Association Between Increased Mortality and Mild Thyroid Dysfunction in Cardiac Patients

BACKGROUND: The effects of subclinical thyroid dysfunction on cardiac outcome are not well defined. METHODS: To assess the relationship between mild thyroid dysfunction and the incidence of death in cardiac patients, we evaluated 3121 cardiac patients. Cardiac and overall deaths were considered. Four groups were defined: euthyroidism, subclinical hypothyroidism (SCH), subclinical hyperthyroidism (SCT), and low triiodothyronine syndrome (low T3). RESULTS: After mean follow-up of 32 months, there were 65 and 140 cardiac and overall deaths (3.4% and 7.3%), respectively, in euthyroidism, 15 and 27 (7.2% and 13.0%) in SCH, 8 and 9 (8.2% and 9.2%) in SCT, and 59 and 119 (6.5% and 13.1%) in low T3. Survival rates for cardiac death were lower in SCH, SCT, and low T3 than in euthyroidism (log-rank test; chi2 = 19.46; P < .001). Survival rates for overall death were lower in SCH and low T3 than in euthyroidism (log-rank test; chi2 = 26.67; P < .001). After adjustment for several risk factors, hazard ratios (HRs) for cardiac death were higher in SCH (HR, 2.40; 95% confidence interval [CI], 1.36-4.21; P = .02), SCT (HR, 2.32; 95% CI, 1.11-4.85; P = .02), and low T(3) (HR, 1.63; 95% CI, 1.14-2.33; P = .007) than in euthyroidism; HRs for overall death were higher in SCH (HR, 2.01; 95% CI, 1.33-3.04; P < .001) and low T3 (HR, 1.57; 95% CI, 1.22-2.01; P < .001) but not in SCT. CONCLUSION: A mildly altered thyroid status is associated with an increased risk of mortality in patients with cardiac disease

Nonlinear Parabolic Equations arising in Mathematical Finance

This survey paper is focused on qualitative and numerical analyses of fully nonlinear partial differential equations of parabolic type arising in financial mathematics. The main purpose is to review various non-linear extensions of the classical Black-Scholes theory for pricing financial instruments, as well as models of stochastic dynamic portfolio optimization leading to the Hamilton-Jacobi-Bellman (HJB) equation. After suitable transformations, both problems can be represented by solutions to nonlinear parabolic equations. Qualitative analysis will be focused on issues concerning the existence and uniqueness of solutions. In the numerical part we discuss a stable finite-volume and finite difference schemes for solving fully nonlinear parabolic equations.Comment: arXiv admin note: substantial text overlap with arXiv:1603.0387

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

A universidade, a escola e as necessidades especiais: como melhorar? Como contribuir?

Um dos principais objetivos de qualquer programa educacional de governo é educar os cidadãos para serem comprometidos com toda asociedade. Para garantir o acesso a todos à educação, os professores precisam atender com qualidade todos os alunos, inclusive aqueles comnecessidades especiais. No entanto, a falta de informação e formação profissional continua sendo ainda um dos principais obstáculos paraalcançar este objetivo. A Escola de Inclusão é um programa de extensão de uma universidade federal brasileira e aborda diferentes áreas(ex: direitos humanos, educação e saúde), estimulando a interação de professores e licenciandos. Seus objetivos incluem a produção demateriais de ensino inclusivos e tecnologia educacional, a formação continuada de professores e a criação de conhecimento e de condiçõesde acessibilidade para os alunos com necessidades especiais. Neste trabalho o nosso objetivo foi analisar brevemente a estratégia deste programaque considera os profissionais de educação, os estudantes de graduação (licenciandos) e alunos com necessidades especiais, comoo melhor público para a construção e/ou avaliação do seu material didático. Interessantemente, a nossa análise qualitativa sobre os relatosde professores, alunos de graduação e um estudante do ensino médio cego, que participaram de edições desse programa, reforçam queprojetos de universidades podem ser capazes de contribuir para a formação de profissionais, de alunos de graduação e de ensino médio,enquanto aproximam o público-alvo da perspectiva do professor. Esta iniciativa também sugere que os alunos com necessidades especiaispodem participar ativamente de sua própria educação se as instituições aprenderem a estimulá-los a um comportamento pró-ativo

A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism

Prenatal experience with language shapes the brain

Human infants acquire language with notable ease compared to adults, but the neural basis of their remarkable brain plasticity for language remains little understood. Applying a scaling analysis of neural oscillations to address this question, we show that newborns' electrophysiological activity exhibits increased long-range temporal correlations after stimulation with speech, particularly in the prenatally heard language, indicating the early emergence of brain specialization for the native language.</p

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Prediction and clinical utility of a contralateral breast cancer risk model

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