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.

Local power properties of some asymptotic tests in symmetric linear regression models

In this paper we obtain asymptotic expansions, up to order n(-1/2) and under a sequence of Pitman alternatives, for the nonnull distribution functions of the likelihood ratio, Wald, score and gradient test statistics in the class of symmetric linear regression models. This is a wide class of models which encompasses the t model and several other symmetric distributions with longer-than normal tails. The asymptotic distributions of all four statistics are obtained for testing a subset of regression parameters. Furthermore, in order to compare the finite-sample performance of these tests in this class of models, Monte Carlo simulations are presented. An empirical application to a real data set is considered for illustrative purposes. (C) 2011 Elsevier B.V. All rights reserved.

Aerobic power in child, cadet and senior judo athletes

The aim of the present study was to compare performance and physiological responses during arm and leg aerobic power tests of combat duration in male child, cadet and senior judo athletes. Power output and physiological parameters, i.e., peak oxygen uptake ((V)over dotO(2)peak), peak ventilation, peak heart rate, lactate, and rate of perceived exertion, of 7 child (under 15 years: age class U15, 12.7 +/- 1.1 yrs), 10 cadet (U17, 14.9 +/- 0.7 yrs) and 8 senior (+20, 29.3 +/- 9.2 yrs) male judo athletes were assessed during incremental tests of combat duration on an arm crank and a cycle ergometer. Children as well as cadets demonstrated higher upper body relative VO(2)peak than seniors (37.3 +/- 4.9, 39.2 +/- 5.0 and 31.0 +/- 2.1 ml.kg(-1).min(-1), respectively); moreover, upper and lower body relative VO(2)peak decreased with increasing age (r = -0.575, p < 0.003 and r = -0.580, p < 0.002, respectively). Children showed lower blood lactate concentrations after cranking as well as after cycling when compared to seniors (7.8 +/- 2.4 vs. 11.4 +/- 2.1 mmol.l(-1) and 7.9 +/- 3.0 vs. 12.0 +/- 1.9 mmol.l(-1), respectively); furthermore, blood lactate values after cranking increased with age (r = 0.473, p < 0.017). These differences should be considered in planning the training for judo athletes of different age classes.

Gametic phase disequilibrium between the syntenic multiallelic HTG4 and HMS3 markers widely used for parentage testing in Thoroughbred horses

Validation of parentage and horse breed registries through DNA typing relies on estimates of random match probabilities with DNA profiles generated from multiple polymorphic loci. Of the twenty-seven microsatellite loci recommended by the International Society for Animal Genetics for parentage testing in Thoroughbred horses, eleven are located on five chromosomes. An important aspect in determining combined exclusion probabilities is the ascertainment of the genetic linkage status of syntenic markers, which may affect reliable use of the product rule in estimating random match probabilities. In principle, linked markers can be in gametic phase disequilibrium (GD). We aimed at determining the extent, by frequency and strength, of GD between the HTG4 and HMS3 multiallelic loci, syntenic on chromosome 9. We typed the qualified offspring (n (1) = 27; n (2) = 14) of two Quarter Bred stallions (registered by the Brazilian Association of Quarter Horse Breeders) and 121 unrelated horses from the same breed. In the 41 informative meioses analyzed, the frequency of recombination between the HTG4 and HMS3 loci was 0.27. Consistent with genetic map distances, this recombination rate does not fit to the theoretical distribution for independently segregated markers. We estimated sign-based D' coefficients as a measure of GD, and showed that the HTG4 and HMS3 loci are in significant, yet partial and weak, disequilibrium, with two allele pairs involved (HTG4*M/HMS3*P, D'(+) = 0.6274; and HTG4*K/HMS3*P, D'(-) = -0.6096). These results warn against the inadequate inclusion of genetically linked markers in the calculation of combined power of discrimination for Thoroughbred parentage validation.

Local power and size properties of the LR, Wald, score and gradient tests in dispersion models

We derive asymptotic expansions for the nonnull distribution functions of the likelihood ratio, Wald, score and gradient test statistics in the class of dispersion models, under a sequence of Pitman alternatives. The asymptotic distributions of these statistics are obtained for testing a subset of regression parameters and for testing the precision parameter. Based on these nonnull asymptotic expansions, the power of all four tests, which are equivalent to first order, are compared. Furthermore, in order to compare the finite-sample performance of these tests in this class of models, Monte Carlo simulations are presented. An empirical application to a real data set is considered for illustrative purposes. (C) 2012 Elsevier B.V. All rights reserved.

A holistic approach to model-based testing of Web service compositions

The behavior of composed Web services depends on the results of the invoked services; unexpected behavior of one of the invoked services can threat the correct execution of an entire composition. This paper proposes an event-based approach to black-box testing of Web service compositions based on event sequence graphs, which are extended by facilities to deal not only with service behavior under regular circumstances (i.e., where cooperating services are working as expected) but also with their behavior in undesirable situations (i.e., where cooperating services are not working as expected). Furthermore, the approach can be used independently of artifacts (e.g., Business Process Execution Language) or type of composition (orchestration/choreography). A large case study, based on a commercial Web application, demonstrates the feasibility of the approach and analyzes its characteristics. Test generation and execution are supported by dedicated tools. Especially, the use of an enterprise service bus for test execution is noteworthy and differs from other approaches. The results of the case study encourage to suggest that the new approach has the power to detect faults systematically, performing properly even with complex and large compositions. Copyright © 2012 John Wiley & Sons, Ltd.