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    Tethered membrane architectures - design and applications

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    This article was submitted to Colloidal Materials and Interfaces, a section of the journal Frontiers in Materials. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Membrane proteins perform a large number of essential biological tasks, but the understanding of these proteins has progressed much more slowly than that of globular proteins. The study of membrane proteins is hindered by the inherent complexity of the cellular membrane. Membrane proteins cannot be studied outside their native environment because their natural structure and function is compromised when the protein does not reside in the cellmembrane.Modelmembranes have been developed to provide a controlled, membrane-like environment in which these proteins can be studied in their native form and function without interference from other membrane components. Traditionally used model membranes such as bimolecular or black lipid membranes and floating lipid membranes suffer from several disadvantages including complex assembly protocols and limited stability. Furthermore, these membranes can only be studied with a narrow range of methodologies, severely restricting their use. To increase membrane stability, simplify the assembly process and increase the number of analytical tools that can be used to study the membranes, several strategies of covalently tethering the bilayer to its solid support have been developed. This review provides an overview of the methods used to assemble various membrane architectures, the properties of the resulting membranes and the tools used to study them

    Clustered domestic residential aged care in Australia: fewer hospitalisations and better quality of life

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    © Copyright 2018. The Medical Journal of Australia - Published version here reproduced with permission.Objective: To compare the outcomes and costs of clustered domestic and standard Australianmodels of residential aged care. Design: Cross-sectional retrospective analysis of linked health service data, January 2015 e February 2016. Setting: 17 aged care facilities in four Australian states providing clustered (four) or standard Australian (13) models of residential aged care. Participants: People with or without cognitive impairment residing in a residential aged care facility (RACF) for at least 12 months, not in palliative care, with a family member willing to participate on their behalf if required. 901 residents were eligible; 541 consented to participation (24% self-consent, 76% proxy consent). Main outcome measures: Quality of life (measured with EQ- 5D-5L); medical service use; health and residential care costs. Results: After adjusting for patient- and facility-level factors, individuals residing in clustered models of care had better quality of life (adjusted mean EQ-5D-5L score difference, 0.107; 95% CI, 0.028e0.186; P ¼ 0.008), lower hospitalisation rates (adjusted rate ratio, 0.32; 95% CI, 0.13e0.79; P ¼ 0.010), and lower emergency department presentation rates (adjusted rate ratio, 0.27; 95% CI, 0.14e0.53; P < 0.001) than residents of standard care facilities. Unadjusted facility running costs were similar for the two models, but, after adjusting for resident- and facilityrelated factors, it was estimated that overall there is a saving of 12962(2016values;9512 962 (2016 values; 95% CI, 11 092e14 831) per person per year in residential care costs. Conclusions: Clustered domestic models of residential care are associated with better quality of life and fewer hospitalisations for residents, without increasing whole of system costs.The INSPIRED study is supported by funding from the National Health and Medical Research Council (NHMRC) Partnership Centre on Dealing with Cognitive and Related Functional Decline in Older People (CDPC, GNT9100000). Australian aged care service providers are partners in the NHMRC CDPC; they provided information on the organisational structures of residential care and access to their facilities, but played no role in the analysis or interpretation of the study findings. Tiffany Easton is supported by a CDPC PhD Scholarship and an Australian Government Research Training Program Scholarship

    Fat mass, but not fat-free mass, predicts increased foot pain with obesity, independent of bariatric surgery

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    This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (June 2018) in accordance with the publisher’s archiving policyBackground Foot pain is a common manifestation of obesity. Objective To determine if bariatric surgery is associated with a reduction in foot pain and if body mass index (BMI) or body composition predict a change in foot pain. Setting University hospital. Methods Participants with foot pain awaiting bariatric surgery were recruited for this prospective study. Multivariable linear regression was used to determine predictors of change in foot pain between baseline and 6-month follow-up using body composition (fat mass index and fat-free mass index) or BMI, adjusting for, depression, age, sex, and group (surgery versus control). Results Forty-five participants (38 female), mean ± standard deviation age of 45.7 ± 9.4 years, were recruited for this study. Twenty-nine participants mean ± standard deviation BMI of 44.8 ± 7.0 kg underwent bariatric surgery, while 16 participants mean ± standard deviation BMI of 47.9 ± 5.2 kg were on the waiting list (control). One participant was lost to follow-up. The treatment group lost a mean of 24.3 kg (95% confidence interval [CI] 21.1–27.5), while the control group gained 1.2 kg (95% CI −2.5 to 4.9), respectively. In multivariable analysis, bariatric surgery was significantly associated with reduced foot pain at 6-month follow-up −32.6 points (95% CI −43.8 to −21.4, P < .001), while fat mass index was significantly associated with increased pain at follow-up 1.5 points (95% CI .2 to 2.8, P = .027), after controlling for fat-free mass index, age, sex, and depression. Conclusions Bariatric surgery was significantly associated with reduced foot pain. Higher baseline fat mass index, but not fat-free mass index or BMI, was predictive of increased foot pain at follow-up. Foot pain may be mediated by metabolic, rather than mechanical, factors in bariatric surgery candidates.TPW is funded by a Nursing and Allied Health Scholarship and Support Scheme funded by the Commonwealth Department of Health and administered by Services for Australian Rural and Remote Allied Health. This study was funded by a Project Grant from Arthritis Australia

    Data sharing from pharmaceutical industry sponsored clinical studies: audit of data availability

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Clinical trial transparency is important to participants, trialists, publishers, and regulators, and there have been recent major policy changes by the pharmaceutical industry regarding clinical study data sharing. However, it is unknown if these changes are enabling independent researchers to access participant-level data from prominent contemporary clinical trials sponsored by the pharmaceutical industry 2 years after publication of the primary results. Main text PubMed and ClinicalTrials.gov were searched to identify clinical trials of medicines sponsored by the pharmaceutical industry and first published between 1 July 2015 and 31 December 2015 in the top 10 general and internal medical journals by impact factor. For each clinical trial, the eligibility of independent researchers to request participant-level data was identified via the sponsor having a data sharing policy/process and a positive response to an enquiry. Fifty-six publications reporting on 61 industry-sponsored clinical trials were identified, of which 32 (52%) had a public data sharing policy/process and 9 (15%) were confirmed eligible for data sharing. Industry sponsors within the top 25 by global sales were more likely to have a data sharing policy (93% vs 10%), and there was a trend towards increased data sharing eligibility (23% vs 4%). Twenty-six studies were explicitly confirmed as ineligible for data sharing. The two most common data sharing policy conditions that prevented sharing of data for published results were the exclusion of studies that had ongoing follow-up of the published results and the exclusion of studies of medicines that have not yet achieved regulatory approval in the USA and the European Union. Conclusions Fifteen percent of the sampled clinical trials were available for data sharing 2 years after publication of primary results of the trial. Key issues limiting data sharing include a large proportion of industry sponsors who do not have a data sharing policy/process, and data sharing policy conditions that exclude access on the basis of ongoing follow-up and regulatory activity.This manuscript was produced with the financial and other support of Cancer Council SA’s Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health. Ashley Hopkins is a researcher funded by a postdoctoral fellowship from the National Breast Cancer Foundation, Australia

    How do diverse stakeholder groups perceive the activities of Non-Government Organisations working with disadvantaged children in Siem Reap, Cambodia.

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    This abstract was prepared for the inaugural 'HDR Student Conference', Flinders University, November 2018. Copyright © the authorThe focus of this presentation are the theories of social constructionism, postcolonialism and the social construction of the child and how these theoretical ideas are used to inform data collection and analysis in my thesis. Firstly, my thesis investigates key stakeholder groups affected by Non-Government Organisation work with disadvantaged children in Siem Reap, Cambodia. Social constructionism is drawn on to demonstrate how a relative positioning can aid the investigation of multiple groups engaged with the same phenomena of interest. Secondly, social constructionism and postcolonialism are proposed as acting as a lens to help identify aspects of Cambodian discourse that may reflect the impact of French colonialism and the Khmer Rouge. Specifically, postcolonialism critique of European constructions of the 'self' and 'other' will be used as a foundation for analysis of the data to look for similar socially constructed dualisms. These dualisms may include 'developed/undeveloped', 'humanitarian/sufferer' or in reference to the Khmer Rouge in an 'us/them' mentality. Finally, literature on the thesis topic is limited with regards to the voice of the child, with the majority of research focused on the adult's voice. The social construction of the child by James and Prout (2015) suggests that the child's voice in research should be more than a by-product of adult research as they are social actors with influence in their own right. As children are a focus of this study, the theory is used to help understand how children are constructed by the adult participants and how this may be used, along with the child voice, to help this cohort have a greater say in research and decision-making processes

    Food service satisfaction in aged care facilities: Development of a toolkit of instruments for the measurement of change

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    This abstract was prepared for the inaugural 'HDR Student Conference', Flinders University, November 2018. Copyright © the authorIntroduction: Although the average life span of Australian citizens is increasing, the final ten years may be accompanied by illness and disability thereby increasing the demand for residential aged care. Satisfaction with food service is a major factor in overall satisfaction and is important for the resident, resident's family, staff, cooks and management of the facility. There are currently limited valid and reliable tools available for measuring this construct and most tools investigate only the resident's perspective. As nursing homes are a complex system, a key gap is investigating other stakeholders that contribute to the food service setting as ultimately, this impacts the experience of the resident. Methods: Mixed method study underpinned by systems theory utilising qualitative interviews with stakeholders to develop quantitative instruments for measuring satisfaction. Transcripts will be analysed thematically to understand the factors (themes) relevant to stakeholders. Items for each questionnaire will be developed and content validity determined through an expert panel. Ethics approval has been obtained to recruit participants in nursing homes across Australia. Each instrument will undergo test/retesting and factor analysis will be conducted using SPSS to refine the tool. Implications: The development of a tool kit of instruments to measure change will enable residential aged care facilities to monitor quality improvement and detect areas of dissatisfaction within the food service system. Further, the revised Aged Care Quality Standards have a focus on stakeholder engagement and require homes to provide evidence of same, this tool kit will provide a valid and reliable way of ensuring this criteria is met

    Growth and metabolomic responses of Pacific white shrimp (Litopenaeus vannamei) to different dietary fatty acid sources and salinity levels

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    This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 24 month embargo from date of publication (Sept 2018) in accordance with the publisher’s archiving policyThe outstanding benefits of and strong interest in the inland low-salinity culture of penaeid shrimp have led to the growth of this industry worldwide. This study aimed to explore the effects of dietary fatty acids on shrimp in low-salinity culture. Individuals of the marine white shrimp Litopenaeus vannamei were fed one of three diets (coconut oil, fish oil, or an equal mixture of both) of differing fatty acid profiles for eight weeks while being maintained at two different salinities (3 or 30 psu). Then, a GC-TOF/MS-based metabolomics analysis was performed to reveal the regulatory roles of fatty acids in shrimp growth, survival and osmoregulation at two salinities. The shrimp fed the mixed oil diet had higher weight gain and survival, and those fed the diet with only fish oil added exhibited higher unsaturated fatty acid levels in the gills and hepatopancreas irrespective of salinity. Na+/K+-ATPase and total ATPase activities were lowest in the shrimp fed the mixed oil diet at both salinities. When coconut oil was the only lipid source, shrimp tissues contained higher tyrosine, lysine and serine levels at 3 psu than at 30 psu. In contrast, the shrimp fed fish oil as the sole lipid source had higher glucose at 3 psu than at 30 psu. This study indicates that appropriate supplementation of dietary unsaturated and saturated fatty acids can improve shrimp osmoregulation capacity and thus promote shrimp growth and survival in low-salinity water.This study was supported by a grant from the Hainan Provincial Natural Science Foundation of China (318MS008), the National Natural Science Foundation of China (No. 31472291) and the initial fund from Hainan University for R & D (KYQD(ZR)1736)

    “Just another piece of paperwork”: perceptions of clinicians on delirium screening following hip fracture repair elicited in focus groups

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    This article has been published in a revised form in International Psychogeriatrics, https://doi.org/10.1017/s1041610218001369. This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. Copyright © 2018 International Psychogeriatrics. This author accepted manuscript is made available following 6 month embargo from date of publication (October 2018) in accordance with the publisher’s copyright policyBackground: Delirium is a complex clinical syndrome characterized by disturbed consciousness, cognitive function, or perception and associated with serious adverse outcomes such as death, dementia, and the need for long-term care. However, recognition and management of delirium is poorly prioritized even though it is the most frequent complication among patients undergoing surgery following hip fracture. The aim of this study was to understand clinicians’ from orthopedic speciality perceptions in relation to recognition, diagnosis, and management of delirium. Methods: This was a qualitative study using in-depth focus groups discussions with clinical staff of one orthopedic unit within a level 1 trauma center, south of Adelaide, South Australia. Results: A total number of 17 individuals (14 nurses, 1 geriatric registrar, 1 nursing manager, and 1 speech therapist) participated in the focus groups. Four major themes were identified: (1) Delirium is important but can be hard to recognize and validate; (2) ambiguity on the use of delirium screening tool; (3) need of designated delirium care pathway; and (4) vital role of the family. Despite the initial lack of agreement on use of the objective tool to screen delirium, nurses did propose a number of ways that formal delirium screening could be included in routine nursing duties and existing nursing documentation. Conclusion: Although orthopedic nurses aim to provide effective care to patients experiencing delirium symptoms following hip fracture, they are doing so in the absence of structured screening, assessment, and multidisciplinary team approach. This study emphasizes the various barriers which need to be considered before attempting to change practice in this important area

    REM sleep fragmentation associated with depressive symptoms and genetic risk for depression in a community-based sample of adolescents

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    This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 12 month embargo from date of publication (November 2018) in accordance with the publisher’s archiving policy.Introduction Fragmented REM sleep may impede overnight resolution of distress and increase depressive symptoms. Furthermore, both fragmented REM and depressive symptoms may share a common genetic factor. We explored the associations between REM sleep fragmentation, depressive symptoms, and a polygenic risk score (PRS) for depression among adolescents. Methods About 161 adolescents (mean age 16.9 ± 0.1 years) from a birth cohort underwent a sleep EEG and completed the Beck Depression Inventory-II the same day. We calculated PRSes for depressive symptoms with PRSice 1.25 software using weights from a recent genome-wide association study for dimensions of depressive symptoms (negative emotion, lack of positive emotion and somatic complaints). REM fragmentation in relation to entire REM duration was manually calculated from all REM epochs. REM latency and density were derived using SomnoMedics DOMINO software. Results PRSes for somatic complaints and lack of positive emotions were associated with higher REM fragmentation percent. A higher level of depressive symptoms was associated with increased percent of REM fragmentation and higher REM density, independently of the genetic risks. Belonging to the highest decile in depressive symptoms was associated with a 2.9- and 7.6-fold risk of belonging to the highest tertile in REM fragmentation and density. In addition, higher PRS for somatic complaints had an independent, additive effect on increased REM fragmentation. Limitation A single night's sleep EEG was measured, thus the night-to-night stability of the REM fragmentation-depressive symptom link is unclear. Conclusion Depressive symptoms and genetic risk score for somatic complaints are independently associated with more fragmented REM sleep. This offers new insights on the quality of sleep and its relation to adolescents’ mood.The study was supported by the Academy of Finlan

    Cetuximab Alone or With Irinotecan for Resistant KRAS-, NRAS-, BRAF- and PIK3CA-wild-type Metastatic Colorectal Cancer: The AGITG Randomized Phase II ICECREAM Study

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    This manuscript version is made available under the CC-BYNC- ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 12 month embargo from date of publication (June 2018) in accordance with the publisher’s archiving policyBackground The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. Patients and Methods Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m2, then 250 mg/m2 cetuximab weekly, with or without irinotecan 180 mg/m2 every 2 weeks. The primary endpoint was 6-month progression-free survival; secondary endpoints were response rate, overall survival, toxicity, and quality of life. Results From 2012 to 2016, 48 patients were recruited. Two were ineligible, and 2 were not evaluable for response. Characteristics were balanced, except gender (male, 62% vs. 72%) and primary sidedness (left, 95% vs. 68%). For cetuximab compared with cetuximab-irinotecan, progression-free survival was 14% versus 41% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P = .008); response rate was 10% (2 partial responses) versus 38% (1 complete, 8 partial); P = .04. Grade 3 to 4 toxicities were less with cetuximab monotherapy (23% vs. 50%); global and specific quality of life scores did not differ. Conclusion In comparison with cetuximab alone, cetuximab plus irinotecan increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. This echoes data from molecularly unselected patients.This trial was sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG) and coordinated by the National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney. This work was supported by an unrestricted medical grant from Merck Serono Australia, an affiliate of Merck KGaA, Darmstadt, Germany, to the Australasian Gastro-Intestinal Trials Group (AGITG)

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