22 research outputs found

    ANCA-associated vasculitis.

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    The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients

    A Downscaling Approach Toward High-resolution Surface Mass Balance Over Antarctica

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    The Antarctic ice sheet surface mass balance shows high spatial variability over the coastal area. As state-of-the-art climate models usually require coarse resolutions to keep computational costs to a moderate level, they miss some local features that can be captured by field measurements. The downscaling approach adopted here consists of using a cascade of atmospheric models from large scale to meso-gamma scale. A regional climate model (Modegravele Atmospheacuterique Reacutegional) forced by meteorological reanalyses provides a diagnostic physically-based rain- and snowfall downscaling model with meteorological fields at the regional scale. Although the parameterizations invoked by the downscaling model are fairly simple, the knowledge of small-scale topography significantly improves the representation of spatial variability of precipitation and therefore that of the surface mass balance. Model evaluation is carried out with the help of shallow firn cores and snow height measurements provided by automatic weather stations. Although downscaling of blowing snow still needs to be implemented in the model, the net accumulation gradient across Law Dome summit is shown to be induced mostly by orographic effects on precipitation
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