332 resultados para 1358
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The article first gives an introduction to well-being in school. Second, it argues for different perspectives to explore students’ well-being in the classroom, that is, a more general approach of well-being in school and a more specific approach of students’ individual well-being. Both views will be introduced and discussed in terms of their psychological and educational relevance. The empirical part of this article is based on a quantitative study including 2014 students of secondary I level schools1 and on a qualitative study consisting of 1358 emotional episodes reported by 58 adolescent students three times for two weeks. The results illustrate the potential of a multi-faceted approach to the affective aspects of school life by combining different views of student well-being.
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Aims To explore the impact of the functional severity of coronary artery stenosis on changes in myocardial oxygenation during pharmacological vasodilation, using oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging and invasive fractional flow reserve (FFR). An FFR is considered a standard of reference for assessing haemodynamic relevance of coronary artery stenosis; yet, the relationship of FFR to changes in myocardial oxygenation during vasodilator stress and thus to an objective marker for ischaemia on the tissue level is not well understood. Methods and results We prospectively recruited 64 patients with suspected/known coronary artery disease undergoing invasive angiography. The FFR was performed in intermediate coronary artery stenosis. OS-CMR images were acquired using a T2*-sensitive sequence before and after adenosine-induced vasodilation, with myocardial segments matched to angiography. Very strict image quality criteria were defined to ensure the validity of results. The FFR was performed in 37 patients. Because of the strict image quality criteria, 41% of segments had to be excluded, leaving 29/64 patients for the blinded OS-CMR analysis. Coronary territories with an associated FFR of <0.80 showed a lack of increase in myocardial oxygenation [mean signal intensity (ΔSI) −0.49%; 95% confidence interval (CI) −3.78 to 2.78 vs. +7.30%; 95% CI 4.08 to 10.64; P < 0.001]. An FFR of <0.54 best predicted a complete lack of a vasodilator-induced oxygenation increase (sensitivity 71% and specificity 75%). An OS-CMR ΔSI <4.78% identified an FFR of <0.8 with a sensitivity of 86% and specificity of 92%. Conclusion An FFR of <0.80 is associated with a lack of an adenosine-inducible increase in oxygenation of the dependent coronary territory, while a complete lack of such an increase was best predicted by an FFR of <0.54. Further studies are warranted to identify clinically meaningful cut-off values for FFR measurements and to assess the utility of OS-CMR as an alternative clinical tool for assessing the functional relevance of coronary artery stenosis.
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... ed. a Joanne Buxtorfio filio. Denuo ed. et annot. auxit Bernardus Fischerus
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Nitinol stent oversizing is frequently performed in peripheral arteries to ensure a desirable lumen gain. However, the clinical effect of mis-sizing remains controversial. The goal of this study was to provide a better understanding of the structural and hemodynamic effects of Nitinol stent oversizing. Five patient-specific numerical models of non-calcified popliteal arteries were developed to simulate the deployment of Nitinol stents with oversizing ratios ranging from 1.1 to 1.8. In addition to arterial biomechanics, computational fluid dynamics methods were adopted to simulate the physiological blood flow inside the stented arteries. Results showed that stent oversizing led to a limited increase in the acute lumen gain, albeit at the cost of a significant increase in arterial wall stresses. Furthermore, localized areas affected by low Wall Shear Stress increased with higher oversizing ratios. Stents were also negatively impacted by the procedure as their fatigue safety factors gradually decreased with oversizing. These adverse effects to both the artery walls and stents may create circumstances for restenosis. Although the ideal oversizing ratio is stent-specific, this study showed that Nitinol stent oversizing has a very small impact on the immediate lumen gain, which contradicts the clinical motivations of the procedure.
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BACKGROUND Physicians traditionally treat ulcerative colitis (UC) using a step-up approach. Given the paucity of data, we aimed to assess the cumulative probability of UC-related need for step-up therapy and to identify escalation-associated risk factors. METHODS Patients with UC enrolled into the Swiss IBD Cohort Study were analyzed. The following steps from the bottom to the top of the therapeutic pyramid were examined: (1) 5-aminosalicylic acid and/or rectal corticosteroids, (2) systemic corticosteroids, (3) immunomodulators (IM) (azathioprine, 6-mercaptopurine, methotrexate), (4) TNF antagonists, (5) calcineurin inhibitors, and (6) colectomy. RESULTS Data on 996 patients with UC with a median disease duration of 9 years were examined. The point estimates of cumulative use of different treatments at years 1, 5, 10, and 20 after UC diagnosis were 91%, 96%, 96%, and 97%, respectively, for 5-ASA and/or rectal corticosteroids, 63%, 69%, 72%, and 79%, respectively, for systemic corticosteroids, 43%, 57%, 59%, and 64%, respectively, for IM, 15%, 28%, and 35% (up to year 10 only), respectively, for TNF antagonists, 5%, 9%, 11%, and 12%, respectively, for calcineurin inhibitors, 1%, 5%, 9%, and 18%, respectively, for colectomy. The presence of extraintestinal manifestations and extended disease location (at least left-sided colitis) were identified as risk factors for step-up in therapy with systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and surgery. Cigarette smoking at diagnosis was protective against surgery. CONCLUSIONS The presence of extraintestinal manifestations, left-sided colitis, and extensive colitis/pancolitis at the time of diagnosis were associated with use of systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and colectomy during the disease course.
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AIM To identify morphologic factors affecting aortic expansion in patients with uncomplicated type B aortic dissections. METHODS Computed tomography data of 24 patients (18 male; median age: 61 years), diagnosed with acute uncomplicated type B aortic dissections between 2002 and 2013, were retrospectively reviewed. All patients had at least two computed tomography angiography scans and six months of uneventful follow-up. Computed tomography scans were assessed by two independent readers with regard to presence and number of entry tears. Thoracic and abdominal aortic diameters were derived using image processing software. RESULTS Twenty-two of 24 patients showed aortic expansion over a median computed tomography angiographic follow-up of 33.2 months. Annual rates showed an increase of 1.7 mm for total aortic diameter, 2.1 mm for the false and a decrease of -0.4 mm for the true lumen. In three patients (12.5%), aortic diameter exceeded 60 mm during follow-up, and all three patients underwent thoracic endovascular aortic repair. Patients with a maximum aortic diameter <4 cm at baseline showed a significantly higher expansion rate compared to cases with an initial maximum aortic diameter of ≥4 cm (p=0.0471). A median of two entries (range: 1-5) was recognized per patient. Presence of more than two entry tears (n = 13) was associated with faster overall diameter expansion (mean annual rates: 2.18 mm vs. 1.16 mm; p = 0.4556), and decrease of the cross-sectional surface of the true lumen over time (annual rate for > 2 entries vs. ≤2 entries: -7.8 mm(2) vs. +37.5 mm(2); p = 0.0369). Median size of entry tears was 12 mm (range: 2-53 mm). CONCLUSIONS The results presented herein suggest that uncomplicated type B aortic dissection patients with more than two entry tears and/or an initial maximum aortic diameter of<4 cm are at risk for aortic dilatation and, therefore, may require stricter follow-up including the possible need for early intervention.
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The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.
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This article aims at presenting an already existing research project. The Repertorium Academicum Germanicum (RAG) is supposed to be a "Who’s who" of the graduated and noble scholars of the late medieval Empire. It is designed to record biographical and social data of graduated theologians, jurists, physicians and Masters of Art as well as data of nobles from universities between 1250 and 1550. Furthermore, the project focuses on their examinations, networks, fields of activity in ecclesiastical and secular offices as well as their achievements and legacies (books, treatises, tombs etc). Right now, over 49.000 prosopographic entries are stored in the RAG database, partly available online (www.rag-online.org) and combined with digital maps (infographics), which already provide a basis for research in academic mobility determined by the top scholars of the time. In a next step, it should be possible to draw conclusions not only about personnel and knowledge transfer from university to society, its effects on political systems, daily life, the emergence of new occupational groups and professions, but also about cultural exchange within Europe.
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In the last two decades, trade liberalization under GATT/WTO has been partly offset by an increase in antidumping protection. Economists have argued convincingly that this is partly due to the inclusion of sales below cost in the definition of dumping during the GATT Tokyo Round. The introduction of the cost- based dumping definition gives regulating authorities a better opportunity to choose protection according to their liking. This paper investigates the domestic government's antidumping duty choice in an asymmetric information framework where the foreign firm's cost is observed by the domestic firm, but not by the government. To induce truthful revelation, the government can design a tariff schedule, contingent on firms' cost reports, accompanied by a threat to collect additional information for report verification (i.e., auditing) and, in case misreporting is detected, to set penalty duties. We show that depending on the concrete assumptions, the domestic government may not only be able to extract the true cost information, but also succeeds in implementing the full-information, governmental welfare-maximizing duty. In this case, the antidumping framework within GATT/WTO does not only offer the means to pursue strategic trade policy disguised as fair trade policy, but it also helps overcome the informational problems with regard to correctly determining the optimal strategic trade policy.
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Mit handschriftl. Anmerkungen von Emil Rödiger
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The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. Decreasing AC5 activity has been shown to have potential therapeutic benefit, including reduced stress on the heart, pain relief, and attenuation of morphine dependence and withdrawal behaviors. However, AC structure is well conserved, and there are currently no isoform selective AC inhibitors in clinical use. P-site inhibitors inhibit AC directly at the catalytic site, but with an uncompetitive or noncompetitive mechanism. Due to this mechanism and nanomolar potency in cell-free systems, attempts at ligand-based drug design of novel AC inhibitors frequently use P-site inhibitors as a starting template. One small molecule inhibitor designed through this process, NKY80, is described as an AC5 selective inhibitor with low micromolar potency in vitro. P-site inhibitors reveal important ligand binding “pockets” in the AC catalytic site, but specific interactions that give NKY80 selectivity are unclear. Identifying and characterizing unique interactions between NKY80 and AC isoforms would significantly aid the development of isoform selective AC inhibitors. I hypothesized that NKY80’s selective inhibition is conferred by AC isoform specific interactions with the compound within the catalytic site. A structure-based virtual screen of the AC catalytic site was used to identify novel small molecule AC inhibitors. Identified novel inhibitors are isoform selective, supporting the catalytic site as a region capable of more potent isoform selective inhibition. Although NKY80 is touted commercially as an AC5 selective inhibitor, its characterization suggests strong inhibition of both AC5 and the closely related AC6. NKY80 was also virtually docked to AC to determine how NKY80 binds to the catalytic site. My results show a difference between NKY80 binding and the conformation of classic P-site inhibitors. The selectivity and notable differences in NKY80 binding to the AC catalytic site suggest a catalytic subregion more flexible in AC5 and AC6 that can be targeted by selective small molecule inhibitors.
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Laminated lake sediments from the Dead Sea basin provide high-resolution records of climatic variability in the eastern Mediterranean region, which is especially sensitive to changing climatic conditions. In this study, we aim on detailed reconstruction of climatic fluctuations and related changes in the frequency of flood and dust deposition events at ca. 3300 and especially at 2800 cal. yr BP from high-resolution sediment records of the Dead Sea basin. A ca. 4-m-thick, mostly varved sediment section from the western margin of the Dead Sea (DSEn - Ein Gedi profile) was analysed and correlated to the new International Continental Scientific Drilling Program (ICDP) Dead Sea Deep Drilling Project core 5017-1 from the deep basin. To detect even single event layers, we applied a multi-proxy approach of high-resolution microscopic thin section analyses, micro-X-ray fluorescence (µ-XRF) element scanning and magnetic susceptibility measurements, supported by grain size data and palynological analyses. Based on radiocarbon and varve dating, two pronounced dry periods were detected at ~3500-3300 and ~3000-2400 cal. yr BP which are differently expressed in the sediment records. In the shallow-water core (DSEn), the older dry period is characterised by a thick sand deposit, whereas the sedimentological change at 2800 cal. yr BP is less pronounced and characterised mainly by an enhanced frequency of coarse detrital layers interpreted as erosion events. In the 5017-1 deep-basin core, both dry periods are depicted by halite deposits. The onset of the younger dry period coincides with the Homeric Grand Solar Minimum at ca. 2800 cal. yr BP. Our results suggest that during this period, the Dead Sea region experienced an overall dry climate, superimposed by an increased occurrence of flash floods caused by a change in synoptic weather patterns.