Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host

Viral mimicry of host cell structures has been postulated to curtail the B cell receptor (BCR) repertoire against persisting viruses through tolerance mechanisms. This concept awaits, however, experimental testing in a setting of natural virus–host relationship. We engineered mouse models expressing a monoclonal BCR specific for the envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV), a naturally persisting mouse pathogen. When the heavy chain of the LCMV-neutralizing antibody KL25 was paired with its unmutated ancestor light chain, most B cells underwent receptor editing, a behavior reminiscent of autoreactive clones. In contrast, monoclonal B cells expressing the same heavy chain in conjunction with the hypermutated KL25 light chain did not undergo receptor editing but exhibited low levels of surface IgM, suggesting that light chain hypermutation had lessened KL25 autoreactivity. Upon viral challenge, these IgM $^{low}$ cells were not anergic but up-regulated IgM, participated in germinal center reactions, produced antiviral antibodies, and underwent immunoglobulin class switch as well as further affinity maturation. These studies on a persisting virus in its natural host species suggest that central tolerance mechanisms prune the protective antiviral B cell repertoire

DIAGNÓSTICO SITUACIONAL DE UMA CLÍNICA DE TRATAMENTO ONCOLÓGICO DE BELO HORIZONTE

Introduction: Situational diagnosis is a tool for collecting, describing and analyzing data, which allows knowledge of points of improvement in a health institution. With the situational diagnosis it is possible to create interventions focused on the problems encountered during the study. Methodology: This is a descriptive field research carried out in an oncology clinic in Belo Horizonte. Results: During the study, the organizational structure, physical, human and material resources of the management instruments and the definition of nursing care indicators were evaluated. All data collected were described and compared to the current literature and standards. Conclusion: With the study, it was possible to identify positive and negative divergences between the clinic and the norms, but the positive ones stood out. In addition, the preparation of the Situational Diagnosis provides the academic with the ability to research, analyze data and develop a critical sense in relation to health institutions and the service offered by them.El diagnóstico situacional es una herramienta para la recopilación, descripción y análisis de datos, que permite el conocimiento de puntos de mejora en una institución de salud. Con el diagnóstico situacional es posible crear intervenciones centradas en los problemas encontrados durante el estudio. Metodología: Se trata de una investigación de campo descriptiva llevada a cabo en una clínica de oncología en Belo Horizonte. Resultados: Durante el estudio, se evaluó la estructura organizativa, los recursos físicos, humanos y materiales, los instrumentos de gestión y la definición de indicadores de cuidado de enfermería. Todos los datos recopilados fueron descritos y comparados con la literatura y los estándares actuales. Conclusión: Con el estudio, fue posible identificar divergencias positivas y negativas entre la clínica y las normas, pero las positivas estaban fuera. Además, la elaboración del diagnóstico situacional proporciona al académico la capacidad de investigar, analizar datos y desarrollar un sentido crítico en relación con las instituciones de salud y el servicio que ofrecen. O diagnóstico situacional é uma ferramenta de coleta, descrição e análise de dados, que permite o conhecimento de pontos de melhoria em uma instituição de saúde. Com o diagnóstico situacional é possível criar intervenções focadas nos problemas encontrados durante o estudo. Metodologia: Trata-se de uma pesquisa de campo descritiva realizada em uma clínica oncológica de Belo Horizonte. Resultados: Durante o estudo, foi avaliada a estrutura organizacional, recursos físicos, humanos e materiais, dos instrumentos gerenciais e a definição dos indicadores assistenciais de enfermagem. Todos os dados coletados foram descritos e comparados à literatura e normas vigentes. Conclusão: Com o estudo, foi possível identificar divergências positivas e negativas entre a clínica e as normas, porém as positivas se sobressaíram. Além disso, a elaboração do Diagnóstico Situacional proporciona ao acadêmico a capacidade de pesquisar, analisar dados e de desenvolver um senso crítico em relação às instituições de saúde e o serviço oferecido por elas

Seasonal precipitation in eastern Amazon during rainy season: regional observations and RegCM3 simulations

This paper presents a contribution on the climate modelling studies with emphasis on seasonal rainfall variability in eastern Amazonia, during the austral summer and autumn seasons (DJF and MAM). Based on RegCM3 regional climate simulations for a 26 years period (1982/83 to 2007/08) using high resolution domain scale (30 km) and two different convection schemes (Grell and MIT), it was investigated the model performance to simulate the regional pluviometric distribution in eastern Amazon, with reference to a new observational data base containing regional aspects extracted from a dense rain gauge station network. The quantitative analysis showed that RegCM3 presents systematic errors, especially those related to the dry bias in the Amapá and north/northeast of Pará using both schemes Grell and MIT, which indicate that the model does not reproduce ITCZ characteristics over equatorial Atlantic. The simulations using MIT also indicated wet bias in the southwest/south/southeast of Pará and north of Tocantins. Moreover, through composites technique, it was also investigated RegCM3 response to reproduce the anomalous spatial rainfall patterns in association with ENSO episodes and interhemispheric SSTa gradient phases across the intertropical Atlantic. The results showed that the model represented realistically well the spatial pattern related to the rainfall anomalies above (below) than normal in most of eastern Amazonia, during the known favourable scenarios, i.e., La Niña and south Atlantic SSTa gradient (unfavourable, i.e., El Niño and north Atlantic SSTa gradient).O presente trabalho apresenta uma contribuição aos estudos de modelagem climática com ênfase na variabilidade pluviométrica sazonal da Amazônia oriental, durante as estações de verão e outono (DJF e MAM). Baseado nos resultados das simulações regionais do RegCM3 para um período de 26 anos (1982/83 a 2007/08) e usando domínio em alta resolução espacial (30 Km) e dois diferentes esquemas de convecção (Grell e MIT), foi investigado o desempenho do modelo em simular a distribuição regional de precipitação sazonal na Amazônia oriental, com referência a um novo conjunto de dados observacional compilado com informações de uma ampla rede integrada de estações pluviométricas. As análises quantitativas evidenciaram que o RegCM3 apresenta erros sistemáticos, sobretudo aqueles relacionados com viés seco no Amapá e norte/nordeste do Pará usando ambos os esquemas Grell e MIT, os quais apontam que o modelo não reproduz as características da ZCIT sobre o Atlântico equatorial. As simulações usando MIT, também apresentaram viés úmido no sudoeste/sul/sudeste do Pará e norte do Tocantins. Além disso, através da técnica de composições, também foi investigado o desempenho do RegCM3 em reproduzir os padrões espaciais anômalos de precipitação sazonal em associação aos episódios ENOS, e as fases do gradiente térmico sobre o Atlântico intertropical. Os resultados demonstraram que o modelo conseguiu representar realisticamente bem o padrão espacial das anomalias pluviométricas acima (abaixo) do normal em grande parte da Amazônia oriental, durante os conhecidos cenários favoráveis, i.e., condições de La Niña e gradiente de aTSM para o Atlântico sul (desfavoráveis, i.e., El Niño e gradiente de aTSM para o Atlântico norte

INTERVENÇÃO DE ORIENTAÇÕES DE AUTOCUIDADO PARA PESSOAS EM SITUAÇÃO DE RUA: RELATO DE EXPERIÊNCIA

Introduction: nursing is responsible for providing assistance when there is a deficit in self-care, through actions of prevention, promotion, recovery and rehabilitation of health. Objective: to describe the experience of the operative group of self-care guidelines for the homeless population (PSR). Methodology: it is an experience report. Results: an operating group was created through the creation of posters and videos for guidance on self-care, using resources from the virtual environment. Final considerations: in view of the promotion of health education, the production of videos and posters were resources capable of making the operative group effective, developing the researchers' creativity, resoluteness and humanization.La enfermería es responsable de brindar atención cuando hay un déficit en el autocuidado, a través de acciones de prevención, promoción, recuperación y rehabilitación de la salud. Objetivo: describir la experiencia del grupo operativo de directrices de autocuciencia para la población sin hogar (PSR). Metodología: este es un informe de experiencia. Resultados: se llevó a cabo un grupo operativo a través de la elaboración de carteles y vídeos para orientación sobre el autocuidado, utilizando recursos del entorno virtual. Consideraciones finales: en vista de la promoción de la educación para la salud, la producción de vídeo y carteles fueron recursos capaces de realizar el grupo operativo, desarrollar la creatividad, la resolución de problemas y la humanización de los investigadores.A enfermagem é responsável pela prestação de assistência quando há um déficit no autocuidado, através de ações de prevenção, promoção, recuperação e reabilitação da saúde. Objetivo: descrever a experiência do grupo operativo de orientações de autocuidado para a população em situação de rua (PSR). Metodologia: trata-se de um relato de experiência. Resultados: foi realizado um grupo operativo por meio da elaboração de cartazes e vídeo para orientações sobre autocuidado, utilizando-se recursos de ambiente virtual. Considerações finais: diante da promoção de educação em saúde, a produção do vídeo e de cartazes foram recursos capazes de efetivar o grupo operativo, desenvolvendo a criatividade, resolutividade e humanização dos pesquisadores

Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years : Results from MAL-ED

Funding Information: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the National Institutes of Health/Fogarty International Center. This work was also supported by the Fogarty International Center, National Institutes of Health (D43-TW009359 to ETR). Author disclosures: BJJM, SAR, LEC, LLP, JCS, BK, RR, RS, ES, LB, ZR, AM, RS, BN, SH, MR, RO, ETR, and LEM-K, no conflicts of interest. Supplemental Tables 1–5 and Supplemental Figures 1–3 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. Address correspondence to LEM-K (e-mail: [email protected]). Abbreviations used: HOME, Home Observation for Measurement of the Environment inventory; MAL-ED, The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project; TfR, transferrin receptor; WPPSI, Wechsler Preschool Primary Scales of Intelligence.Peer reviewe

Early life child micronutrient status, maternal reasoning, and a nurturing household environment have persistent influences on child cognitive development at age 5 years: Results from MAL-ED

Background: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. Objective: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. Methods: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. Results: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (β: −1.81, 95% CI: −2.75, −0.86), number of years of maternal education (β: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (β: 0.09, 95% CI: 0.03, 0.15), household assets score (β: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (β: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. Conclusions: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.publishedVersio

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

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