Prediction of individual genetic risk to prostate cancer using a polygenic score

BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. Prostate 75:1467–1474, 2015. © 2015 Wiley Periodicals, Inc.

Describing syntax with star-free regular expressions

Koskenniemen Äärellistilaisen leikkauskieliopin (FSIG) lauseopilliset rajoitteet ovat loogisesti vähemmän kompleksisia kuin mihin niissä käytetty formalismi vittaisi. Osoittautuukin että vaikka Voutilaisen (1994) englannin kielelle laatima FSIG-kuvaus käyttää useita säännöllisten lausekkeiden laajennuksia, kieliopin kuvaus kokonaisuutenaan palautuu äärelliseen yhdistelmään unionia, komplementtia ja peräkkäinasettelua. Tämä on oleellinen parannus ENGFSIG:n descriptiiviseen kompleksisuuteen. Tulos avaa ovia FSIG-kuvauksen loogisten ominaisuuksien syvemmälle analyysille ja FSIG kuvausten mahdolliselle optimoinnillle. Todistus sisältää uuden kaavan, joka kääntää Koskenniemien rajoiteoperaation ilman markkerimerkkejä.

Assessing GCM Convergence for India Using the Variable Convergence Score

General circulation models (GCMs) use transient climate simulations to predict climate conditions in the future. Coarse-grid resolutions and process uncertainties necessitate the use of downscaling models to simulate precipitation. However, in the downscaling models, with multiple GCMs now available, selecting an atmospheric variable from a particular model which is representative of the ensemble mean becomes an important consideration. The variable convergence score (VCS) provides a simple yet meaningful approach to address this issue, providing a mechanism to evaluate variables against each other with respect to the stability they exhibit in future climate simulations. In this study, VCS methodology is applied to 10 atmospheric variables of particular interest in downscaling precipitation over India and also on a regional basis. The nested bias-correction methodology is used to remove the systematic biases in the GCMs simulations, and a single VCS curve is developed for the entire country. The generated VCS curve is expected to assist in quantifying the variable performance across different GCMs, thus reducing the uncertainty in climate impact-assessment studies. The results indicate higher consistency across GCMs for pressure and temperature, and lower consistency for precipitation and related variables. Regional assessments, while broadly consistent with the overall results, indicate low convergence in atmospheric attributes for the Northeastern parts of India.

Sequential Monte Carlo computation of the score and observed information matrix in state-space models with application to parameter estimation

Sequential Monte Carlo (SMC) methods are popular computational tools for Bayesian inference in non-linear non-Gaussian state-space models. For this class of models, we propose SMC algorithms to compute the score vector and observed information matrix recursively in time. We propose two different SMC implementations, one with computational complexity $\mathcal{O}(N)$ and the other with complexity $\mathcal{O}(N^{2})$ where $N$ is the number of importance sampling draws. Although cheaper, the performance of the $\mathcal{O}(N)$ method degrades quickly in time as it inherently relies on the SMC approximation of a sequence of probability distributions whose dimension is increasing linearly with time. In particular, even under strong \textit{mixing} assumptions, the variance of the estimates computed with the $\mathcal{O}(N)$ method increases at least quadratically in time. The $\mathcal{O}(N^{2})$ is a non-standard SMC implementation that does not suffer from this rapid degrade. We then show how both methods can be used to perform batch and recursive parameter estimation.

Carga de trabalho de enfermeiros: uma análise do Nursing Activities Score (NAS)

Este estudo tem como objeto a carga de trabalho de enfermeiros que trabalham em unidades de cuidados semi-intensivos. Seu objetivo geral foi identificar e analisar a percepção dos enfermeiros de uma unidade semi-intensiva acerca do instrumento Nursing Activities Score - NAS, tendo como foco o conceito de carga de trabalho. Os objetivos específicos foram: identificar domínios do NAS considerados pelos enfermeiros como capazes de avaliar a carga de trabalho; identificar os itens que os enfermeiros consideram relevantes e manteriam no instrumento, os itens que excluiriam e os que acrescentariam; identificar itens que os enfermeiros consideram subdimensionados, para os quais aumentariam a pontuação, os superdimensionados, para os quais diminuiriam a pontuação; e, ao final, discutir implicações dessa avaliação para a organização do trabalho e seus impactos na saúde do trabalhador de enfermagem. Estudo de abordagem quantitativa do tipo descritivo exploratória, com breve aporte qualitativo, utilizando a triangulação metodológica. O local de estudo foi uma unidade de média complexidade com 35 leitos em um hospital privado do Rio de Janeiro. Participaram do estudo 28 enfermeiros e os dados foram coletados por meio de um questionário com perguntas fechadas e abertas no período de abril a maio de 2008. O tratamento dos dados foi realizado com apoio do software Excel, utilizando estatística descritiva. O material qualitativo foi organizado em categorias, usando elementos da Análise de Conteúdo Temática. Entre os domínios, verificou-se que os enfermeiros consideram o que mais avalia a carga real de trabalho o Suporte Ventilatório, com 89%, e o domínio que não avalia a carga de trabalho foi o Suporte Neurológico, com 25%. Os três domínios mais citados para serem acrescidos de atividades foram o Suporte Renal, com 25%, seguido Intervenção Especificas, com 21%, e Suporte Metabólico, respectivamente. Quanto à exclusão de atividades, só dois domínios foram mencionados: Suporte Ventilatório, com 25%, e Atividade Básica, com 21%. Os enfermeiros acham que 69% da pontuação era adequada aos itens e 31% acreditam não estar adequada. No grupo, 27% aumentariam a pontuação em alguns itens e 4% diminuiriam a pontuação. Sobre a mensuração da carga de trabalho, acreditam que essa colabora no processo de trabalho, 79%, e 57% acham que mensurar a carga de trabalho através do NAS pode auxiliar na preservação de sua saúde. Concluímos que esse instrumento mensura a carga de trabalho na opinião dos enfermeiros, mas precisa ser adaptado à realidade da unidade onde está sendo aplicada. Além disso, os enfermeiros alteraram mais os itens relacionados à carga física sem identificar a carga psíquica de trabalho como relevante, evidenciando que o trabalho de enfermagem precisa ser mais bem conhecido pelos enfermeiros no que se refere às dimensões de impacto na sua saúde.

Tradução, adaptação cultural e validação do Nonarthritic Hip Score para o Brasil

A avaliação da qualidade de vida tem sido cada vez mais utilizada pelos profissionais da área de saúde para mensurar o impacto de doenças na vida dos pacientes, bem como para avaliar os resultados dos tratamentos realizados. O crescente interesse por protocolos de pesquisa clínica em doenças não degenerativas do quadril tem encontrado muitos obstáculos na avaliação objetiva de seus resultados, principalmente nos estudos de observação de novas intervenções terapêuticas, como a artroscopia. O Nonarthritic Hip Score (NAHS) é um instrumento de avaliação clínica, desenvolvido originalmente em inglês, cujo objetivo é avaliar a função da articulação do quadril em pacientes jovens e fisicamente ativos. O objetivo desse estudo foi traduzir esse instrumento para a língua portuguesa, adaptá-lo para a cultura brasileira e validá-lo para que possa ser utilizado na avaliação de qualidade de vida de pacientes brasileiros com dor no quadril, sem doença degenerativa. A metodologia utilizada é a sugerida por Guillemin et al. (1993) e revisado por Beaton et al. (2000), que propuseram um conjunto de instruções padronizadas para adaptação cultural de instrumentos de qualidade de vida, incluindo cinco etapas: tradução, tradução de volta, revisão pelo comitê, pré-teste e teste, com reavaliação dos pesos dos escores, se relevante. A versão de consenso foi aplicada em 30 indivíduos. As questões sobre atividades esportivas e tarefas domésticas foram modificadas, para melhor adaptação à cultura brasileira. A versão brasileira do Nonarthritic Hip Score (NAHS-Brasil) foi respondida por 64 pacientes com dor no quadril, a fim de avaliar as propriedades de medida do instrumento: reprodutibilidade, consistência interna e validade. A reprodutibilidade foi 0,9, mostrando uma forte correlação; a consistência interna mostrou correlação entre 0,8 e 0,9, considerada boa e excelente; a validade foi considerada respectivamente boa e excelente; a correlação entre NAHS-Brasil e WOMAC foi 0,9; e a correlação entre o NAHS-Brasil e Questionário Algofuncional de Lequesne foi 0,79. O Nonarthritic Hip Score foi traduzido para a língua portuguesa e adaptado à cultura brasileira, de acordo com o conjunto de instruções padronizadas para adaptação cultural de instrumentos de qualidade de vida. Sua reprodutibilidade, consistência interna e validade foram também demonstradas.

Predictive score for mortality in patients with COPD exacerbations attending hospital emergency departments

Background: Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED). Such information could help stratify these patients and guide medical decision-making. The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit. Methods: This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals. Recruitment started in June 2008 and ended in September 2010. Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up. Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit. Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample. The score was compared with other published prediction rules for patients with stable COPD. Results: In total, 2,487 patients were included in the study. Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85). Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model. The same variables were predictors of death at 1 month (AUC = 0.85). Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better. Conclusions: Five clinical predictors easily available in the ED, and also in the primary care setting, can be used to create a simple and easily obtained score that allows clinicians to stratify patients with eCOPD upon ED arrival and guide the medical decision-making process.

The use of syntax and multiple alternatives in the VODIS voice operated database inquiry system

The paper describes the architecture of VODIS, a voice operated database inquiry system, and presents some experiments which investigate the effects on performance of varying the level of a priori syntactic constraints. The VODIS system includes a novel mechanism for incorporating context-free grammatical constraints directly into the word recognition algorithm. This allows the degree of a priori constraint to be smoothly varied and provides for the controlled generation of multiple alternatives. The results show that when the spoken input deviates from the predefined task grammar, a combination of weak a priori syntax rules in conjunction with full a posteriori parsing on a lattice of alternative word matches provides the most robust recognition performance. © 1991.

Evaluation of quality of shark livers using bio-chemical properties and organoleptic score sheet

Shark livers are considered as an important raw material providing a quality fish oil. It has been reported to aid white — blood-cell production and act as an active ingredient in hemorrhoid treatments. It is also reported that liver oil as a good supplement of vitamin A and poly-unsaturated fatty acids which are important to the development of brain cells in human. Freshness of livers is very important to extract better quality oil. In Sri Lanka, the annual shark production amounts to 8000t, however the quality of livers collected from landing sites has not being measured yet. Present study was conducted to evaluate the quality of silky (Charcarninus fakiformis) shark livers available in Negombo and Beruwala landing sites in the West Coast of Sri Lanka and also to study the relationship between organoleptic and bio-chemical correlation on freshness of shark livers. Liver samples which were collected from landing sites in the West coast of Sri Lanka, were evaluated for external and internal colour, texture and odour. Total volatile nitrogen (TVN), pH value, free fatty acid (FFA%) and peroxide (PV) values of livers were also determined to assess quality. According to the organoleptic scoring system 4.3% of liver samples were categorized as best in quality while 30.4%, 56.5% and 8.7% rated as good, medium and poor in quality respectively at the Negombo and Beruwala landing sites. Bio-chemical analysis showed that the better quality livers had the highest score for sensory evaluation and low values for TVN, FFA and peroxide value while low quality livers gave low score for sensory evaluation and high TVN, FFA, peroxide values. Correlation coefficient of organoleptic scores against total volatile nitrogen value, pH value, free fatty acid % and peroxide value of shark livers were determined by statistical analysis. Organoleptic score of shark livers was found to be highly.