954 resultados para Fang (West African people)


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Thesis (Master's)--University of Washington, 2016-06

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Thesis (Ph.D.)--University of Washington, 2016-06

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Background - Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD. Methods and Results - We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin ( 40 mg daily) versus placebo. Of 19 700 subjects, 4491 ( 22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m(2) body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome ( adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome ( HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function ( HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD ( adjusted HR 0.86, 95% CI 0.74 to 1.00, P = 0.045). Conclusions - Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.

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West Nile Virus (WNV) is a mosquito-borne flavivirus with a rapidly expanding global distribution. Infection causes severe neurological disease and fatalities in both human and animal hosts. The West Nile viral protease (NS2B-NS3) is essential for post-translational processing in host-infected cells of a viral polypeptide precursor into structural and functional viral proteins, and its inhibition could represent a potential treatment for viral infections. This article describes the design, expression, and enzymatic characterization of a catalytically active recombinant WNV protease, consisting of a 40-residue component of cofactor NS2B tethered via a noncleavable nonapeptide (G(4)SG(4)) to the N-terminal 184 residues of NS3. A chromogenic assay using synthetic para-nitroanilide (pNA) hexapeptide substrates was used to identify optimal enzyme-processing conditions (pH 9.5, I < 0.1 M, 30% glycerol, 1 mM CHAPS), preferred substrate cleavage sites, and the first competitive inhibitor (Ac-FASGKR- H, IC50 &SIM; 1 μM). A putative three-dimensional structure of WNV protease, created through homology modeling based on the crystal structures of Dengue-2 and Hepatitis C NS3 viral proteases, provides some valuable insights for structure-based design of potent and selective inhibitors of WNV protease.

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Background: evaluation of the 'Keep Well At Home' (KWAH) Project in West London indicated that a programme of screening persons aged 75 and over had not reduced rates of emergency attendances and admissions to hospital. However, coverage of the target population was incomplete. The present analysis addresses 'efficacy'-whether individuals who completed the screening protocol as intended did subsequently use Accident & Emergency (A&E) services less often. Methods: the target population was divided into five groups, depending on whether an individual had completed none, one or both phases of screening, and whether deviations from the protocol related to incomplete coverage or refusal to participate further. We ascertained use of emergency services before screening and for up to 3 years afterwards by linkage of records from KWAH to those of local A&E Departments. Patterns of emergency care were examined as crude races and, via proportional hazards models, after adjustment for available confounders. Results: there was an increase of 51% (95% CI 22-86%) in the crude rate of emergency admissions in the year after first-phase screening compared with the 12 months before assessment. This was most obvious in individuals deemed at high risk who also underwent the second-phase assessment (adjusted hazard ratio relative to individuals not 'at risk'= 2.33; 95% CI 1.59-3.42). Conclusions: the available data do not allow us to distinguish between several possible explanations for the paradoxical increase in use of emergency services. However, what seem to be sensible policies do not necessarily have their intended effects when implemented in practice.

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The flavivirus West Nile virus (WNV) has spread rapidly throughout the world in recent years causing fever, meningitis, encephalitis, and fatalities. Because the viral protease NS2B/NS3 is essential for replication, it is attracting attention as a potential therapeutic target, although there are currently no antiviral inhibitors for any flavivirus. This paper focuses on elucidating interactions between a hexapeptide substrate (Ae-KPGLKR-p-nitroanilide) and residues at S1 and S2 in the active site of WNV protease by comparing the catalytic activities of selected mutant recombinant proteases in vitro. Homology modeling enabled the predictions of key mutations in VWNV NS3 protease at S1 (V115A/F, D129A/ E/N, S135A, Y150A/F, S160A, and S163A) and S2 (N152A) that might influence substrate recognition and catalytic efficiency. Key conclusions are that the substrate P1 Arg strongly interacts with S1 residues Asp-129, Tyr-150, and Ser-163 and, to a lesser extent, Ser-160, and P2 Lys makes an essential interaction with Asn-152 at S2. The inferred substrate-enzyme interactions provide a basis for rational protease inhibitor design and optimization. High sequence conservation within flavivirus proteases means that this study may also be relevant to design of protease inhibitors for other flavivirus proteases.

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West Nile Virus is becoming a widespread pathogen, infecting people on at least four continents with no effective treatment for these infections or many of their associated pathologies. A key enzyme that is essential for viral replication is the viral protease NS2B-NS3, which is highly conserved among all flaviviruses. Using a combination of molecular fitting of substrates to the active site of the crystal structure of NS3,site-directed enzyme and cofactor mutagenesis, and kinetic studies on proteolytic processing of panels of short peptide substrates, we have identified important enzyme-substrate interactions that define substrate specificity for NS3 protease. In addition to better understanding the involvement of S2, S3, and S4 enzyme residues in substrate binding, a residue within cofactor NS2B has been found to strongly influence the preference of flavivirus proteases for lysine or arginine at P2 in substrates. Optimization of tetrapeptide substrates for enhanced protease affinity and processing efficiency has also provided important clues for developing inhibitors of West Nile Virus infection.

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Discriminatory language became an important social issue in the west in the late twentieth century, when debates on political correctness and minority rights focused largely on the issue of respect in language. Japan is often criticized for having made only token attempts to address this issue. This paper investigates how one marginalized group—people with disabilities—has dealt with discriminatory and disrespectful language. The debate has been played out in four public spaces: the media, the law, literature, and the Internet. The paper discusses the kind of language, which has generated protest, the empowering strategies of direct action employed to combat its use, and the response of the media, the bureaucracy, and the literati. Government policy has not kept pace with social change in this area; where it exists at all, it is often contradictory and far from clear. I argue that while the laws were rewritten primarily as a result of external international trends, disability support groups achieved domestic media compliance by exploiting the keen desire of media organizations to avoid public embarrassment. In the absence of language policy formulated at the government level, the media effectively instituted a policy of self-censorship through strict guidelines on language use, thereby becoming its own best watchdog. Disability support groups have recently enlisted the Internet as an agent of further empowerment in the ongoing discussion of the issue.

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This article analyses the ambiguous and contradictory relationship between the Orthodox Church and the communist regime during the first two years of the Romanian People's Republic. The installation of communism and the process of Stalinisation led to an unprecedented control of the church. The church was actively employed in propaganda and the regime imposed its own people in the hierarchy. On the one hand, Romanian communists followed the Soviet model regarding the place of the church in the communist state while, on the other hand, the church hierarchy adapted to the new political system by creating a theory of 'social apostolate'. Lacking popular support, the communists used the church as an instrument through which they could acquire the political support of the masses. The church thus enjoyed a favoured position in society mainly because the communists employed it in their ideological expansionism and confrontation with the West.

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People and their performance are key to an organization's effectiveness. This review describes an evidence-based framework of the links between some key organizational influences and staff performance, health and well-being. This preliminary framework integrates management and psychological approaches, with the aim of assisting future explanation, prediction and organizational change. Health care is taken as the focus of this review, as there are concerns internationally about health care effectiveness. The framework considers empirical evidence for links between the following organizational levels: 1. Context (organizational culture and inter-group relations; resources, including staffing; physical environment) 2. People management (HRM practices and strategies; job design, workload and teamwork; employee involvement and control over work; leadership and support) 3. Psychological consequences for employees (health and stress; satisfaction and commitment; knowledge, skills and motivation) 4. Employee behaviour (absenteeism and turnover; task and contextual performance; errors and near misses) 5. Organizational performance; patient care. This review contributes to an evidence base for policies and practices of people management and performance management. Its usefulness will depend on future empirical research, using appropriate research designs, sufficient study power and measures that are reliable and valid.

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There is growing evidence available to suggest that Human Resource Management (HRM) practice is an important predictor of organizational performance. Drawing upon organizational learning perspectives, we argue that HRM systems also have the potential to promote organizational innovation. We present longitudinal data from thirty-five UK manufacturing organizations to suggest that effective HRM systems – incorporating sophisticated approaches to recruitment and selection, induction, appraisal and training – predict organizational innovation in products and production technology. We further show that organizational innovation is enhanced where there is a supportive learning climate, and inhibited (for innovation in production processes) where there is a link between appraisal and remuneration.

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The oharaoter of right-wing extremism in the Federal Republic has undergone extensive transformations in the seventies. As electoral support for the extreme Right declined, a whole range of new groupings emerged pursuing a militant extra-parliamentary strategy. Essential charaoteristics are an increasing tendency to use violence and a close ideological affinity to the NSDAP. They attract a growing number of young people. The increasing susceptibility of young people to rightist ideologies coincides with an economic recession of which young people especially are the victims. Widespread ignorance about Nazism and the prevalence of anti-democratic political attitudes constitute important contributary factors and point to a considerable potential for right-extremism in the Federal Republic., This potential can be attributed. to the negative effects of much of the material dealing with the NS past, to serious deficiencies in the area of historical-political education in schools and, above all, to the absence of any :real process of "coming to terms with the past" in the postwar period. Neo-Nazism is not completely isolated from other trends in West German society. Rightist elements within the established party system and broad sections of the population hold similar views and attitudes. This similarity, linked with an over-exaggerated concern with a perceived threat from the extreme Left may explain the absence of any concerted effort to deal with nee-Nazi tendencies. The response of the courts exemplifies a widespread tendency to under-estimate the significance of the extreme Right. Opposition to the Right is restricted primarily to those circles which suffered most under the Nazi regime. The analysis suggests that one must reject the simplistic view that at the present time the Right does not constitute a serious threat to West German democracy. The study evaluates the wide range of views to be found in secondary sources on the subject of neo-Nazism and is :intended, to contribute to the ongoing discussion conceming the potential for right-extremism in West Germany.