Standby power consumption estimation by interacting leakage current mechanisms in nanoscaled CMOS digital circuits

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Reclassification of the intermediate group classified according to heartscore taking in considertaion individual genetic predisposition to coronary artery disease

PosterIntroduction: Cardiovascular risk stratification has included traditional cardiovascular risk factors (TRF) including tobacco, cholesterol and blood pressure adjusted to age and sex. The utility of genetic risk scores (GRS) as predictors of cardiovascular risk remains inconclusive. Objective: We intended to evaluate the ability of a multilocus GRS within the intermediate risk subgroup, defined by the European Heart score, to add predictive power for the association with coronary artery arterial disease (CAD). Methods: After applying European SCORE (ES) stratification to a total population of 2703 Portuguese individuals, 639 individuals with 59.0 ± 4.3 years were considered to be at intermediate risk subgroup (2 Results: GRS was an independent predictor for CAD (OR=2.411; pinfo:eu-repo/semantics/publishedVersio

Associação independente da variante rs1333049, no locus 9p21, com a doença coronária, numa população portuguesa

Funding: This study was supported by the European Regional Development Fund’s Operational Programme for the Enhancement of Economic Potential and Territorial Cohesion for the Autonomous Region of Madeira (INTERVIR+).Introduction: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. Aim: To investigate whether the SNP rsl333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. Methods: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.7±8.9 years, 79.9% male) and 683 controls without coronary disease (mean age 53.3±10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. Results: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR=1.33; p=0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR=1.34, p=0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR=1.05, p=0.670). After logistic regression analysis, the CC genotype remained in the equation with 0R=1.7; p=0.018 and CG with OR=I.5, p=0.048. Conclusion: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.publishersversionpublishe

Livro Vermelho dos Vertebrados de Portugal

Os Livros Vermelhos têm sido reconhecidos, pelas entidades responsáveis pela conservação da natureza, as organizações não-governamentais, a co- munidade científica e os decisores de projectos com incidência no ordena- mento e gestão do território, como elementos de consulta e instrumento de apoio à tomada de decisão de inegável utilidade. Neles se indica o esta- tuto de ameaça das espécies selvagens, de acordo com critérios quantitati- vos para avaliar níveis de risco de extinção e, ainda, informação sobre as populações, causas de ameaça e medidas de conservação. Estes são documentos em permanente actualização, reflectindo cada edição o melhor conhecimento científico disponível, e a sua elaboração deve ser considerada como uma tarefa de interesse público e mobilizadora de todos os que disponham de informação relevante e actualizada para a avaliação do estatuto das diferentes espécies. Um Livro Vermelho é ainda uma chamada de atenção e uma tomada de consciência perante a diminuição da diversidade biológica à escala global. Desde 1500, registou-se a extinção de 92 espécies de peixes, 5 de anfíbios, 22 de répteis, 131 de aves e 87 de mamíferos (Hylton-Taylor 2000). Regularmente, a União Mundial para a Conservação (IUCN) actualiza e alarga a avaliação do risco de extinção à escala mundial a um ainda maior número de espécies. Assim, de acordo com o exercício realizado em 2004 (IUCN 2004a) verifica-se o seguinte: para os mamíferos, a avaliação revela 23% de espécies ameaçadas, correspondente a 20% do total das espécies co- nhecidas; nas aves, a avaliação perfaz a quase totalidade das espécies conhecidas e atinge os 12% de espécies ameaçadas; os répteis avaliados apresentam uma percentagem muito elevada de espécies ameaçadas (61%), muito embora esta percentagem corresponda apenas a 4% do to- tal das espécies conhecidas; os anfíbios ameaçados são cerca de 31% das espécies conhecidas; nos peixes, grupo cuja proporção de avaliações está muito aquém das espécies conhecidas, os resultados revelam 46% de ameaçadas, correspondentes a 3% do total de espécies conhecidas. Nesta edição são listadas as espécies de peixes dulciaquícolas e migradores, anfíbios, répteis, aves e mamíferos que ocorrem em Portugal. Mas este é sobretudo o livro das espécies ameaçadas que enfrentam risco de extinção e a que, por isso, foram atribuídas as categorias de .Vulnerável., .Em Perigo. ou .Criticamente em Perigo.; é também o livro de algumas espécies às quais foi atribuída a categoria de .Quase Ameaçado. e ainda daquelas com .Informação Insuficiente. sobre a sua distribuição, requisitos de habitat, dimensão ou tendência populacional (entre outros aspectos) o que impediu a avaliação do risco de extinção. Atribuído um estatuto, identificam-se ainda os factores de ameaça, devendo estes ser entendidos como os fenómenos ou processos que sendo contí- nuos, esporádicos ou recorrentes, localizados ou generalizados, afectam as populações ou alteram a estrutura ou o funcionamento dos sistemas na- turais em que elas se integram, de um modo que afecta a sua reprodução ou mesmo sobrevivência. Estes factores são alterações das características físicas, químicas ou biológicas dos habitats das espécies ou acções que causam mortalidade intencional ou acidental ou, ainda, a redução do sucesso reprodutor das espécies. Com esta edição, alcançou-se uma meta no processo de avaliação da fau- na de vertebrados de Portugal, remetendo-se para uma segunda etapa a avaliação das espécies de peixes marinhos e estuarinos. Tendo a clara noção da efemeridade da avaliação do risco de extinção suportada pelas condições e conhecimentos de um momento, espera-se que o Livro Vermelho seja um documento periodicamente actualizado. Finalmente, é elevada a expectativa de todos os que participaram na sua elaboração, de que este venha a contribuir decisivamente para um reforço da conservação das espécies ameaçadas em Portugal

Country-level gender inequality is associated with structural differences in the brains of women and men

男女間の不平等と脳の性差 --男女間の不平等は脳構造の性差と関連する--. 京都大学プレスリリース. 2023-05-10.Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality

Country-level gender inequality is associated with structural differences in the brains of women and men

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1