49 research outputs found

    Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy

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    Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy and, in most patients, neurological decline. Death usually occurs in the second decade of life, although some patients with less severe disease have survived into their fifth or sixth decade. Until recently, there has been no effective therapy for MPS II, and care has been palliative. Enzyme replacement therapy (ERT) with recombinant human iduronate-2-sulphatase (idursulfase), however, has now been introduced. Weekly intravenous infusions of idursulfase have been shown to improve many of the signs and symptoms and overall wellbeing in patients with MPS II. This paper provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS II and provides recommendations for the use of ERT. The issue of treating very young patients and those with CNS involvement is also discussed. ERT with idursulfase has the potential to benefit many patients with MPS II, especially if started early in the course of the disease

    A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

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    dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

    Effects of dredging on the vegetation in a small lowland river

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    Background Conventional river engineering operations have a substantial influence on the fluvial ecosystem. Regulation and channelization generally reduce the physical heterogeneity of river beds and banks and the heterogeneity of habitats. They determine the character, diversity and species richness of plant communities. The effect of river regulation on vegetation has been repeatedly investigated, but few studies have been conducted within reaches of previously regulated rivers. The aim of this work is to expand and current knowledge about the impact of dredging on the vegetation of a regulated section of a lowland river. Materials & Methods The study included pre-dredging (1 year before) and post-dredging surveys (results 1 and 2 years after dredging). The vegetation was analysed in terms of species composition, origin of species, life forms, distribution of Grime’s life strategies, and selected ecological factors. The Shannon–Wiener biodiversity index (H) and evenness were also analysed in each year of the study. The impact of dredging on the vascular flora was assessed by ‘before-after-control-impact’ (BACI) analysis. Results The number of species and biodiversity as measured by the Shannon–Wiener index (H) increased in the analysed section of the river valley. However, enrichment of the flora was observed only on the floodplain, on the surface of the deposited dredging material, while the number of species in the river channel decreased, as dredging of the river bed and levelling of the banks had markedly reduced habitat diversity. Although species richness in the second year after the dredging approached the values recorded before the intervention, the absence of particularly species or phytocenoses associated with shallow river banks and sandbars was still observed. The change in habitat conditions and the destruction of the vegetation cover during the dredging enabled penetration by numerous previously unrecorded alien species of plants and apophytes. There was a perceptible increase in the role of therophytes in the flora. It is worth noting that the number of alien species and therophytes declined significantly in the second year after the dredging. Analysis of the proportions of species representing various life strategies showed that previously unrecorded species with the type R (ruderal) life strategy had appeared, representing by pioneer species occurring in frequently disturbed habitats. There was also a marked increase in the share of species representing the mixed C-R (competitive-ruderal) strategy, occurring in habitats with low levels of stress, whose competitive abilities are limited by repeated disturbances. By the second year after the dredging, however, these changes were largely no longer observed. Conclusions Through appropriate maintenance of the regulated river, it can be rapidly recolonized by vegetation after the procedure, but it may lead to the loss of some species and phytocoenoses

    Energy Levels of Light Nuclei. III

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    Knowledge webs and generative relations:: A network approach to developing competencies

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    Firms can enjoy competitive advantage by developing relations for building knowledge webs. In order to become valuable, the relations in these knowledge webs need to be of a 'generative character'. Our findings indicate that there are three different factors contributing to making relations in the web generative and thereby valuable. These three factors are (1) a balance between novelty and confirmation in knowledge exchanges, (2) complementarity of competencies, and (3) shared visions across organizational borders. We examine each of these potential factors for creating value in detail and also discuss how organizations can improve their ability to build generative relations.Knowledge Webs Knowledge Landscapes Generative Relations Resource-based View Network High Technology Competencies Wireless Communication 'Bluetooth'
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