Lancet
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The provision of good quality and equitable end-of-life care is high on the public and political agenda. Hospice is second only to home in terms of preference for place of death and scores higher than any other setting for quality of care. However, hospices have been criticised for inequality of access with respect to age, diagnosis, and socioeconomic status. We aimed to describe the demographic characteristics associated with hospice death in England, and assessed how these characteristics have changed over time. ⋯ The GUIDE_Care project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme (project number 09/2000/58).
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Insulin resistance and hyperandrogenism are the cardinal features of polycystic ovary syndrome (PCOS). Women with insulin receptor (INSR) mutations develop severe hyperandrogenism secondary to hyperinsulinaemia. We hypothesised that insulin might drive adipose testosterone generation from androstenedione through aldoketoredutase type 3 (AKR1C3) in women with insulin resistance. Here we assessed the effect of insulin on AKR1C3 activity in vivo and in vitro. ⋯ Wellcome Trust.
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DNA damage response (DDR) defects, particularly TP53 and biallelic ataxia telangiectasia mutated (ATM) aberrations, are associated with genomic instability, clonal evolution, and chemoresistance in chronic lymphocytic leukaemia (CLL). Therapies capable of providing long-term disease control in CLL patients with DDR defects are lacking. Using AZD6738, a novel ATR inhibitor, we investigated ATR pathway inhibition as a synthetically lethal strategy for targeting CLL cells with these defects. ⋯ Leukaemia & Lymphoma Research.
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Non-melanoma skin cancer is the most common cancer worldwide, and cutaneous squamous cell carcinomas (SCCs) account for substantial morbidity and mortality because of their potential for metastasis. SCCs are surrounded by an immune cell infiltrate containing regulatory T cells (Tregs). The aim of this study was to characterise Tregs in SCCs and investigate whether increased Treg numbers in primary skin SCCs are associated with subsequent metastasis. ⋯ Wellcome Trust, National Institute for Health Research.
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The benefit of statins in the prevention of cardiovascular disease is well founded, derived from their lipid lowering and pleiotropic effects. The concept of lipoproteins as lipid transporters has evolved to encompass functions in coagulation, inflammation, and redox reactions due to their unique protein cargo. The aim of this study was to determine the effect of statin therapy on lipoproteins and their protein cargo by use of an unbiased bottom-up proteomics approach in people with hypercholesterolaemia. ⋯ British Heart Foundation.