Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Use Of Near Infrared Emission Spectroscopy In The Study Of Supporting Materials And Stationary Phases For Liquid Chromatography.

Near infrared emission spectroscopy (NIRES) has been investigated in the study of different materials employed in liquid chromatography. The samples were heated in a nitrogen atmosphere and the emission spectra were obtained using a lab-made NIRES instrument. Through principal component analysis (PCA) using the raw emission spectra, it was possible to distinguish different materials according to their physical and/or chemical characteristics. Linear relationships between emissivity spectra and the contents of the coating material or the specific surface areas was observed for stationary phases or bare silicas, respectively. Furthermore, the thermal stability of stationary phases could be followed in real time.1122174-

Efeitos de diferentes tipos de exercício nos parâmetros do andar de idosas

O tipo de exercício, a intensidade e a frequência são fatores importantes para produzir mudanças na velocidade de andar. O objetivo do estudo foi comparar os efeitos de diferentes tipos de exercício nos parâmetros cinemáticos do andar de idosas, considerando as características antropométricas, a capacidade funcional e o nível de atividade física. Participaram do estudo 56 idosas que foram agrupadas de acordo com o envolvimento, a mais de seis meses, na prática específica de uma atividade: dança (n = 10), musculação (n = 10), hidroginástica (n = 12) e caminhada (n = 11). Além disso, um grupo de idosas inativas (n = 13), sem envolvimento em atividade física regular por pelo menos dois meses, também participou do estudo. Foram mensurados o nível de atividade física (Questionário de Baecke), a capacidade funcional (Bateria da AAHPERD) e os parâmetros cinemáticos do andar (comprimento da passada e do passo, duração e velocidade da passada, cadência e duração das fases de suporte simples, balanço e duplo suporte). Os resultados revelaram que o nível de atividade física do grupo Controle foi diferente dos demais grupos que praticam atividades físicas. Em relação à capacidade funcional, apenas o componente força apresentou diferenças entre os grupos, indicando que o grupo Controle difere do grupo musculação. Quanto às variáveis do andar, o grupo Controle foi estatisticamente diferente apenas do grupo dança, tanto no comprimento do passo como no comprimento da passada. Pode-se concluir que a capacidade funcional e os parâmetros do andar dos idosos ativos e sedentários apresentam poucas diferença