6 research outputs found

    Turismo y gobernanza Âżen dĂłnde estamos? Aproximaciones teĂłricas y empĂ­ricas

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    La importancia que cobra la gobernanza en las sociedades contemporĂĄneas se relaciona con las transformaciones que estĂĄ asimilando el Estado y su entorno con respecto a la direcciĂłn que debe asumir la conducciĂłn de la sociedad, mediante la participaciĂłn de sus diversos actores, donde el Estado como agente central Ășnico de la conducciĂłn social se descarta como nĂșcleo de intervenciĂłn.El libro que coordina la Dra. Graciela Cruz JimĂ©nez, titulado Turismo y gobernanza. ÂżEn dĂłnde estamos? Aproximaciones teĂłricas y empĂ­ricas , tiene el propĂłsito de mostrar los esfuerzos que estĂĄn realizando especialistas de instituciones de educaciĂłn superior mexicanas y del extranjero, por enlazar la gobernanza al estudio del turismo. Se vislumbra que esta lĂ­nea de trabajo irĂĄ cobrando cada vez mayor auge y podrĂ­a posicionarse en el mediano plazo entre las lĂ­neas de investigaciĂłn turĂ­sticas, ante la relevancia que estĂĄ adquiriendo entre la comunidad cientĂ­fica

    Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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    BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

    Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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    International audienc

    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

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    International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

    No full text
    International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population
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