ANCA-associated vasculitis.

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

Conservation significance of intact forest landscapes in the Scandinavian Mountains Green Belt

Context: As forest harvesting remains high, there is a crucial need to assess the remaining large, contiguous and intact forests, regionally, nationally and globally. Objectives: Our objective was to analyze the spatial patterns and structural connectivity of intact and primary forests in northern Sweden with focus on the Scandinavian Mountain region; one of the few remaining large European intact forest landscapes. Methods: Over 22 million ha with 14.5 million ha boreal and subalpine forest and with data consisting of a 60-70 year retrospective sequence, we analyzed distribution, density and connectivity of forests that have not been clear cut, using moving window and landscape analyzes derived from Circuitscape. Results: We revealed a contiguous, connected and semi-connected intact forest landscape forming a distinct Green Belt south to north along the mountain range. Almost 60% of the forestland remains intact, including contiguous clusters 10,000 ha and larger. The connectivity is particularly high in protected areas with primary forests outside contributing substantially to overall connectivity. We found gaps in connectivity in the southern parts, and furthermore low or absent connectivity across the whole inland and coastal areas of northern Sweden. Conclusions: Given its ecological values, the Scandinavian Mountains Green Belt is a key entity supporting ecological legacies, boreal biodiversity and ecosystem services, resilience and adaptive capacity, which needs to be safeguarded for the future. On the very large areas outside the mountain region, forestlands are severely fragmented, connectivity values are lost, and forest landscape restoration is needed for conservation and functional green infrastructure.