Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

The managerial state to the precarious state: federal public job in the decade of 1990

Made available in DSpace on 2012-09-06T01:12:30Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 758.pdf: 738007 bytes, checksum: 4389d0c03e64656f9183acecc1d1b784 (MD5) Previous issue date: 2004Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.Esta dissertação, apresentada ao programa de Mestrado em Saúde Pública da Escola Nacional de Saúde Pública ENSP, da Fundação Oswaldo Cruz FIOCRUZ, objetivou elaborar um estudo longitudinal, construindo evidências quantitativas que permitissem testar até que ponto os pressupostos pretendidos com a Reforma do Estado, implementada pelo Governo Federal a partir de 1995, especialmente a Reforma Administrativa, sistematizada pela Emenda Constitucional número 19, foram alcançados e quais foram os impactos causados no perfil do Emprego Público Federal no Brasil.Este estudo analisa as tendências institucionais e organizacionais da política para o Emprego Federal no setor público brasileiro na década de 1990, descrevendo os efeitos que a referida Reforma teve sobre o perfil do Emprego Público Federal.This dissertation, presented to the Public Health Master Course Program of the National School of Public Health – ENSP, Oswaldo Cruz Foundation – FIOCRUZ, aimed to elaborate a longitudinal study building quantitative evidences in order to test, to which extent, the intended assumptions of the State Reform, which was implemented by the Federal Government as from 1995, especially the Administrative Reform systematized by Constitutional Amendment number 19, have been achieved and their impacts on the federal public service in Brazil. This study analyzes institutional and organizational tendencies of politics to the federal job in the Brazilian public sector during the 1990s, describing the effects of the Reform, referred above, on the federal public job profil

Reestruturação produtiva e recomposições do trabalho e emprego. Um périplo pelas ‘novas’ formas de desigualdade social

O propósito do presente artigo consiste em questionar a inevitabilidade dos processos de segmentação e precarização das relações de trabalho e emprego, responsáveis pela inscrição de "novas" firmas de desigualdade social que alicerçam o actual modelo de desenvolvimento das economias e sociedades. Visa-se criticar os limites da lógica económica e financeira, de contornos globais, que configuram um "novo espírito do capitalismo", ou seja, uma espécie de divinização da ordem natural das coisas. Impõe-se fizer, por isso, um périplo analítico pelas transformações em curso no mercado de trabalho, acompanhado pela vigilância epistemológica que permita enquadrar e relativizar as (di)visões neoliberais e teses tecno-deterministas dominantes. A perspectivação de cenários sobre o futuro do trabalho encerrará este périplo, permitindo-nos alertar para os condicionalismos histórico-temporais. para a urgência de se desocultar o que de ideológico e político existe nas actuais lógicas de racionalização e para os processos de ressimbolização do trabalho e emprego enquanto "experiência social central" na contemporaneidade.The scope of this paper is to question the inevitability of the processes ti.seginentation and increased precariousness of the relations of labor and employment, which are res-ponsible for the introduction of "new" forms of social inequality that underpin the current model of development of economies and societies. It seeks to criticize the limits of global financial and economic logic, which constitute a "new spirit of capitalism," namely a kind of reverence for the natural order of things. It is therefore necessary to conduct an analytical survey of the ongoing changes in the labor market, accompanied by epistemological vigilance which makes it possible to see neoliberal (di)visions and dominant rechnodeterministic theses in context. The enunciation of scenarios on the future of work will conclude this survey and will make it possible to draw attention to both the historical and temporal constraints and to the urgent need to unveil what is ideological and political in the prevailing logic of rationalization and processes to reinstate work and employment as a "central social experience" in contemporary times