52 research outputs found

    Bound computation of dependability and performance measures

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    A model-based evaluation of Marine Protected Areas: the example of eastern Baltic cod (Gadus morhua callarias L.).

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    The eastern Baltic cod stock collapsed as a consequence of climate-driven adverse hydrographic conditions and overfishing and has remained at historically low levels. Spatio-temporal fishing closures [Marine Protected Areas (MPAs)] have been implemented since 1995, to protect and restore the spawning stock. However, no signs of recovery have been observed yet, either suggesting that MPAs are an inappropriate management measure or pointing towards suboptimal closure design. We used the spatially explicit fishery simulation model ISIS-Fish to evaluate proposed and implemented fishery closures, combining an age-structured population module with a multifleet exploitation module and a management module in a single model environment. The model is parameterized based on (i) the large amount of biological knowledge available for cod and (ii) an analysis of existing spatially disaggregated fishery data. As the population dynamics of eastern Baltic cod depend strongly on the climate-driven hydrographic regime, we considered two production regimes of the stock. MPAs were only effective for stock recovery when they reduced overall fishing effort. The performance of MPAs needs to be evaluated relative to environmental regimes, especially for stocks facing strong environmental variability

    Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

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    Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

    Thrombopénie immunologique : de la physiopathologie aux traitements

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    International audienceImmune thrombocytopenia (ITP) is a rare autoimmune disease due to an immune peripheral destruction of platelets and an inappropriate platelet production. The pathogenesis of ITP is now better understood: it involves a humoral immune response which dependents on the stimulation of B cells by specific T cells called T follicular helper cells, leading to their differentiation into plasma cells that produce antiplatelet antibodies thus promoting the phagocytosis of platelets mainly by splenic macrophages. The deciphering of ITP pathogenesis has led to a better understanding of the inefficiency of treatments such as rituximab, although it has not provided yet the determination of biological predictive factor of response to treatments. Moreover, new therapeutic perspectives have been opened in the last few years with the development of molecules targeting FcÎł receptor signalling such as Syk inhibitor, or molecules increasing the clearance of pathogenic autoantibodies such as inhibitors of the neonatal Fc receptor (FcRn)
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