Mayaro Virus Infection in Amazonia: A Multimodel Inference Approach to Risk Factor Assessment

Background: Arboviral diseases are major global public health threats. Yet, our understanding of infection risk factors is, with a few exceptions, considerably limited. A crucial shortcoming is the widespread use of analytical methods generally not suited for observational data - particularly null hypothesis-testing (NHT) and step-wise regression (SWR). Using Mayaro virus (MAYV) as a case study, here we compare information theory-based multimodel inference (MMI) with conventional analyses for arboviral infection risk factor assessment. Methodology/Principal Findings: A cross-sectional survey of anti-MAYV antibodies revealed 44% prevalence (n = 270 subjects) in a central Amazon rural settlement. NHT suggested that residents of village-like household clusters and those using closed toilet/latrines were at higher risk, while living in non-village-like areas, using bednets, and owning fowl, pigs or dogs were protective. The "minimum adequate" SWR model retained only residence area and bednet use. Using MMI, we identified relevant covariates, quantified their relative importance, and estimated effect-sizes (beta +/- SE) on which to base inference. Residence area (beta(Village) = 2.93 +/- 0.41; beta(Upland) = -0.56 +/- 0.33, beta(Riverbanks) = -2.37 +/- 0.55) and bednet use (beta = -0.95 +/- 0.28) were the most important factors, followed by crop-plot ownership (beta = 0.39 +/- 0.22) and regular use of a closed toilet/latrine (beta = 0.19 +/- 0.13); domestic animals had insignificant protective effects and were relatively unimportant. The SWR model ranked fifth among the 128 models in the final MMI set. Conclusions/Significance: Our analyses illustrate how MMI can enhance inference on infection risk factors when compared with NHT or SWR. MMI indicates that forest crop-plot workers are likely exposed to typical MAYV cycles maintained by diurnal, forest dwelling vectors; however, MAYV might also be circulating in nocturnal, domestic-peridomestic cycles in village-like areas. This suggests either a vector shift (synanthropic mosquitoes vectoring MAYV) or a habitat/habits shift (classical MAYV vectors adapting to densely populated landscapes and nocturnal biting); any such ecological/adaptive novelty could increase the likelihood of MAYV emergence in Amazonia.

Assessment of variance components in nonlinear mixed-effects elliptical models

The issue of assessing variance components is essential in deciding on the inclusion of random effects in the context of mixed models. In this work we discuss this problem by supposing nonlinear elliptical models for correlated data by using the score-type test proposed in Silvapulle and Silvapulle (1995). Being asymptotically equivalent to the likelihood ratio test and only requiring the estimation under the null hypothesis, this test provides a fairly easy computable alternative for assessing one-sided hypotheses in the context of the marginal model. Taking into account the possible non-normal distribution, we assume that the joint distribution of the response variable and the random effects lies in the elliptical class, which includes light-tailed and heavy-tailed distributions such as Student-t, power exponential, logistic, generalized Student-t, generalized logistic, contaminated normal, and the normal itself, among others. We compare the sensitivity of the score-type test under normal, Student-t and power exponential models for the kinetics data set discussed in Vonesh and Carter (1992) and fitted using the model presented in Russo et al. (2009). Also, a simulation study is performed to analyze the consequences of the kurtosis misspecification.

Cointegration: Bayesian Significance Test

To estimate causal relationships, time series econometricians must be aware of spurious correlation, a problem first mentioned by Yule (1926). To deal with this problem, one can work either with differenced series or multivariate models: VAR (VEC or VECM) models. These models usually include at least one cointegration relation. Although the Bayesian literature on VAR/VEC is quite advanced, Bauwens et al. (1999) highlighted that "the topic of selecting the cointegrating rank has not yet given very useful and convincing results". The present article applies the Full Bayesian Significance Test (FBST), especially designed to deal with sharp hypotheses, to cointegration rank selection tests in VECM time series models. It shows the FBST implementation using both simulated and available (in the literature) data sets. As illustration, standard non informative priors are used.

Comparing non-stationary and irregularly spaced time series

In this paper, we present approximate distributions for the ratio of the cumulative wavelet periodograms considering stationary and non-stationary time series generated from independent Gaussian processes. We also adapt an existing procedure to use this statistic and its approximate distribution in order to test if two regularly or irregularly spaced time series are realizations of the same generating process. Simulation studies show good size and power properties for the test statistic. An application with financial microdata illustrates the test usefulness. We conclude advocating the use of these approximate distributions instead of the ones obtained through randomizations, mainly in the case of irregular time series. (C) 2012 Elsevier B.V. All rights reserved.

Coping Style and Depressive Symptomatology during Pregnancy in a Private Setting Sample

Aim: to evaluate the association of antenatal depressive symptomatology (AD) with life events and coping styles, the hypothesis was that certain coping strategies are associated to depressive symptomatology. Methods: we performed a cross sectional study of 312 women attending a private clinic in the city of Osasco, Sao Paulo from 27/05/1998 to 13/05/2002. The following instruments were used: Beck Depression Inventory (BDI), Holmes and Rahe Schedule of Recent Events (SSRS), Folkman and Lazarus Ways of Coping Questionnaire and questionnaire with social-demographic and obstetric data. Inclusion criteria: women with 110 past history of depression, psychiatric treatment, alcohol or drug abuse and no clinical-obstetrical complications. Odds ratios and 95% CI were used to examine the association between AD (according to BDI) and exposures variables. Hypothesis testing was done with chi(2) tests and a p value < .05. Results: AD occurred in 21.1% of pregnant women. By the univariate analyses, education, number of pregnancies, previous abortion, husband income, situation of marriage and score of SSRS were associated with AD. All coping styles were associated with AD, except seeking support and positive reappraisal. By the multivariate analyses, four coping styles were kept in the final model: confront (p = .039), accepting responsibility (p < .001), escape-avoidance (p = .002), problem-solving (p = .005). Conclusions: AD was highly prevalent and was associated with maladaptive coping styles.

Schizophrenia, brain disease and meta-analyses: Integrating the pieces and testing Fusar-Poli`s hypothesis

This paper aims to discuss and test the hypothesis raised by Fusar-Poli [Fusar-Poli P. Can neuroimaging prove that schizophrenia is a brain disease? A radical hypothesis. Medical Hypotheses in press, corrected proof] that ""on the basis of the available imaging literature there is no consistent evidence to reject the radical and provocative hypothesis that schizophrenia is not a brain disease"". To achieve this goal, all meta-analyses on `fMRI and schizophrenia` published during the current decade and indexed in Pubmed were summarized, as much as some other useful information, e.g., meta-analyses on genetic risk factors. Our main conclusion is that the literature fully supports the hypothesis that schizophrenia is a syndrome (not a disease) associated with brain abnormalities, despite the fact that there is no singular and reductionist pathway from the nosographic entity (schizophrenia) to its causes. This irreducibility is due to the fact that the syndrome has more than one dimension (e.g., cognitive, psychotic and negative) and each of them is related to abnormalities in specific neuronal networks. A psychiatric diagnosis is a statistical procedure; these dimensions are not identically represented in each diagnosticated case and this explains the existence of more than one pattern of brain abnormalities related to schizophrenia. For example, chronification is associated with negativism while the first psychotic episode is not; in that sense, the same person living with schizophrenia may reveal different symptoms and fMRI patterns along the course of his life, and this is precisely what defines schizophrenia since the time when it was called Dementia Praecox (first by pick then by Kraepelin). It is notable that 100% of the collected meta-analyses on `fMRI and schizophrenia` reveal positive findings. Moreover, all meta-analyses that found positive associations between schizophrenia and genetic risk factors have to do with genes (SNPs) especially activated in neuronal tissue of the central nervous system (CNS), suggesting that, to the extent these polymorphisms are related to schizophrenia`s etiology, they are also related to abnormal brain activity. (C) 2009 Elsevier Ltd. All rights reserved.

Testing allele homogeneity: the problem of nested hypotheses

Background: The evaluation of associations between genotypes and diseases in a case-control framework plays an important role in genetic epidemiology. This paper focuses on the evaluation of the homogeneity of both genotypic and allelic frequencies. The traditional test that is used to check allelic homogeneity is known to be valid only under Hardy-Weinberg equilibrium, a property that may not hold in practice. Results: We first describe the flaws of the traditional (chi-squared) tests for both allelic and genotypic homogeneity. Besides the known problem of the allelic procedure, we show that whenever these tests are used, an incoherence may arise: sometimes the genotypic homogeneity hypothesis is not rejected, but the allelic hypothesis is. As we argue, this is logically impossible. Some methods that were recently proposed implicitly rely on the idea that this does not happen. In an attempt to correct this incoherence, we describe an alternative frequentist approach that is appropriate even when Hardy-Weinberg equilibrium does not hold. It is then shown that the problem remains and is intrinsic of frequentist procedures. Finally, we introduce the Full Bayesian Significance Test to test both hypotheses and prove that the incoherence cannot happen with these new tests. To illustrate this, all five tests are applied to real and simulated datasets. Using the celebrated power analysis, we show that the Bayesian method is comparable to the frequentist one and has the advantage of being coherent. Conclusions: Contrary to more traditional approaches, the Full Bayesian Significance Test for association studies provides a simple, coherent and powerful tool for detecting associations.

A comparative evaluation of polymerization stress data obtained with four different mechanical testing systems

Objectives. The null hypothesis was that mechanical testing systems used to determine polymerization stress (sigma(pol)) would rank a series of composites similarly. Methods. Two series of composites were tested in the following systems: universal testing machine (UTM) using glass rods as bonding substrate, UTM/acrylic rods, "low compliance device", and single cantilever device ("Bioman"). One series had five experimental composites containing BisGMA:TEGDMA in equimolar concentrations and 60, 65, 70, 75 or 80 wt% of filler. The other series had five commercial composites: Filtek Z250 (3M ESPE), Filtek A110 (3M ESPE), Tetric Ceram (Ivoclar), Heliomolar (Ivoclar) and Point 4 (Kerr). Specimen geometry, dimensions and curing conditions were similar in all systems. sigma(pol) was monitored for 10 min. Volumetric shrinkage (VS) was measured in a mercury dilatometer and elastic modulus (E) was determined by three-point bending. Shrinkage rate was used as a measure of reaction kinetics. ANOVA/Tukey test was performed for each variable, separately for each series. Results. For the experimental composites, sigma(pol) decreased with filler content in all systems, following the variation in VS. For commercial materials, sigma(pol) did not vary in the UTM/acrylic system and showed very few similarities in rankings in the others tests system. Also, no clear relationships were observed between sigma(pol) and VS or E. Significance. The testing systems showed a good agreement for the experimental composites, but very few similarities for the commercial composites. Therefore, comparison of polymerization stress results from different devices must be done carefully. (c) 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Testing the influence of far-field topographic forcing on subduction initiation at a passive margin

Despite favourable gravitational instability and ridge-push, elastic and frictional forces prevent subduction initiation fromarising spontaneously at passive margins. Here,we argue that forces arising fromlarge continental topographic gradients are required to initiate subduction at passivemargins. In order to test this hypothesis,we use 2Dnumerical models to assess the influence of the Andean Plateau on stressmagnitudes and deformation patterns at the Brazilian passive margin. The numerical results indicate that “plateau-push” in this region is a necessary additional force to initiate subduction. As the SE Brazilianmargin currently shows no signs of self-sustained subduction, we examined geological and geophysical data to determine if themargin is in the preliminary stages of subduction initiation. The compiled data indicate that the margin is presently undergoing tectonic inversion, which we infer as part of the continental–oceanic overthrusting stage of subduction initiation. We refer to this early subduction stage as the “Brazilian Stage”, which is characterized by N10 kmdeep reverse fault seismicity at themargin, recent topographic uplift on the continental side, thick continental crust at themargin, and bulging on the oceanic side due to loading by the overthrusting continent. The combined results of the numerical simulations and passivemargin analysis indicate that the SE Brazilian margin is a prototype candidate for subduction initiation.