77 research outputs found

    Broadening Responsibilities: Consideration Of The Potential To Broaden The Role Of Uniformed Fire Service Employees

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    What is this report about? This report, commissioned by the National Joint Council for Local Authority Fire and Rescue Services (NJC), aims to identify what impact, if any, firefighters can have on the delivery of emergency medical response and wider community health interventions in the UK. What are the overall conclusions? Appropriately trained and equipped firefighters co-responding1 to targeted, specific time critical medical events, such as cardiac arrest, can improve patient survival rates. The data also indicate that there is support from fire service staff – and a potential need from members of the public, particularly the elderly, isolated or vulnerable – to expand ‘wider work’. This includes winter warmth assessments, Safe and Well checks, community defibrillator training and client referrals when staff believe someone may have dementia, are vulnerable or even, for example, have substance dependencies such as an alcohol addiction. However, there is currently insufficient data to estimate the net benefit of this work

    Work Programme Evaluation : the participant experience report

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    This report brings together and summarises the key evidence available from the different strands of the Work Programme evaluation relating to the experience of participants. In particular, it presents analyses from two waves of a large scale longitudinal survey of participants and a multi-wave (partly cross-section, partly longitudinal) programme of in-depth qualitative fieldwork with participants. The evaluation tracks the Work Programme over several years from its launch in 2011

    Motor-dependent microtubule disassembly driven by tubulin tyrosination

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    In cells, stable microtubules (MTs) are covalently modified by a carboxypeptidase, which removes the C-terminal Tyr residue of α-tubulin. The significance of this selective detyrosination of MTs is not understood. In this study, we report that tubulin detyrosination in fibroblasts inhibits MT disassembly. This inhibition is relieved by overexpression of the depolymerizing motor mitotic centromere-associated kinesin (MCAK). Conversely, suppression of MCAK expression prevents disassembly of normal tyrosinated MTs in fibroblasts. Detyrosination of MTs suppresses the activity of MCAK in vitro, apparently as the result of a decreased affinity of the adenosine diphosphate (ADP)–inorganic phosphate- and ADP-bound forms of MCAK for the MT lattice. Detyrosination also impairs MT disassembly in neurons and inhibits the activity of the neuronal depolymerizing motor KIF2A in vitro. These results indicate that MT depolymerizing motors are directly inhibited by the detyrosination of tubulin, resulting in the stabilization of cellular MTs. Detyrosination of transiently stabilized MTs may give rise to persistent subpopulations of disassembly-resistant polymers to sustain subcellular cytoskeletal differentiation

    A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome

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    BACKGROUND:Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. METHODS:Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). RESULTS:Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively. CONCLUSIONS:Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
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