6,650 research outputs found

    Next steps for drowning prevention in rural and remote Australia: A systematic review of the literature

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    Objective: To examine unintentional drowning by remoteness in Australia. Design: A systematic review of both peer-reviewed and grey literature published between January 1990 and December 2019 (inclusive). Method: Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, MEDLINE (Ovid), PubMed, EMBASE, Scopus, PsycINFO (ProQuest), SPORTDiscus and Google Scholar were searched for studies exploring fatal and non-fatal unintentional drowning by remoteness. Epidemiological data, common factors and prevention strategies were extracted and mapped to Australian standard geographical classifications (major cities, inner regional, outer regional, remote and very remote). Level of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation and prevention strategies aligned to the hierarchy of control. Result: Thirty-two studies satisfied inclusion criteria (66% reporting epidemiology; 59% risk factors; and 44% prevention strategies). All (100%) included studies were assessed very low against Grading of Recommendations Assessment, Development and Evaluation. Findings indicate rural populations (ie, excluding major cities) have higher rates of drowning positively correlated with increasing remoteness. Common factors included age (child), natural water bodies, undertaking boating and watercraft activities and alcohol consumption. While a range of prevention strategies has been proposed, only one study outlined a rural drowning prevention strategy which had been implemented and evaluated. Strategies were generally low on the hierarchy of control. Conclusion: Rural populations are proportionately overrepresented in drowning statistics. Proposed prevention strategies have unknown efficacy. Greater research into rural drowning of Australians is needed especially exploring behavioural motivations, program delivery, cost-effectiveness and evaluation. Development and use of a standard definition for remoteness are recommended. Rural populations use water extensively; therefore, there is an urgent need to keep them safe

    Effects of vaccination with altered peptide ligand on chronic pain in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis

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    Neuropathic pain is a chronic symptom of multiple sclerosis (MS) and affects nearly half of all MS sufferers. A key instigator of this pain is the pro-inflammatory response in MS. We investigated the behavioural effects of immunisation with a mutant peptide of myelin basic protein (MBP), termed altered peptide ligand (APL), known to initiate immune deviation from a pro-inflammatory state to an anti-inflammatory response in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male and female Lewis rats were injected with vehicle control or with varying doses of 50 or 100 µg guinea pig MBP in combination with or without APL. APL-treated animals established significantly lower disease severity compared to encephalitogenic MBP-treated animals. Animals with EAE developed mechanical, but not thermal pain hypersensitivity. Mechanical pain sensitivities were either improved or normalised during periods of clinical disease in male and female APL-treated animals as compared to the encephalitogenic group. No significant changes to thermal latency were observed upon co-immunisation with APL. Together these data indicate that APL ameliorates disease states and selectively mediates an analgesic effect on EAE animals

    Using New Submillimetre Surveys to Identify the Evolutionary Status of High-z Galaxies

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    This paper describes a key submillimetre survey which we are currently conducting to address some of the outstanding questions in cosmology - how, at what epoch and over what period of time did massive galaxies form at high redshift? A summary of the technical feasibility of future submillimetre observations with new ground-based, airborne and satellite telescopes is also presented.Comment: 6 pages, 3 postscript figures, LaTex uses Kluwer book style file crckapb10.sty, to appear in "Observational Cosmology with the New Radio Surveys", 13-15 January 1997, Puerto de la Cruz, Tenerife, M.Bremer, N.Jackson, I.Perez-Fournon (eds.), Kluwe

    Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor-Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching.

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    We have assessed whether HLA immunogenicity as defined by differences in donor-recipient HLA amino-acid sequence (amino-acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor-recipient HLA mismatch to induce donor-specific antibody (DSA). HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02-2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02-1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA-DR and HLA-DQ DSA, but only EMS correlated with the risk of HLA-A and -B DSA development. Differences in donor-recipient HLA amino-acid sequence and physicochemical properties enable better assessment of the risk of HLA-specific sensitization than conventional HLA matching.This study was supported by the Cambridge NIHR Biomedical Research Centre and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or NHSBT . VK was supported by an Academy of Medical Sciences Grant and an Evelyn Trust Grant. DHM was supported by an RCSEng Research Fellowship.This is the author accepted manuscript. The final version is available from Wiley via https://doi.org/10.1111/ajt.13707

    MRL proteins cooperate with activated Ras in glia to drive distinct oncogenic outcomes

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    The Mig10/RIAM/Lpd (MRL) adapter protein Lpd regulates actin dynamics through interactions with Scar/WAVE and Ena/VASP proteins to promote the formation of cellular protrusions and to stimulate invasive migration. However, the ability of MRL proteins to interact with multiple actin regulators and to promote serum response factor (SRF) signalling has raised the question of whether MRL proteins employ alternative downstream mechanisms to drive oncogenic processes in a context-dependent manner. Here, using a Drosophila model, we show that overexpression of either human Lpd or its Drosophila orthologue Pico can promote growth and invasion of RasV12-induced cell tumours in the brain. Notably, effects were restricted to two populations of Repo-positive glial cells: an invasive population, characterized by JNK-dependent elevation of Mmp1 expression, and a hyperproliferative population lacking elevated JNK signalling. JNK activation was not triggered by reactive immune cell signalling, implicating the involvement of an intrinsic stress response. The ability to promote dissemination of RasV12-induced tumours was shared by a subset of actin regulators, including, most prominently, Chicadee/Profilin, which directly interacts with Pico, and, Mal, a cofactor for serum response factor that responds to changes in G:F actin dynamics. Suppression of Mal activity partially abrogated the ability of pico to promote invasion of RasV12 tumours. Furthermore, we found that larval glia are enriched for serum response factor expression, explaining the apparent sensitivity of glial cells to Pico/RasV12 overexpression. Taken together, our findings indicate that MRL proteins cooperate with oncogenic Ras to promote formation of glial tumours, and that, in this context, Mal/serum response factor activation is rate-limiting for tumour dissemination

    Breathlessness and sexual activity in older adults: The Australian Longitudinal Study of Ageing

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    © 2018 The Author(s). Sexual activity is important to older adults (65 +). Breathlessness affects about 25% of older adults but impact on sexual activity is unknown. We evaluated the relationships between breathlessness and sexual inactivity and self-reported health among older community-dwelling adults in the Australian Longitudinal Study of Ageing. Associations between self-reported breathlessness (hurrying on level ground or walking up a slight hill) at baseline, self-reported sexual activity, overall health and health compared to people of the same age were explored using logistic regression at baseline and 2 years, adjusted for potential confounders (age, sex, marital status, smoking status and co-morbidities). Of 798 participants (mean age 76.4 years [SD, 5.8] 65 to 103; 53% men, 73% married), 688 (86.2%) had 2-year follow-up data. People with breathlessness had higher prevalence and duration of sexual inactivity (77.7% vs. 65.6%; p < 0.001; 12 [IQR, 5-17] vs. 9.5 [IQR, 5-16] years; p = 0.043). Breathlessness was associated with more sexual inactivity, (adjusted OR 1.75; [95% CI] 1.24-2.45), worse health (adjusted OR 2.02; 1.53-2.67) and worse health compared to peers (adjusted OR 1.72; 1.25-2.38). Baseline breathlessness did not predict more sexual inactivity at 2 years. In conclusion, breathlessness contributes to sexual inactivity and worse perceived health in older adults, which calls for improved assessment and management
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