Multivariate Generalized Linear Models for Twin and Family Data.

Multivariate twin and family studies are one of the most important tools to assess diseases inheritance as well as to study their genetic and environment interrelationship. The multivariate analysis of twin and family data is in general based on structural equation modelling or linear mixed models that essentially decomposes sources of covariation as originally suggested by  Fisher. In this paper, we propose a flexible and unified statistical modelling framework for analysing multivariate Gaussian and non-Gaussian twin and family data. The non-normality is taken into account by actually modelling the mean and variance relationship, while the covariance structure is modelled by means of a linear covariance model including the option to model the dispersion components as functions of known covariates in a regression model fashion. The marginal specification of our models allows us to extend classic models and biometric indices such as the bivariate heritability, genetic, environmental and phenotypic correlations to non-Gaussian data. We illustrate the proposed models through simulation studies and six data analyses and provide computational implementation in R through the package mglm4twin.

Inherited and Acquired Determinants of Hepatic CYP3A Activity in Humans.

Human CYP3A enzymes (including CYP3A4 and CYP4A5) metabolize about 40% of all drugs and numerous other environmental and endogenous substances. CYP3A activity is highly variable within and between humans. As a consequence, therapy with standard doses often results in too low or too high blood and tissue concentrations resulting in therapeutic failure or dose-related adverse reactions. It is an unanswered question how much of the big interindividual variation in CYP3A activity is caused by genetic or by environmental factors. This question can be answered by the twin study approach. Using midazolam as CYP3A probe drug, we studied 43 monozygotic and 14 dizygotic twins and measured midazolam and its metabolite 1-OH-midazolam. In addition, endogenous biomarkers of CYP3A activity, 4ß-OH-cholesterol and 6ß-OH-cortisol, were analyzed. Additive genetic effects accounted for only 15% of the variation in midazolam AUC, whereas 48% was attributed to common environmental factors. In contrast, 73, 56, and 31% of 1-OH-midazolam, 4ß-OH-cholesterol and 6ß-OH-cortisol variation was due to genetic effects. There was a low phenotypic correlation between the four CYP3A biomarkers. Only between midazolam and its 1-OH-metabolite, and between midazolam and 6ß-OH-cortisol we found significant bivariate genetic correlations. Midazolam AUC differed depending on the CYP3A4∗22 variant (p = 0.001) whereas plasma 4ß-OH-cholesterol was significantly lower in homozygous carriers of CYP3A5∗3 (p = 0.02). Apparently, non-genomic factors played a dominant role in the inter-individual variation of the CYP3A probe drug midazolam. A small intra-individual pharmacokinetic variation after repeated administration of midazolam was rated earlier as indication of high heritability of CYP3A activity, but according to present data that could also largely be due to constant environmental factors and/or heritability of liver blood flow. The higher heritabilities of 4ß-OH-cholesterol and of 1-OH-midazolam may deserve further research on the underlying factors beyond CYP3A genes. Clinical Trial Registration: ClinicalTrials.gov: NCT01845194 and EUDRA-CT: 2008-006223-31.

Comparing Artificial Neural Network Architectures for Brazilian Stock Market Prediction.

Prediction of financial time series is a great challenge for statistical models. In general, the stock market times series present high volatility due to its sensitivity to economic and political factors. Furthermore, recently, the covid-19 pandemic has caused a drastic change in the stock exchange times series. In this challenging context, several computational techniques have been proposed to improve the performance of predicting such times series. The main goal of this article is to compare the prediction performance of five neural network architectures in predicting the six most traded stocks of the official Brazilian stock exchange B3 from March 2019 to April 2020. We trained the models to predict the closing price of the next day using as inputs its own previous values. We compared the predictive performance of multiple linear regression, Elman, Jordan, radial basis function, and multilayer perceptron architectures based on the root of the mean square error. We trained all models using the training set while hyper-parameters such as the number of input variables and hidden layers were selected using the testing set. Moreover, we used the trimmed average of 100 bootstrap samples as our prediction. Thus, our approach allows us to measure the uncertainty associate with the predicted values. The results showed that for all times series, considered all architectures, except the radial basis function, the networks tunning provide suitable fit, reasonable predictions, and confidence intervals.

Identifying traffic accident black spots with Poisson-Tweedie models.

This paper aims at the identification of black spots for traffic accidents, i.e. locations with accident counts beyond what is usual for similar locations, using spatially and temporally aggregated hospital records from Funen, Denmark. Specifically, we apply an autoregressive Poisson-Tweedie model, which covers a wide range of discrete distributions and handles zero-inflation as well as overdispersion. The estimated power parameter of the model was 1.6 (SE=0.06) suggesting a distribution close to the Pólya-Aeppli distribution. We identified nine black spots consistently standing out in all six considered calendar years and calculated by simulations a probability of p=0.03 for these to be chance findings. Altogether, our results recommend these sites for further investigation and suggest that our simple approach could play a role in future area based traffic accident prevention planning.

Transcultural adaptation and validation of the Conditions of Work Effectiveness-Questionnaire-II instrument.

OBJECTIVE: This study aims at translating and validating the content of the instrument Conditions of Work Effectiveness-Questionnaire-II CWEQ-II), developed by Laschinger, Finegan, Shamian and Wilk, modified from the original CWEQ for the Brazilian culture. METHOD: The methodological procedure consisted of the stages of translation of the instrument into the Portuguese language; back-translation; semantic, idiomatic and cultural equivalence and tests of the final version. The instrument in the Portuguese version was applied to a group of 40 nurses in two hospitals. RESULTS: The data resulted in a Cronbach's Alpha of 0.86 for the first hospital and 0.88 for the second one. The results of the factorial analysis are considered sufficiently satisfactory. CONCLUSION: It is to conclude that the instrument can be used in Brazil.

Transcultural adaptation and validation of the Conditions of Work Effectiveness - Questionnaire-II instrument / Adaptação transcultural e validação do instrumento Conditions of Work Effectiveness - Questionnaire-II / Adaptación transcultural y validez del instrumento Conditions of Work Effectiveness - Questionnaire-II

OBJECTIVE: This study aims at translating and validating the content of the instrument Conditions of Work Effectiveness - Questionnaire-II (CWEQ-II), developed by Laschinger, Finegan, Shamian and Wilk, modified from the original CWEQ for the Brazilian culture. METHOD: the methodological procedure consisted of the stages of translation of the instrument into the Portuguese language; back-translation; semantic, idiomatic and cultural equivalence and tests of the final version. The instrument in the Portuguese version was applied to a group of 40 nurses in two hospitals. RESULTS: the data resulted in a Cronbach's Alpha of 0.86 for the first hospital and 0.88 for the second one. The results of the factorial analysis are considered sufficiently satisfactory. CONCLUSION: It is to conclude that the instrument can be used in Brazil. .

OBJETIVO: este estudo teve como objetivo traduzir e validar o conteúdo do instrumento Conditions of Work Effectiveness - Questionnaire-II, desenvolvido por Laschinger, Finegan, Shamian e Wilk e modificado do original Conditions Work Effectiveness - Questionnaire, para a cultura brasileira. MÉTODO: o procedimento metodológico constituiu-se das etapas de tradução do instrumento para a língua portuguesa; back-translation; equivalência semântica, idiomática e cultural e testes da versão final. O instrumento na versão em português foi aplicado a um grupo de 40 enfermeiras, em dois hospitais. RESULTADOS: os dados resultaram em alfa de Cronbach em 0,86 para o primeiro hospital e 0,88 para o segundo. Os resultados da análise fatorial são considerados bastante satisfatórios. CONCLUSÃO: conclui-se que o instrumento pode ser utilizado no Brasil. .

OBJETIVO: este estudio tuvo como objetivo traducir y validar el contenido del instrumento Conditions of Work Effectiveness - Questionnaire-II (CWEQ-II), desarrollado por Laschinger, Finegan, Shamian y Wilk y modificado del original CWEQ, para la cultura brasileña. MÉTODO: el procedimiento metodológico se constituye de las etapas de traducción del instrumento para la lengua portuguesa; back-translation; equivalencia semántica, idiomática y cultural y pruebas de la versión final. El instrumento en la versión en portugués fue aplicado a un grupo de 40 enfermeras, en dos hospitales. RESULTADOS: los datos resultaron en Alfa de Cronbach en 0,86 para el primer hospital y 0,88 para el segundo. Los resultados del análisis de los factores son considerados muy satisfactorios. CONCLUSIÓN: se concluye que el instrumento puede ser utilizado en Brasil. .

Sustained reduction of the dengue vector population resulting from an integrated control strategy applied in two Brazilian cities.

Aedes aegypti has developed evolution-driven adaptations for surviving in the domestic human habitat. Several trap models have been designed considering these strategies and tested for monitoring this efficient vector of Dengue. Here, we report a real-scale evaluation of a system for monitoring and controlling mosquito populations based on egg sampling coupled with geographic information systems technology. The SMCP-Aedes, a system based on open technology and open data standards, was set up from March/2008 to October/2011 as a pilot trial in two sites of Pernambuco -Brazil: Ipojuca (10,000 residents) and Santa Cruz (83,000), in a joint effort of health authorities and staff, and a network of scientists providing scientific support. A widespread infestation by Aedes was found in both sites in 2008-2009, with 96.8%-100% trap positivity. Egg densities were markedly higher in SCC than in Ipojuca. A 90% decrease in egg density was recorded in SCC after two years of sustained control pressure imposed by suppression of >7,500,000 eggs and >3,200 adults, plus larval control by adding fishes to cisterns. In Ipojuca, 1.1 million mosquito eggs were suppressed and a 77% reduction in egg density was achieved. This study aimed at assessing the applicability of a system using GIS and spatial statistic analysis tools for quantitative assessment of mosquito populations. It also provided useful information on the requirements for reducing well-established mosquito populations. Results from two cities led us to conclude that the success in markedly reducing an Aedes population required the appropriate choice of control measures for sustained mass elimination guided by a user-friendly mosquito surveillance system. The system was able to support interventional decisions and to assess the program's success. Additionally, it created a stimulating environment for health staff and residents, which had a positive impact on their commitment to the dengue control program.