146 research outputs found

    OC6 project Phase IV: Validation of numerical models for novel floating offshore wind support structures

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    \ua9 Copyright: This paper provides a summary of the work done within Phase IV of the Offshore Code Comparison Collaboration, Continued with Correlation and unCertainty (OC6) project, under International Energy Agency Wind Technology Collaboration Programme Task 30. This phase focused on validating the loading on and motion of a novel floating offshore wind system. Numerical models of a 3.6MW horizontal-axis wind turbine atop the TetraSpar floating support structure were compared using measurement data from a 1:43-Froude-scale test performed in the University of Maine\u27s Alfond Wind-Wave (W2) Ocean Engineering Laboratory. Participants in the project ran a series of simulations, including system equilibrium, surge offsets, free-decay tests, wind-only conditions, wave-only conditions, and a combination of wind and wave conditions. Validation of the models was performed by comparing the aerodynamic loading, floating support structure motion, tower base loading, mooring line tensions, and keel line tensions. The results show a relatively good estimation of the aerodynamic loading and a reasonable estimation of the platform motion and tower base fore-aft bending moment. However, there is a significant dispersion in the dynamic loading for the upwind mooring line. Very good agreement was observed between most of the numerical models and the experiment for the keel line tensions

    MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression

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    Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT) cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i) mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB); ii) the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT) or γδ T cells, and is characterized by production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2, but not IL-17A; iii) high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1) participation, is required for MAIT cell activation; iv) MAIT cell responses to SEB can occur in a T cell receptor (TCR) Vβ-specific manner but are largely contributed by IL-12 and IL-18; v) as MAIT cells are primed by SAgs, they also begin to develop a molecular signature consistent with exhaustion and failure to participate in antimicrobial defense. Accordingly, they upregulate lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin-3 (TIM-3), and/or programmed cell death-1 (PD-1), and acquire an anergic phenotype that interferes with their cognate function against Klebsiella pneumoniae and Escherichia coli; vi) MAIT cell hyperactivation and anergy co-utilize a signaling pathway that is governed by p38 and MEK1/2. Collectively, our findings demonstrate a pathogenic, rather than protective, role for MAIT cells during infection. Furthermore, we propose a novel mechanism of SAg-associated immunosuppression in humans. MAIT cells may therefore provide an attractive therapeutic target for the management of both early and late phases of severe SAg-mediated illnesses

    Factors associated with smoking among tuberculosis patients in Spain

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    BACKGROUND: To determine the prevalence of smoking and analyze associated factors in a cohort of patients diagnosed with tuberculosis (TB) in Spain between 2006 and 2013. METHODS: Multicenter, cross-sectional, descriptive, observational study using a national database of TB patients, using logistic regression to calculate odds ratios (OR) and confidence intervals (CI). RESULTS: We analyzed 5,846 cases (62 % men, mean age 39 years, 33 % foreigners). 23.4 % were alcohol abuser, 1.3 % were injected drug users (IDU), 4.6 % were co-infected with HIV, and 7.5 % had a history of TB treatment. 6.6 % and 0.8 % showed resistance to one and multiple drugs, respectively. The predominant clinical presentation was pulmonary (71 %) with a cavitary radiological pattern in 32.8 % of cases. 82 % of cases were confirmed microbiologically, and 54 % were smear-positive microscopy. 2,300 (39.3 %) patients were smokers. The following factors were associated with smoking: male sex (OR = 2.26;CI:1.97;2.60), Spanish origin (OR = 2.79;CI:2.40–3.24), alcoholism (OR = 2.85;CI:2.46;3.31), IDU (OR = 2.78;CI:1.48;5.52), homelessness (OR = 1.99;CI:1.14–3.57), pulmonary TB (OR = 1.61;CI:1.16;2.24), cavitary radiological pattern (OR = 1.99;CI:1.43;2.79) and a smear-positive microscopy at the time of diagnosis (OR = 1.39;CI:1.14;1.17). CONCLUSIONS: The prevalence of smoking among TB patients is high. Smokers with TB have a distinct sociodemographic, clinical, radiological and microbiological profile to non-smokers

    Cuidados biomédicos de saúde em Angola e na Companhia de Diamantes de Angola, c. 1910-1970

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    Pretende-se caracterizar a prestação de cuidados biomédicos em Angola durante a atividade da Companhia de Diamantes de Angola. Uma análise comparativa de políticas e práticas de saúde pública de vários atores coloniais, como os serviços de saúde da Companhia, sua congénere do Estado e outras empresas coloniais, revelará diferenças de investimento na saúde, isto é, instalações e pessoal de saúde, e tratamentos. Este escrutínio bem como as condições de vida iluminarão o carácter idiossincrático e central dos serviços de saúde da Companhia em termos de morbimortalidade em Angola, e a centralidade destes para as representações de um império cuidador
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