Classificações em psiquiatria: uma história conceitual

BACKGROUND: Historical accounts of psychiatric classifications have hitherto been written in terms of a 'received view'. This contains two assumptions, that: (i) the activity of classifying is inherent to the human mind; and (ii) psychiatric 'phenomena' a restable natural objects. OBJECTIVES: The aim of this article is to provide an outline of the evolution of psychiatric classifications from the perspective of conceptual history. This is defined as a theoretical and empirical inquiry into the principles, sortal techniques and contexts in which alienists carried out their task. It assumes that all psychiatric classifications are cultural products, and endeavours to answer the question of whether classificatory models imported from the natural sciences can be applied to man-made constructs (such as mental illness) definitionally based on 'personalised semantics'. METHODS: Exemplars of classificatory activity are first mapped and contextualised. Then, it is suggested that in each historical period crafting classifications has been like playing a game of chess with each move being governed by rules. This is illustrated by offering an analysis of the 1860-1861 French debate on classification. RESULTS AND CONCLUSIONS: (1) Medicine is not a contemplative but a modificatory activity and hence classifications are only valuable if they can release new information about the object classified. (2) It should not be inferred from the fact that psychiatric classifications are not working well (i.e. that they only behave as actuarial devices) that they must be given up. Conceptual work needs to continue to identify 'invariants' (i.e. stable elements that anchor classifications to 'nature'. (3) Because mental disorders are more than unstable behavioural epiphenomena wrapped around stable molecular changes, 'neurobiological' invariants may not do. Stability depends upon time frames. Furthermore, it is unlikely that gene-based classifications will ever be considered as classifications of mental disorders. For once, they would have low predictive power because of their lack of information about the defining codes of mental illness. 'Social' and 'psychological' invariants have problems of their own.CONTEXTO: As análises históricas sobre classificações psiquiátricas foram até agora escritas sob uma perspectiva preconcebida. Essas análises assumem duas pressuposições: 1) a ação de classificar é inerente à mente humana; e 2) os 'fenômenos' psiquiátricos são objetos naturais estáveis. OBJETIVOS: O objetivo deste artigo é fornecer um esboço da evolução das classificações psiquiátricas sob o ponto de vista da história conceitual*, que pode ser definida como uma investigação teórica e empírica dos princípios, das técnicas e dos contextos nos quais os alienistas conduziram sua tarefa classificatória. Assume-se que todas as classificações psiquiátricas sejam produtos culturais e procura-se responder à questão da possibilidade de os modelos classificatórios importados das ciências naturais serem aplicados a construtos humanos (tais como doença mental), por definição baseados em 'semânticas personalizadas'. MÉTODOS: Exemplares da atividade classificatória são primeiramente mapeados e contextualizados. Sugere-se, então, que em cada período histórico a elaboração de classificações tenha-se dado como num jogo de xadrez, em que todo movimento é governado por regras. Isso é ilustrado por uma análise do debate francês sobre classificações, ocorrido em 1860-1861. RESULTADOS E CONCLUSÕES: 1) A medicina não é uma atividade contemplativa, mas, sim, uma atividade modificadora; portanto, as classificações têm valor apenas na medida em que possam produzir novas informações sobre os objetos classificados. 2) O fato de as classificações não funcionarem bem (ou seja, de se comportarem como meros instrumentos descritivos) não significa que devam ser abandonadas. O trabalho conceitual precisa continuar identificando 'invariantes' (ou seja, elementos estáveis que ancorem as classificações à 'natureza'). 3) Na medida em que os transtornos mentais representam mais do que epifenômenos comportamentais envolvendo alterações moleculares estáveis, as invariantes 'neurobiológicas' podem não funcionar adequadamente. A estabilidade depende de contingências temporais (conjunturas). Além disso, é improvável que classificações baseadas em genes venham a ser consideradas como classificação de transtornos mentais. Elas teriam baixo poder preditivo pela falta de informação sobre os códigos definidores de doença mental. Por outro lado, as invariantes 'sociais' e 'psicológicas' têm seus próprios problemas

Sucrose Monoester Micelles Size Determined by Fluorescence Correlation Spectroscopy (FCS)

One of the several uses of sucrose detergents, as well as other micelle forming detergents, is the solubilization of different membrane proteins. Accurate knowledge of the micelle properties, including size and shape, are needed to optimize the surfactant conditions for protein purification and membrane characterization. We synthesized sucrose esters having different numbers of methylene subunits on the substituent to correlate the number of methylene groups with the size of the corresponding micelles. We used Fluorescence Correlation Spectroscopy (FCS) and two photon excitation to determine the translational D of the micelles and calculate their corresponding hydrodynamic radius, Rh. As a fluorescent probe we used LAURDAN (6-dodecanoyl-2-dimethylaminonaphthalene), a dye highly fluorescent when integrated in the micelle and non-fluorescent in aqueous media. We found a linear correlation between the size of the tail and the hydrodynamic radius of the micelle for the series of detergents measured

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Advancing South American Water and Climate Science through Multidecadal Convection-Permitting Modeling

South America’s hydroclimate sustains vibrant communities and natural ecosystems of extraordinary biodiversity including the Andes Cordillera, and the Orinoco, La Plata, and Amazon basins. Global warming and land-use change are endangering ecosystem health, exacerbating hydrometeorological extremes, and threatening water and food security for millions of people on the continent (Castellanos et al. 2022). Reductions in rainfall and streamflow have been observed in southern Amazonia, the Cerrado region, northeast Brazil, and Chile (Muñoz et al. 2020; Garreaud et al. 2020; Espinoza et al. 2019; Fu et al. 2013). The increased aridity has affected agricultural yield, water supply for reservoirs, hydropower generation and impacted tens of millions of people in the large metropolitan areas of Sao Paulo, Rio de Janeiro, and Santiago de Chile (Nobre et al. 2016). Andean glaciers, an important source of water, have lost 30% of their area in the tropics and up to 60% in the southern Andes—the highest glacier mass loss rates in the world (Braun et al. 2019; Dussaillant et al. 2019; Reinthaler et al. 2019; Masiokas et al. 2020; Fox-Kemper et al. 2021). Conversely, southeastern South America is facing increasing annual rainfall and intensification of heavy precipitation since the early twentieth century (Doyle et al. 2012; Barros et al. 2015; Pabón-Caicedo et al. 2020; Arias et al. 2021; Gutiérrez et al. 2021; Morales-Yokobori 2021; Seneviratne et al. 2021). Extreme precipitation is projected to intensify throughout the continent (Arias et al. 2021; Seneviratne et al. 2021). This poses significant risk to people and infrastructure along the Andes and other mountainous areas, particularly for lower-income communities living in informal housing (Poveda et al. 2020; Ozturk et al. 2022). The overarching goals of the SAAG community are twofold: improved physical understanding and application-relevant research. Two multidecadal convection-permitting simulations are at the heart of SAAG. The historical simulation will allow us to validate the model and better understand detailed hydroclimate features over the continent, while the future climate simulation will show the projected changes of these features in a warmer climate. Furthermore, SAAG scientists are working directly with local communities, so the information can be used for improved decision making. The specific goals and science questions are as follows; goal 1 Physical understanding: Advance insights and improve prediction of key hydroclimate processes in the region including projected changes in a changing climate and Goal 2, Provide information that can be used by local communities and stakeholders for better informed decision-making in a changing climate

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts