Bayesian Modeling for Epistasis Analysis Using Data-Driven Reversible Jump.

We propose a procedure for modeling a phenotype using QTLs which estimate the additive and dominance effects of genotypes and epistasis. The estimation of the model is implemented through a Bayesian approach which uses the data-driven reversible jump (DDRJ) for multiple QTL mapping and model selection. We compare the DDRJ's performance with the usual reversible jump (RJ), QTLBim, multiple interval mapping (MIM) and LASSO using real and simulated data sets. The DDRJ outperforms the available methods to estimate the number of QTLs in epistatic models and it identifies their locations in the genome, without increasing the number of false-positive QTLs in the considered data. Since QTL mapping is a regression model involving complex non-observable variables and their interactions, the model selection procedure proposed here is also useful in other areas of research. The application for identifying main and epistatic relevant QTLs to systolic blood pressure after salt intervention is our main motivation.

A new Bayesian approach for QTL mapping of family data.

In this paper, we propose a new Bayesian approach for QTL mapping of family data. The main purpose is to model a phenotype as a function of QTLs' effects. The model considers the detailed familiar dependence and it does not rely on random effects. It combines the probability for Mendelian inheritance of parents' genotype and the correlation between flanking markers and QTLs. This is an advance when compared with models which use only Mendelian segregation or only the correlation between markers and QTLs to estimate transmission probabilities. We use the Bayesian approach to estimate the number of QTLs, their location and the additive and dominance effects. We compare the performance of the proposed method with variance component and LASSO models using simulated and GAW17 data sets. Under tested conditions, the proposed method outperforms other methods in aspects such as estimating the number of QTLs, the accuracy of the QTLs' position and the estimate of their effects. The results of the application of the proposed method to data sets exceeded all of our expectations.

Bayesian Computational Methods for Sampling from the Posterior Distribution of a Bivariate Survival Model, Based on AMH Copula in the Presence of Right-Censored Data.

In this paper, we study the performance of Bayesian computational methods to estimate the parameters of a bivariate survival model based on the Ali-Mikhail-Haq copula with marginal distributions given by Weibull distributions. The estimation procedure was based on Monte Carlo Markov Chain (MCMC) algorithms. We present three version of the Metropolis-Hastings algorithm: Independent Metropolis-Hastings (IMH), Random Walk Metropolis (RWM) and Metropolis-Hastings with a natural-candidate generating density (MH). Since the creation of a good candidate generating density in IMH and RWM may be difficult, we also describe how to update a parameter of interest using the slice sampling (SS) method. A simulation study was carried out to compare the performances of the IMH, RWM and SS. A comparison was made using the sample root mean square error as an indicator of performance. Results obtained from the simulations show that the SS algorithm is an effective alternative to the IMH and RWM methods when simulating values from the posterior distribution, especially for small sample sizes. We also applied these methods to a real data set.

Improving Sample Distribution Homogeneity in Three-Dimensional Microfluidic Paper-Based Analytical Devices by Rational Device Design.

Paper-based devices are a portable, user-friendly, and affordable technology that is one of the best analytical tools for inexpensive diagnostic devices. Three-dimensional microfluidic paper-based analytical devices (3D-µPADs) are an evolution of single layer devices and they permit effective sample dispersion, individual layer treatment, and multiplex analytical assays. Here, we present the rational design of a wax-printed 3D-µPAD that enables more homogeneous permeation of fluids along the cellulose matrix than other existing designs in the literature. Moreover, we show the importance of the rational design of channels on these devices using glucose oxidase, peroxidase, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) reactions. We present an alternative method for layer stacking using a magnetic apparatus, which facilitates fluidic dispersion and improves the reproducibility of tests performed on 3D-µPADs. We also provide the optimized designs for printing, facilitating further studies using 3D-µPADs.

A generalized mixture model applied to diabetes incidence data.

We present a generalization of the usual (independent) mixture model to accommodate a Markovian first-order mixing distribution. We propose the data-driven reversible jump, a Markov chain Monte Carlo (MCMC) procedure, for estimating the a posteriori probability for each model in a model selection procedure and estimating the corresponding parameters. Simulated datasets show excellent performance of the proposed method in the convergence, model selection, and precision of parameters estimates. Finally, we apply the proposed method to analyze USA diabetes incidence datasets.

Development and statistical assessment of a paper-based immunoassay for detection of tumor markers.

Paper-based assays are an attractive low-cost option for clinical chemistry testing, due to characteristics such as short time of analysis, low consumption of samples and reagents, and high portability of assays. However, little attention has been given to the evaluation of the performance of these simple tests, which should include the use of a statistical approach to define the choice of best cut-off value for the test. The choice of the cut-off value impacts on the sensitivity and specificity of the bioassay. Here, we developed a paper-based immunoassay for the detection of the carcinoembryonic antigen (CEA) and performed a statistical assessment to establish the assay's cut-off value using the Youden's J index (68.28 A.U.), what allowed for a gain in sensibility (0.86) and specificity (1.0). We also discuss about the importance of defining a gray zone as a safety margin for test (±12% over the cut-off value), eliminating all false positives and false negatives outcomes and avoiding misleading results. The test accuracy was calculated as the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, presenting a value of 0.97, what classifies this test as highly accurate. We propose here a low-cost method capable of detecting carcinoembryonic antigen (CEA) in human serum samples, highlighting the importance of statistical tools to evaluate a new low-cost diagnostic method.

Data-Driven Reversible Jump for QTL Mapping.

We propose a birth-death-merge data-driven reversible jump (DDRJ) for multiple-QTL mapping where the phenotypic trait is modeled as a linear function of the additive and dominance effects of the unknown QTL genotypes. We compare the performance of the proposed methodology, usual reversible jump (RJ) and multiple-interval mapping (MIM), using simulated and real data sets. Compared with RJ, DDRJ shows a better performance to estimate the number of QTLs and their locations on the genome mainly when the QTLs effect is moderate, basically as a result of better mixing for transdimensional moves. The inclusion of a merge step of consecutive QTLs in DDRJ is efficient, under tested conditions, to avoid the split of true QTL's effects between false QTLs and, consequently, selection of the wrong model. DDRJ is also more precise to estimate the QTLs location than MIM in which the number of QTLs need to be specified in advance. As DDRJ is more efficient to identify and characterize QTLs with smaller effect, this method also appears to be useful and brings contributions to identifying single-nucleotide polymorphisms (SNPs) that usually have a small effect on phenotype.

Avaliação do limiar de anaerobiose obtido pela resposta da freqüência cardíaca e análise da sua variabilidade em protocolo de exercício físico dinâmico descontínuo em esteira rolante, em pacientes portadores de fator de risco e/ou doença cardiovascular instalada: estudo de 2 casos / Anaerobic threshold determination by heart rate response and heart rate variability analysis during a discontinuous dynamic physical exercise protocol at treadmill in two patients with risk factor and/or cardiovascular disease

Os objetivos deste estudo foram determinar o limiar de anaerobiose (LA), utilizando um teste de esforço físico dinâmico em degraus descontínuos (TEFDD) em esteira rolante, por meio da resposta da freqüência cardíaca (FC), analisar sua variabilidade (VFC), bem como verificar a adequação do protocolo de treinamento, baseado no LA. Dois homens, de 56 e 61 anos, portadores de fatores de risco e/ou doença cardiovascular instalada, foram submetidos ao TEFDD, que consistiu na realização de 4 velocidades distintas com duração de 6 minutos cada, a partir da qual foi determinado o LA por meio da aplicação de um modelo semiparamétrico aos dados de FC. Foram analisadas FC média e sua variabilidade, pelo índice temporal RMSSD dos intervalos R-R em milissegundos em cada velocidade avaliada. A partir dos resultados verificamos que a metodologia utilizada foi adequada para identificação do LA e que o protocolo de treinamento de ambos voluntários estava sendo realizado na faixa do LA. Também foi possível observar que em intensidades mais elevadas de exercício ocorreu um predomínio da atividade simpática sobre o coração, a qual é evidenciada pelo aumento da FC juntamente com a redução da VFC.

The purposes of present study were determine the anaerobic threshold (AT) by heart rate (HR) response and analyze the heart rate variability (VFC) during a discontinuous dynamic physical exercise protocol (DDPEP) at treadmill and, additionally, verify if the training performed by the subjects is adequate when the LA is considered. Two 56 and 61 years-old men, with risk factor and/or cardiovascular disease, performed a DDPEP at a treadmill. This protocol was constituted by 4 different velocities with 6 minutes duration in which a semi parametric model was applied to determine the AT. In each velocity, the average of HR and HRV, which was analyzed by the RMSSD index of R-R intervals in milliseconds, were calculated. The results suggest that the method utilized was adequate to AT determination, confirming that the training performed by the subjects was realized at intensities close to the AT. In addition, a predominance of sympathetic activity on the heart was observed at the higher efforts intensities which was confirmed by increased HR and decreased HRV.

Opiniöes da populaçäo urbana de Säo Carlos sobre um programa radiofônico de comunicaçäo em saúde

Foi realizado um inquérito em uma amostra da populaçäo urbana de Säo Carlos - SP, tendo sido visitado 504 domicílios no período de abril a junho de 1989. Os dados referentes a 2104 pessoas destes domicílios foram coletados com o objetivo de se conhecer os hábitos quanto aos meios de comunicaçäo de massa, televisäo, rádio FM e AM, bem como o interesse por programas radiofônicos de saúde. Verificou-se que a televisäo é o meio de comunicaçäo com maior audiência sendo que o nível aumenta consideravelmente no período que vai das 19:00 horas às 23:00 horas. Para as crianças o nível de audiência de televisäo assumem dois grandes períodos do dia; manhä e tarde. O rádio FM é preferido pelos jovens sendo que a curva de audiência é constante das 8:00 horas da manhä até mais ou menos 19:00 horas. Rádio AM tem seu pico de audiência no período da manhä principalmente das 7:00 às 8:00 horas. A populaçäo mostrou interesse por programas de saúde em rádio, obtendo-se respostas afirmativas em 92,7% dos entrevistados. Definiram também horários de preferência e os temas de maior interesse.