotherapy students when working with people with dementia. METHOD: This was a mixed-methods systematic review that included qualitative and quantitative studies. Participants were physiotherapists working in any clinical specialty (e.g. gerontology, orthopaedic, neurological, cardio-respiratory), and physiotherapy students who had completed at least one clinical placement. If studies investigated physiotherapist and physiotherapy students' knowledge, confidence, attitudes or beliefs on working with a general population of older adults, they were excluded. The phenomena of interest and context were attitudes, beliefs, knowledge and confidence when working with people with dementia in any setting. Eleven databases were searched. Data synthesis followed a convergent integrated approach according to Joanna Briggs Institute methodology for mixed methods systematic reviews. RESULT: 15 studies were eligible for inclusion (9 quantitative and 6 qualitative studies). There were 5 key themes: rehabilitation potential (variable outcomes, poor potential), challenges in dementia care (communication, behaviour, cognition, risk, stress and burnout), education in dementia practice (inadequate training and knowledge, importance of experience), specialised area of practice (complexity of presentation, nuance of care, importance of time, holistic approach) and unsupportive systems (environment, time, risk aversion). One code, lack of desire to provide dementia care, did not contribute to any themes. CONCLUSION: Physiotherapists and physiotherapy students have low levels of knowledge and confidence in several areas important to working with people with dementia. With higher levels of knowledge and confidence associated with more positive attitudes and beliefs, dementia education needs of physiotherapists at all levels needs to be addressed.
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ItemNo Preview AvailableA multicentre point prevalence study of delirium assessment and management in patients admitted to Australian and New Zealand intensive care units(AUSTRALASIAN MED PUBL CO LTD, 2020-12)Objective: To characterise the assessment and management of delirium in patients admitted to intensive care units (ICUs) in Australia and New Zealand. Methods: We conducted a multicentre observational point prevalence study across 44 adult Australian and New Zealand ICUs. Data were extracted for all patients in the ICU in terms of assessment and treatment of delirium. ICU-level data were collected regarding the use of explicit protocols related to delirium. Results: We studied 627 patients, with 54% (336/627) having at least one delirium screening assessment performed. The Confusion Assessment Method for the ICU (CAM-ICU) was the most frequently used tool (88%, 296/336). Of patients assessed, 20% (68) were identified to have delirium. Eighteen per cent (111) of patients were administered a drug to manage delirium, with 41% (46) of those receiving a drug having no recorded assessment for delirium on that day. Of the drugs used to treat delirium, quetiapine was the most frequently administered. Physical restraints were applied to 8% (48/626) of patients, but only 17% (8/48) of such patients had been diagnosed with delirium. Most physically restrained patients either did not have delirium diagnosed (31%, 15/48) or had no formal assessment recorded (52%, 25/48) on that day. Conclusions: On the study day, more than 50% of patients had a delirium screening assessment performed, with 20% of screened patients deemed to have delirium. Drugs that are prescribed to treat delirium and physical restraints were frequently used in the absence of delirium or the formal assessment for its presence.
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ItemReplication: Belief elicitation with quadratic and binarized scoring rules(Elsevier, 2020-12-01)Researchers increasingly elicit beliefs to understand the underlying motivations of decision makers. Two commonly used methods are the quadratic scoring rule (QSR) and the binarized scoring rule (BSR). Hossain and Okui (2013) use a within-subject design to evaluate the performance of these two methods in an environment where subjects report probabilistic beliefs over binary outcomes with objective probabilities. In a near replication of their study, we show that their results continue to hold with a between-subject design. This is an important validation of the BSR given that researchers typically implement only one method to elicit beliefs. In favor of the BSR, reported beliefs are less accurate under the QSR than the BSR. Consistent with theoretical predictions, risk-averse subjects distort their reported beliefs under the QSR.
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ItemProteome reprogramming of endometrial epithelial cells by human trophectodermal small extracellular vesicles reveals key insights into embryo implantation(WILEY, 2021-07)Embryo implantation into the receptive endometrium is critical in pregnancy establishment, initially requiring reciprocal signalling between outer layer of the blastocyst (trophectoderm cells) and endometrial epithelium; however, factors regulating this crosstalk remain poorly understood. Although endometrial extracellular vesicles (EVs) are known to signal to the embryo during implantation, the role of embryo-derived EVs remains largely unknown. Here, we provide a comprehensive proteomic characterisation of a major class of EVs, termed small EVs (sEVs), released by human trophectoderm cells (Tsc-sEVs) and their capacity to reprogram protein landscape of endometrial epithelium in vitro. Highly purified Tsc-sEVs (30-200 nm, ALIX+ , TSG101+ , CD9/63/81+ ) were enriched in known players of implantation (LIFR, ICAM1, TAGLN2, WNT5A, FZD7, ROR2, PRICKLE2), antioxidant activity (SOD1, PRDX1/4/6), tissue integrity (EZR, RAC1, RHOA, TNC), and focal adhesions (FAK, ITGA2/V, ITGB1/3). Functionally, Tsc-sEVs were taken up by endometrial cells, altered transepithelial electrical resistance, and upregulated proteins implicated in embryo attachment (ITGA2/V, ITGB1/3), immune regulation (CD59, CD276, LGALS3), and antioxidant activity (GPX1/3/4, PRDX1/2/4/5/6): processes that are critical for successful implantation. Collectively, we provide critical insights into Tsc-sEV-mediated regulation of endometrial function that contributes to our understanding of the molecular basis of implantation.
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ItemImpact of chemically defined culture media formulations on extracellular vesicle production by amniotic epithelial cells(WILEY, 2021-07)The therapeutic properties of cell derived extracellular vesicles (EVs) make them promising cell-free alternative to regenerative medicine. However, clinical translation of this technology relies on the ability to manufacture EVs in a scalable, reproducible, and cGMP-compliant manner. To generate EVs in sufficient quantity, a critical step is the selection and development of culture media, where differences in formulation may influence the EV manufacturing process. In this study, we used human amniotic epithelial cells (hAECs) as a model system to explore the effect of different formulations of chemically defined, commercially sourced media on EV production. Here, we determined that cell viability and proliferation rate are not reliable quality indicators for EV manufacturing. The levels of tetraspanins and epitope makers of EVs were significantly impacted by culture media formulations. Mass spectrometry-based proteomic profiling revealed proteome composition of hAEC-EVs and the influence of media formulations on composition of EV proteome. This study has revealed critical aspects including cell viability and proliferation rate, EV yield, and tetraspanins, surface epitopes and proteome composition of EVs influenced by media formulations, and further insight into standardised EV production culture media that should be considered in clinical-grade scalable EV manufacture for generation of therapeutic EVs.
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ItemMental Health(WILEY, 2021-12)Abstract Mental health has been a focus of over 200 journal articles using the HILDA Survey data. This brief review provides an overview of the mental health data collected through the HILDA Survey, and discusses the potential reasons why HILDA Survey data have been used so frequently in mental health research. We reflect on how the HILDA Survey data have: provided insights into the profile of mental health in the Australian community, illustrated the importance of social ties for mental health and enabled investigation of social inequalities in mental health.
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ItemIncorporation of Vanadium and Molybdenum into Yttrium-Arsenotungstates Supported by Amino Acid Ligands(CSIRO PUBLISHING, 2020)The preference for incorporation of molybdenum over tungsten into specific sites of a family of yttrium-arsenotungstates with amino acid ligands prompted exploration of the incorporation of other metals, affording three new vanadium-containing (V/W and V/Mo/W) analogues: K2(GlyH)10[As4(V2W2)W44Y4O160(Gly)8(H2O)12]·11Gly (1), (MBAH)9(L-NleH)3[As4(V2W2)W44Y4O160(L-Nle)8(H2O)12] (2), and (MBAH)9(L-NleH)3[As4(V2W2)Mo2W42Y4O160(L-Nle)8(H2O)12] (3) (Gly=glycine and L-Nle=l-norleucine, MBAH=4-methylbenzylammonium). These hybrid polyoxometalates all possess a tetrametallic oxo-bridged {VIV2WVI2} central core surrounded by an amino acid-ligated cyclic metal-oxo framework. X-Ray photoelectron, UV-visible reflectance, and electron paramagnetic resonance spectroscopy, together with metal analysis, confirm the incorporation of vanadium into the polyoxometalates, while single crystal X-ray diffraction analysis supports the location of the vanadium atoms in the central core.
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ItemMetabolomes and Lipidomes of the Infective Stages of the Gastrointestinal nematodes, Nippostrongylus brasiliensis and Trichuris muris(MDPI, 2020-11)Soil-transmitted helminths, including hookworms and whipworms, infect billions of people worldwide. Their capacity to penetrate and migrate through their hosts' tissues is influenced by the suite of molecules produced by the infective developmental stages. To facilitate a better understanding of the immunobiology and pathogenicity of human hookworms and whipworms, we investigated the metabolomes of the infective stage of Nippostrongylus brasiliensis third-stage larvae (L3) which penetrate the skin and Trichuris muris eggs which are orally ingested, using untargeted liquid chromatography-mass spectrometry (LC-MS). We identified 55 polar metabolites through Metabolomics Standard Initiative level-1 (MSI-I) identification from N. brasiliensis and T. muris infective stages, out of which seven were unique to excretory/secretory products (ESPs) of N. brasiliensis L3. Amino acids were a principal constituent (33 amino acids). Additionally, we identified 350 putative lipids, out of which 28 (all known lipids) were unique to N. brasiliensis L3 somatic extract and four to T. muris embryonated egg somatic extract. Glycerophospholipids and glycerolipids were the major lipid groups. The catalogue of metabolites identified in this study shed light on the biology, and possible therapeutic and diagnostic targets for the treatment of these critical infectious pathogens. Moreover, with the growing body of literature on the therapeutic utility of helminth ESPs for treating inflammatory diseases, a role for metabolites is likely but has received little attention thus far.
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ItemExploring the Possible Cause of the Dramatic Increase in Measles Mortality During the 2015-2016 Mongolian Outbreak(OXFORD UNIV PRESS INC, 2021-10-01)