934 research outputs found

    A fish stinks from the head: Ethnic diversity, segregation, and the collapse of Yugoslavia

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    Demographic analysis clarifies political issues in the collapse of Yugoslavia. In most regions, 1961-1991, ethnic diversity (estimated by informational entropy) increased and segregation (estimated by Theil’s H) decreased. In a few regions there was a reversal in 1991 as migration flows or presentations of self perhaps changed in anticipation of war. The analysis strengthens refutations of the view that long standing ethnic hatreds were the root cause of the Yugoslav collapse and supports analyses that attribute collapse to general economic crisis, economic competition between regions, and failures at the peak of government.collapse of Yugoslavia, diversity, ethnic politics, ethnicity, segregation, Yugoslavia

    Adoption of biosimilar infliximab for rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel diseases in the EU5: A budget impact analysis using a Delphi panel

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    Introduction: Introducing biosimilar infliximab for the treatment in rheumatology (rheumatoid arthritis and ankylosing spondylitis) and inflammatory bowel disease (Crohn's disease and ulcerative colitis) may reduce treatment costs associated with biologics. This study aimed to investigate the budget impact of adopting biosimilar infliximab in five European countries, considering that the budget impact includes the adoption of biosimilar infliximab and the availability of biologic alternatives such as vedolizumab, biosimilar etanercept, biosimilar rituximab, and other relevant factors. Methods: An existing budget impact model was adapted to forecast the budget impact in the UK, Germany, France, Spain, and Italy. Epidemiological parameters were derived from published literature reviewed in July 2015. Current market shares of biologics were derived from Therapy Watch (2012/2013 data). Respondents in a Delphi panel, conducted in 2015 and consisting of several leading rheumatologists and gastroenterologists from different nationalities, were asked to forecast uptake of biosimilar infliximab and estimate the proportion of patients eligible for a particular type of biological treatment, including biosimilar infliximab. Scenario analyses assessed the influence of various factors, including price reductions, on the budget. Results: Uptake of biosimilar infliximab was particularly expected for naïve patients; switching patients that already received other biologics was not expected much. Market shares after 5 years of biosimilar infliximab were ~2% in rheumatology in all five countries and in gastroenterology ranged from 4% in France to over 30% in Italy. Except for France, budgets were expected to decrease for rheumatologic diseases. For gastroenterology, budgets were expected to decrease in Spain and Italy. Budgets were expected to increase substantially in the UK and Germany, due to the introduction of vedolizumab in the studied period. In France, budget was expected to slightly increase for ankylosing spondylitis, Crohn's Disease, and ulcerative collitis. Savings in budget were expected in all countries, for all diseases, when larger price discounts on biosimilar infliximab were used. Discussion and Conclusion: This study has shown that only when price reductions are large en

    Wolbachia-mediated antiviral protection in Drosophila larvae and adults following oral infection

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    Understanding viral dynamics in arthropods is of great importance when designing models to describe how viral spread can influence arthropod populations. The endosymbiotic bacterium Wolbachia spp., which is present in up to 40% of all insect species, has the ability to alter viral dynamics in both Drosophila spp. and mosquitoes, a feature that in mosquitoes may be utilized to limit spread of important arboviruses. To understand the potential effect of Wolbachia on viral dynamics in nature, it is important to consider the impact of natural routes of virus infection on Wolbachia antiviral effects. Using adult Drosophila strains, we show here that Drosophila-Wolbachia associations that have previously been shown to confer antiviral protection following systemic viral infection also confer protection against virus-induced mortality following oral exposure to Drosophila C virus in adults. Interestingly, a different pattern was observed when the same fly lines were challenged with the virus when still larvae. Analysis of the four Drosophila-Wolbachia associations that were protective in adults indicated that only the w1118-wMelPop association conferred protection in larvae following oral delivery of the virus. Analysis of Wolbachia density using quantitative PCR (qPCR) showed that a high Wolbachia density was congruent with antiviral protection in both adults and larvae. This study indicates that Wolbachia-mediated protection may vary between larval and adult stages of a given Wolbachia-host combination and that the variations in susceptibility by life stage correspond with Wolbachia density. The differences in the outcome of virus infection are likely to influence viral dynamics in Wolbachia-infected insect populations in nature and could also have important implications for the transmission of arboviruses in mosquito populations

    Making identity assurance and authentication strength work for federated infrastructures

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    In both higher Research and Education (R&E) as well as in research-/ e-infrastructures (in short: infrastructures), federated access and single sign-on by way of national federations, operated in most cases by NRENs, are used as a means to provide users with access to a variety of services. Whereas in national federations institutional accounts, e.g. provided by a university, are typically used to access services, many infrastructures also accept other sources of identity: provided by \u27\u27community identity providers\u27\u27, social identity providers, or governmental IDs. In order to assess and communicate the quality of identities being used and authentications being performed, so called Level of Assurance (LoA) frameworks are used. Because sophisticated LoA frameworks like NIST 800-63-3, Kantara IAF 1420 or eIDAS regulation are often considered too complex to be used in R&E scenarios, the REFEDS Assurance Suite, a more lightweight approach, has been developed. To select an appropriate assurance level, Service Providers need to weigh risks and potential harms in relation to the kind of service they offer. However, the management of risks is often implicitly assumed and little or no guidance to determine the appropriate assurance level is given. In this paper, first, common LoA frameworks and their relation to risk management are investigated. Following that, their components are compared against the REFEDS Assurance Suite using a graphical representation. The focus of this paper lies in providing guidance and best practices based on example scenarios for both Service Providers to request the appropriate REFEDS assurance level, as well as for Identity Provider operators on how to implement REFEDS assurance components

    Engineering Silicon Oxide by Argon Ion Implantation for High Performance Resistance Switching

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    We report that implanting argon ions into a film of uniform atomic layer deposition (ALD)-grown SiOx enables electroforming and switching within films that previously failed to electroform at voltages <15 V. We note an implantation dose dependence of electroforming success rate: electroforming can be eliminated when the dosage is high enough. Our devices are capable of multi-level switching during both set and reset operations, and multiple resistance states can be retained for more than 30,000 s under ambient conditions. High endurance of more than 7 million (7.9 × 106) cycles is achieved alongside low switching voltages (±1 V). Comparing SiOx fabricated by this approach with sputtered SiOx we find similar conduction mechanisms between the two materials. Our results show that intrinsic SiOx switching can be achieved with defects created solely by argon bombardment; in contrast to defects generated during deposition, implantation generated defects are potentially more controllable. In the future, noble ion implantation into silicon oxide may allow optimization of already excellent resistance switching devices

    ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus

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    ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus.BackgroundThe enormous contribution of renin-angiotensin system (RAS) interruption with ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers (ARB) in the treatment of diabetic nephropathy has led to interest in the factors involved in angiotensin II (Ang II) generation. In normal subjects, RAS interruption using an ARB produced a 50% greater renal plasma flow (RPF) rise than with an ACE inhibitor, suggesting a substantial contribution of non-ACE pathways. Moreover, immunohistochemistry studies in kidneys of overtly proteinuric diabetic subjects showed up-regulation of chymase, an alternative Ang II-generating enzyme. Our aim was to determine the degree to which the non-ACE pathways contribute to RAS activation in type 1 diabetes mellitus (DM).MethodsType 1DM patients (N = 37, 14 M/23 F; age 31 ± 2 years; DM duration 16 ± 1.7 years; HbA1c 7.7.0 ± 0.3%) were studied on a high-salt diet. They received captopril 25mg po one day and candesartan 16mg po the next day. RPF and glomerular filtration rate (GFR) were measured before and up to 4 hours after drug administration.ResultsBoth captopril and candesartan induced a significant rise in RPF (baseline vs. peak <0.0001 for both), and the rise was concordant for the 2 drugs (r = 0.77,P < 0.001). However, the RPF responses were not significantly different between the 2 drugs (captopril 72 ± 11mL/min/1.73m2, candesartan 75 ± 12,P = 0.841).ConclusionIn predominantly normoalbuminuric, normotensive type 1 DM, activation of the intrarenal RAS reflects a mechanism involving primarily the classic ACE pathway

    Role of IL‐17 in atopy—A systematic review

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    Purpose of Review: Atopy is defined as the genetic predisposition to react with type I allergic diseases such as food-, skin-, and respiratory allergies. Distinct molecular mechanisms have been described, including the known Th2 driven immune response. IL-17A (IL-17) is mainly produced by Th17 cells and belongs to the IL-17 family of cytokines, IL-17A to F. While IL-17 plays a major role in inflammatory and autoimmune disorders, more data was published in recent years elucidating the role of IL-17 in allergic diseases. The present study aimed to elaborate specifically the role of IL-17 in atopy. Methods: A systematic literature search was conducted in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, regarding IL-17 and atopy/allergic diseases. Results: In total, 31 novel publications could be identified (food allergy n = 3, allergic asthma n = 7, allergic rhinitis [AR] n = 10, atopic dermatitis [AD] n = 11). In all allergic diseases, the IL-17 pathway has been investigated. Serum IL-17 was elevated in all allergic diseases. In AR, serum and nasal IL-17 levels correlated with the severity of the disease. In food allergies, serum IL-17E was also elevated in children. In AD, there is a trend for higher IL-17 values in the serum and skin specimen, while it is more expressed in acute lesions. In allergic asthma, serum IL-17 levels were increased. In two studies, higher serum IL-17 levels were found in severe persistent asthmatic patients than in intermittent asthmatics or healthy controls. Only one therapeutic clinical study exists on allergic diseases (asthma patients) using a monoclonal antibody against the IL-17 receptor A. No clinical efficacy was found in the total study population, except for a subgroup of patients with (post-bronchodilator) high reversibility. Summary: The role of IL 17 in the pathogenesis of allergic diseases is evident, but the involvement of the Th17 cytokine in the pathophysiological pathway is not conclusively defined. IL-17 is most likely relevant and will be a clinical target in subgroups of patients. The current data indicates that IL-17 is elevated more often in acute and severe forms of allergic diseases
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