Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

[pt] ANÁLISE DO COMPORTAMENTO MECÂNICO DE PAVIMENTO REFORÇADO COM GEOSSINTÉTICO SOB CARREGAMENTO CÍCLICO EM MODELO FÍSICO DE VERDADEIRA GRANDEZA

A busca por soluções geotécnicas que aumentem a vida útil das estruturas e também possam economizar material natural levou ao desenvolvimento de produtos conhecidos como geossintéticos. Dentre as várias famílias de geossintéticos, foram criados elementos que funcionassem como reforço de base-subleito em pavimentos na condição de subleito muito deformável, denominadas geogrelhas. O presente trabalho teve o objetivo de analisar o comportamento mecânico de uma estrutura de pavimento reforçado com geogrelha, submetida à aplicação de carregamento cíclico e à variação de umidade do material do subleito. Foi utilizado para o desenvolvimento dos ensaios um modelo físico de verdadeira grandeza no qual foi construída a estrutura do pavimento composta de um subleito de 100 cm de espessura e uma camada de base de brita de 20 cm de espessura. Nesta estrutura analisou-se o efeito da inserção do geossintético como reforço de camada de base e a variação da umidade do subleito. As medidas fornecidas pelos transdutores de deslocamentos (LVDTs) foram os parâmetros de comparação entre a estrutura de pavimento com e sem reforço no decorrer dos ensaios. Os refletômetros no domínio do tempo (TDRs) monitoraram a variação da umidade do subleito. A comparação entre os deslocamentos da estrutura reforçada e não reforçada permitiu determinar a influência do reforço mostrando-se eficiente na redução dos deslocamentos superficiais verticais. A utilização de equipamentos portáteis para avaliar o comportamento mecânico do pavimento in situ mostraram ser uma ferramenta recomendável para estudos defletométricos de forma pontual no pavimento.The search for geotechnical solutions that increase the life time of structures and can also reduce the use of natural materials carried out to the development of products known as geosynthetic. Among the various families of geosynthetics, have been created elements which function as reinforcement of base-subgrade of pavements when the condition of the subgrade is very deformable, called geogrids. This study had the objective to analyze the mechanical behavior of a structure of geogrid reinforced pavement, submitted to the application of cyclic loading and variation in subgrade layer moisture. It was used for the development of tests a true scale physical model, in which was built a structure of pavement composed of a subgrade with 100 cm of thickness and a gravel layer of 20 cm of thickness. In this structure has been analyzed the effect of insertion of geogrid like base layer reinforcement and a variation in subgrade layer moisture. The measures provided by the displacement transducers (LVDTs) were the parameters of comparison between a structure of pavement with and without reinforcement during the tests. The Time Domain Reflectometry (TDR) monitored the variation of moisture from the subgrade. The comparison between the displacements of reinforced and unreinforced structure allowed determine the influence of reinforcement showing to be efficient to reduce superficial vertical displacements. The use of mobile devices to evaluate the mechanical behavior of the pavement in situ proved to be a tool recommended for punctual studies on pavements