Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Entre neocorporativistas e deliberativos: uma interpretação sobre os paradigmas de análise dos fóruns participativos no Brasil Between the neo-corporatist and the deliberative: an interpretation of the paradigms in the analysis of the participatory forums in Brazil

Este artigo propõe o debate a respeito dos principais paradigmas a partir dos quais, usualmente, vêm sendo estudadas as propostas de ampliação dos canais de participação dos cidadãos na gestão das políticas públicas, análises que investigam os processos participativos ou desde o prisma dos "arranjos neocorporativos", ou por meio de uma perspectiva baseada na concepção de "democracia deliberativa". Visando este objetivo, o presente texto centra seus interesses na trajetória de duas das principais instâncias participativas que, nas últimas décadas, foram desenvolvidas no Brasil: os orçamentos participativos e os conselhos de políticas públicas. Estas instâncias foram avaliadas levando em consideração, especialmente, quatro elementos a) relações institucionais com os governos; b) perfil dos participantes; c) âmbito decisório e, d) dinâmicas de funcionamento. A partir do estudo destas características, os autores discutem sobre a capacidade dos paradigmas neocorporativo e deliberativo constituírem um modelo analítico consistente para a investigação de estruturas participativas dessemelhantes.<br>This article considers the debate on the major paradigms through which are usually examined the proposals to widen the channels of citizen participation in the management of public policies; studies that examine the participatory processes not only from the prism of the "neo-corporatist arrangements," but also through an approach based on the concept of "deliberative democracy." Aiming at this goal, this paper emphasizes the history of two of the main participatory instances that, in recent decades, have been developed in Brazil: the participatory budgeting and the public policy councils. These instances were evaluated taking into account four aspects in particular: a) institutional relationships with the government; b) the profile of the participants; c) the decision-making context; and d) the functioning dynamics. Considering the study of these characteristics, the authors discuss the ability of the neo-corporatist and the deliberative paradigms to create a consistent analytical model for the investigation of divergent participatory structures

Policy community defensora de direitos e a transformação do Conselho Nacional de Assistência Social

O artigo examina a ação estratégica de um ator coletivo, a policy community defensora da assistência social como direito dos cidadãos, a qual resultou não apenas na criação do Sistema Único de Assistência Social (SUAS), mas também na redefinição das funções do Conselho Nacional de Assistência Social (CNAS), ao final da década de 2000. Membros dessacommunity aproveitaram sucessivas janelas de oportunidades para apresentar aos decisores políticos propostas de solução para os problemas da extremada desigualdade social e pobreza, colocados no centro da agenda política e governamental desde o Governo Lula, iniciado em 2002. Uma dessas janelas de oportunidades abriu-se com a Operação Fariseu, em 2008, que expôs a existência de relações ilícitas entre conselheiros e entidades que recebiam certificação como beneficentes de assistência social e, portanto, vultosas isenções fiscais. A communityteve sucesso em retirar do fórum a prerrogativa de certificar e controlar as atividades de entidades 'beneficentes', transferindo-a às burocracias governamentais das áreas de assistência social, saúde e educação. Dessa forma, o CNAS, uma organização intermediária neocorporativa criada pela Lei Orgânica da Assistência Social, consolidou o seu papel na intermediação de interesses entre os diversos atores societais e estatais visando viabilizar a implementação das políticas definidas no nível federal de gestão que resultaram na estruturação do SUAS

Predictors of embolism and death in left-sided infective endocarditis: the European Society of Cardiology EURObservational Research Programme European Infective Endocarditis registry

International audienceBackground and Aims Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes. Methods The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016–18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality. Results There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was &gt;10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13–1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54–2.33, P &lt; .0001), history of heart failure (HR 1.53, 95% CI 1.21–1.93, P = .0004), creatinine &gt;2 mg/dL (HR 1.59, 95% CI 1.25–2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08–1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12–1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08–6.79, P &lt; .0001), alcohol abuse (HR 1.45, 95% CI 1.04–2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29–3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05–1.61, P = .016) (C-statistic = .68). Conclusions Prognosis after LSIE is determined by multiple factors, including vegetation size

Measurement of pion, kaon and proton production in proton-proton collisions at √s = 7 TeV

The measurement of primary π±, K±, p and p¯¯¯ production at mid-rapidity (|y|< 0.5) in proton-proton collisions at s√=7 TeV performed with ALICE (A Large Ion Collider Experiment) at the Large Hadron Collider (LHC) is reported. Particle identification is performed using the specific ionization energy loss and time-of-flight information, the ring-imaging Cherenkov technique and the kink-topology identification of weak decays of charged kaons. Transverse momentum spectra are measured from 0.1 up to 3 GeV/c for pions, from 0.2 up to 6 GeV/c for kaons and from 0.3 up to 6 GeV/c for protons. The measured spectra and particle ratios are compared with QCD-inspired models, tuned to reproduce also the earlier measurements performed at the LHC. Furthermore, the integrated particle yields and ratios as well as the average transverse momenta are compared with results at lower collision energies