183 research outputs found

    Umsetzung der deutschen Approbationsordnung 2002 im modularen Reformstudiengang Heidelberger Curriculum Medicinale (HeiCuMed)

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    Am 1.10.2003 trat die neue deutsche Approbationsordnung für Ärzte (ÄAppO) in Kraft. Das klinische Lehrangebot sollte dabei in 22 Fächern, 12 Querschnittsbereichen und 5 Blockpraktika angeboten werden. Bereits 1998 begann die medizinische Fakultät der Universität Heidelberg das medizinische Curriculum stärker praktisch und interdisziplinär auszurichten. Dieses neue Curriculum erhielt den Namen HeiCuMed (Heidelberger Curriculum Medicinale). Planung und Organisation von HeiCuMed erfolgte in Kooperation mit verschiedenen universitären und auswärtigen Partnern. Dieser Artikel befasst sich mit der Umsetzung der neuen ÄAppO in HeiCuMed. Dabei wird auch dargestellt, inwiefern in der Literatur beschriebene Prinzipien erfolgreicher Curriculumsreform im Reformprozess beachtet wurden. 09.12.2008 | Sören Huwendiek, M. Kadmon, J. Jünger, M. Kirschfink, H.M. Bosse & F. Resc

    Primary chronic cold agglutinin disease: An update on pathogenesis, clinical features and therapy

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    Chronic cold agglutinin disease (CAD) is a subgroup of autoimmune hemolytic anemia. Primary CAD has traditionally been defined by the absence of any underlying or associated disease. The results of therapy with corticosteroids, alkylating agents and interferon-a have been poor. Cold reactive immunoglobulins against erythrocyte surface antigens are essential to pathogenesis of CAD. These cold agglutinins are monoclonal, usually IgMÎş auto antibodies with heavy chain variable regions encoded by the VH4-34 gene segment. By flowcytometric and immunohistochemical assessments, a monoclonal CD20+Îş+B-lymphocyte population has been demonstrated in the bone marrow of 90% of the patients, and lymphoplasmacytic lymphoma is a frequent finding. Novel attempts at treatment for primary CAD have mostly been directed against the clonal B-lymphocytes. Phase 2 studies have shown that therapy with the chimeric anti-CD20 antibody rituximab produced partial response rates of more than 50% and occasional complete responses. Median response duration, however, was only 11 months. In this review, we discuss the clinical and pathogenetic features of primary CAD, emphasizing the more recent data on its close association with clonal lymphoproliferative bone marrow disorders and implications for therapy. We also review the management and outline some perspectives on new therapy modalities

    Ecological networks: Pursuing the shortest path, however narrow and crooked

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    International audienceRepresenting data as networks cuts across all sub-disciplines in ecology and evolutionary biology. Besides providing a compact representation of the interconnections between agents, network analysis allows the identification of especially important nodes, according to various metrics that often rely on the calculation of the shortest paths connecting any two nodes. While the interpretation of a shortest paths is straightforward in binary, unweighted networks, whenever weights are reported, the calculation could yield unexpected results. We analyzed 129 studies of ecological networks published in the last decade that use shortest paths, and discovered a methodological inaccuracy related to the edge weights used to calculate shortest paths (and related centrality measures), particularly in interaction networks. Specifically, 49% of the studies do not report sufficient information on the calculation to allow their replication, and 61% of the studies on weighted networks may contain errors in how shortest paths are calculated. Using toy models and empirical ecological data, we show how to transform the data prior to calculation and illustrate the pitfalls that need to be avoided. We conclude by proposing a five-point checklist to foster best-practices in the calculation and reporting of centrality measures in ecology and evolution studies. The last two decades have witnessed an exponential increase in the use of graph analysis in ecological and conservation studies (see refs. 1,2 for recent introductions to network theory in ecology and evolution). Networks (graphs) represent agents as nodes linked by edges representing pairwise relationships. For instance, a food web can be represented as a network of species (nodes) and their feeding relationships (edges) 3. Similarly, the spatial dynamics of a metapopulation can be analyzed by connecting the patches of suitable habitat (nodes) with edges measuring dispersal between patches 4. Data might either simply report the presence/absence of an edge (binary, unweighted networks), or provide a strength for each edge (weighted networks). In turn, these weights can represent a variety of ecologically-relevant quantities, depending on the system being described. For instance, edge weights can quantify interaction frequency (e.g., visitation networks 5), interaction strength (e.g., per-capita effect of one species on the growth rate of another 3), carbon-flow between trophic levels 6 , genetic similarity 7 , niche overlap (e.g., number of shared resources between two species 8), affinity 9 , dispersal probabilities (e.g., the rate at which individuals of a population move between patches 10), cost of dispersal between patches (e.g., resistance 11), etc. Despite such large variety of ecological network representations, a common task is the identification of nodes of high importance, such as keystone species in a food web, patches acting as stepping stones in a dispersal network , or genes with pleiotropic effects. The identification of important nodes is typically accomplished through centrality measures 5,12. Many centrality measures has been proposed, each probing complementary aspects of node-to-node relationships 13. For instance, Closeness centrality 14,15 highlights nodes that are "near" to all othe

    Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

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    The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention
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