883 resultados para Wachtel, Andrew B.: Making a nation, breaking a nation
Resumo:
annoncés aux amis de l'humanité par C., ami de B. Schottlaender et ... de [Israel] Jacobsohn
Resumo:
OBJECTIVE To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. RESULTS Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. SIGNIFICANCE This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Resumo:
The central assumption in the literature on collaborative networks and policy networks is that political outcomes are affected by a variety of state and nonstate actors. Some of these actors are more powerful than others and can therefore have a considerable effect on decision making. In this article, we seek to provide a structural and institutional explanation for these power differentials in policy networks and support the explanation with empirical evidence. We use a dyadic measure of influence reputation as a proxy for power, and posit that influence reputation over the political outcome is related to vertical integration into the political system by means of formal decision-making authority, and to horizontal integration by means of being well embedded into the policy network. Hence, we argue that actors are perceived as influential because of two complementary factors: (a) their institutional roles and (b) their structural positions in the policy network. Based on temporal and cross-sectional exponential random graph models, we compare five cases about climate, telecommunications, flood prevention, and toxic chemicals politics in Switzerland and Germany. The five networks cover national and local networks at different stages of the policy cycle. The results confirm that institutional and structural drivers seem to have a crucial impact on how an actor is perceived in decision making and implementation and, therefore, their ability to significantly shape outputs and service delivery.
Resumo:
historisch-kritisch nachgewiesen durch G. Fr. Daumer
Resumo:
Introduction Recruiting and retaining volunteers who are prepared to make a long-term commitment is a major problem for Swiss sports clubs. With the inclusion of external counselling for the change and systematisation of volunteer management, sports clubs have a possibility to develop and defuse problems in spite of existing barriers and gaps in knowledge. To what extent is external counselling for personnel problems effective? It is often observed that standardised counselling inputs lead to varying consequences for sports clubs. It can be assumed that external impulses are interpreted and transformed differently into the workings of the club. However, this cannot be solely attributed to the situational or structural conditions of the clubs. It is also important to consider the underlying decision-making processes of a club. According to Luhmann’s organisational sociological considerations (2000), organisations (sports clubs) have to be viewed as social systems consisting of (communicated) decisions. This means that organisations are continually reproduced by decision-making processes. All other (observable) factors such as an organisation’s goals, recruiting strategies, support schemes for volunteers etc., have to be seen as an outcome of the operation of prior organisational decisions. Therefore: How do decision-making processes in sports clubs work in the context of the implementation of external counselling? Theoretical Framework An examination of the actual situation in sports clubs shows that decisions frequently appear to be shaped by inconsistency, unexpected outcomes, and randomness (Amis & Slack, 2003). Therefore, it must be emphasised that these decisions cannot be analysed according to any rational decision-making model. Their specific structural characteristics only permit a limited degree of rationality – bounded rationality. Non-profit organisations in particular are shaped by a specific mode of decisionmaking that Cohen, March, and Olsen (1972) have called the “garbage can model”. As sport clubs can also be conceived as “organised anarchies”, this model seems to offer an appropriate approach to understanding their practices and analysing their decision-making processes. The key concept in the garbage can model is the assumption that decision-making processes in organisations consist of four “streams”: (a) problems, (b) actors, (c) decision-making opportunities, and (d) solutions. Method Before presenting the method of the analysis of the decision-making processes in sports clubs, the external counselling will be described. The basis of the counselling is generated by a sports clubs’ capability to change. Due to the specific structural characteristics and organisational principles, change processes in sports clubs often merge with barriers and restrictions. These need to be considered when developing counselling guidelines for a successful planning and realisation of change processes. Furthermore, important aspects of personnel management in sports clubs and especially volunteer management must be implied in order to elaborate key elements for the counselling to recruit new volunteers (e.g., approach, expectations). A counselling of four system-counselling workshops was conceptualised by considering these specific characteristics. The decision-making processes in the sports clubs were analysed during the counselling and the implementation process. A case study is designed with the appropriate methodological approach for such explorative research. The approach adopted for these single case analyses was oriented toward the research program of behavioural decision-making theory (garbage can model). This posits that in-depth insights into organisational decision-making processes can only be gained through relevant case studies of existing organisational situations (Skille, 2013). Before, during and after the intervention, questionnaires and guided interviews were conducted with the project teams of the twelve par-ticipating football clubs to assess the different components of the “streams” in the context of external counselling. These interviews have been analysed using content analysis following guidelines as for-mulated by Mayring (2010). Results The findings show that decision-making processes in football clubs occur differently in the context of external counselling. Different initial positions and problems are the triggers for these decision-making processes. Furthermore, the implementation of the solutions and the external counselling is highly dependent on the commitment of certain people as central players within the decision-mak-ing process. The importance of these relationships is confirmed by previous findings in regard to decision-making and change processes in sports clubs. The decision-making processes in sports clubs can be theoretically analysed using behavioural decision-making theory and the “garbage can model”. Bounded rationality characterises all “streams” of the decision-making processes. Moreo-ver, the decision-making process of the football clubs can be well illustrated in the framework, and the interplay of the different dimensions illustrates the different decision-making practices within the football clubs. References Amis, J., & Slack, T. (2003). Analysing sports organisations: Theory and practice. In B. Houlihan (Eds.), Sport & Society (pp. 201–217). London, England: Sage. Cohen, M.D., March, J.G., & Olsen, J.P. (1972). A garbage can model of organisational choice. Ad-ministrative Science Quarterly, 17, 1-25. Luhmann, N. (2000). Organisation und Entscheidung. Opladen: Westdeutscher Verlag. Mayring, P. (2010). Qualitative Inhaltsanalyse. Grundlagen und Techniken. Weinheim: Beltz. Skille, E. Å. (2013). Case study research in sport management: A reflection upon the theory of science and an empirical example. In S. Söderman & H. Dolles (Eds.), Handbook of research on sport and business (pp. 161–175). Cheltenham, England: Edward Elgar.
Resumo:
Mutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B-cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut-associated lymphoid tissues to maintain host-microbiota mutualism.
Resumo:
A search is presented for direct top squark pair production using events with at least two leptons including a same-flavour opposite-sign pair with invariant mass consistent with the Z boson mass, jets tagged as originating from b-quarks and missing transverse momentum. The analysis is performed with proton–proton collision data at √ s = 8 TeV collected with the ATLAS detector at the LHC in 2012 corresponding to an integrated luminosity of 20.3 fb−1. No excess beyond the Standard Model expectation is observed. Interpretations of the results are provided in models based on the direct pair production of the heavier top squark state (˜t2) followed by the decay to the lighter top squark state (˜t1) via ˜t2 → Z ˜t1, and for ˜t1 pair production in natural gaugemediated supersymmetry breaking scenarios where the neutralino (˜χ 01 ) is the next-to-lightest supersymmetric particle and decays producing a Z boson and a gravitino ( ˜G ) via the ˜χ 01→ Z ˜G process.
Resumo:
Welsch (Projektbearbeiter): Solidaritätsadresse des ungarischen an den österreichischen Reichstag in Wien: die Freiheit beider Länder ist bedroht. Option des Einmarschs ungarischer Truppen nach Österreich im Kampf gegen den gemeinsamen Feind, die "räuberischen Horden des Jellachich"
Resumo:
We elaborate on a recent study of a model of supersymmetry breaking we proposed recently, in the presence of a tunable positive cosmological constant, based on a gauged shift symmetry of a string modulus, external to the Standard Model (SM) sector. Here, we identify this symmetry with a global symmetry of the SM and work out the corresponding phenomenology. A particularly attracting possibility is to use a combination of Baryon and Lepton number that contains the known matter parity and guarantees absence of dimension-four and -five operators that violate B and L.
Resumo:
OBJECTIVE We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.
Resumo:
Small, cool planets represent the typical end-products of planetary formation. Studying the architectures of these systems, measuring planet masses and radii, and observing these planets' atmospheres during transit directly informs theories of planet assembly, migration, and evolution. Here we report the discovery of three small planets orbiting a bright (K-s = 8.6 mag) M0 dwarf using data collected as part of K2, the new ecliptic survey using the repurposed Kepler spacecraft. Stellar spectroscopy and K2 photometry indicate that the system hosts three transiting planets with radii 1.5-2.1 R-circle plus, straddling the transition region between rocky and increasingly volatile-dominated compositions. With orbital periods of 10-45 days the planets receive just 1.5-10x the flux incident on Earth, making these some of the coolest small planets known orbiting a nearby star; planet d is located near the inner edge of the system's habitable zone. The bright, low-mass star makes this system an excellent laboratory to determine the planets' masses via Doppler spectroscopy and to constrain their atmospheric compositions via transit spectroscopy. This discovery demonstrates the ability of K2 and future space-based transit searches to find many fascinating objects of interest.
Resumo:
Deficiency of the enzyme adenosine deaminase (ADA) results in severe lymphopenia in humans. Mice with an inactivating mutation in the ADA gene also exhibit profound lymphopenia, as well as pulmonary insufficiency and ribcage abnormalities. In fact, the mouse model has a phenotype that is remarkably similar to that of the human disease, making the mice valuable tools for unraveling the mechanism of lymphocyte destruction in absence of this housekeeping gene. T cell deficiency in ADA deficiency has been extensively studied by others, revealing a block in early thymocyte development. In contrast, our studies revealed that early B cell development in the bone marrow is normal. ADA-deficient mice, however, exhibit profound defects in germinal center formation, preventing antigen-dependent B cell maturation in the spleen. ADA-deficient spleen B cells display significant defects in proliferation and activation signaling, and produce more IgM than their normal counterparts, suggesting that extrafollicular plasmablasts are overrepresented. B cells from ADA-deficient mouse spleens undergo apoptosis more readily than those from normal mouse spleens. Levels of ADA's substrates, adenosine and 2′-deoxyadenosine, are elevated in both bone marrow and spleen in ADA-deficient mice. S ′-adenosyihomoeysteine hydrolase (SAH hydrolase) activity is significantly inhibited in both locales, as well. dATP levels, though, are only elevated in spleen, where B cell development is impaired, and not in bone marrow, where B cell ontogeny is normal. This finding points to dATP as the causative agent of lymphocyte death in ADA deficiency. ADA deficiency results in inhibition of the enzyme ribonucleotide reductase, thereby depleting nucleoside pools needed for DNA repair. Another mouse model that lacks a functional gene encoding a protein involved in DNA repair and/or cell cycle checkpoint regulation, p53-binding protein 1, exhibits blocks in T and B cell development that are similar to those seen in ADA-deficient mice. Unraveling the mechanisms of lymphocyte destruction in ADA deficiency may further understanding of lymphocyte biology, facilitate better chemotherapeutic treatment for lymphoproliferative diseases, and improve gene and enzyme therapy regimens attempted for ADA deficiency. ^