The Effect of Branch Length Variation on the Selection of Models of Molecular Evolution

Models of sequence evolution play an important role in molecular evolutionary studies. The use of inappropriate models of evolution may bias the results of the analysis and lead to erroneous conclusions. Several procedures for selecting the best-fit model of evolution for the data at hand have been proposed, like the likelihood ratio test (LRT) and the Akaike (AIC) and Bayesian (BIC) information criteria. The relative performance of these model-selecting algorithms has not yet been studied under a range of different model trees. In this study, the influence of branch length variation upon model selection is characterized. This is done by simulating sequence alignments under a known model of nucleotide substitution, and recording how often this true model is recovered by different model-fitting strategies. Results of this study agree with previous simulations and suggest that model selection is reasonably accurate. However, different model selection methods showed distinct levels of accuracy. Some LRT approaches showed better performance than the AIC or BIC information criteria. Within the LRTs, model selection is affected by the complexity of the initial model selected for the comparisons, and only slightly by the order in which different parameters are added to the model. A specific hierarchy of LRTs, which starts from a simple model of evolution, performed overall better than other possible LRT hierarchies, or than the AIC or BIC. Received: 2 October 2000 / Accepted: 4 January 2001     

Neurobehavioral Dysfunction as a Possible Sentinel of Methylmercury Exposure

The main concern regarding methylmercury neurotoxicity relates to adverse effects on the brain during development. Many environmental chemicals may act as developmental neurotoxicants, but solid documentation from epidemiological studies exists only on methylmercury, lead, and polychlorinated biphenyls (PCBs). Neurobehavioral tests may reveal subtle dysfunctions, but the tests chosen must be valid and appropriate for the setting. In a prospective study in the Faroe Islands, the main neuropsychological functions affected by prenatal methylmercury exposure were attention, language and memory. Deficits in visuospatial function were mainly related to postnatal exposures. These associations were stable after adjustment for confounders and exclusion of the children with the highest exposures to methylmercury and PCBs. Tests with good psychometric properties were more likely to show an association with mercury exposure. Greater sensitivity was also seen with tests administered by specialized academic staff rather than a trained technician. Despite highly significant effects on nervous system function, the deficits were subtle, and mercury exposure explained only a small part of the variation. Available evidence suggests that neurotoxicity may have severe implications on public health, but current methods are not amenable to application as sentinels of adverse health effects in environmental health surveillance.     

Consequences of gene targeting procedures for behavioural responses and morphological development of newborn mice

In this study the effects of gene targeting procedures on the early behaviour and morphological development of the resulting offspring have been investigated. Six groups of mice, each having undergone a specific aspect of the biotechnological procedure, (including electroporation, microinjection and/or embryo culture) and one control group, were compared. Development of behaviour, morphological characteristics and body weight of the progeny were tested daily from birth to weaning (0–3 weeks) for all groups. No significant differences in behaviour or morphological development were observed. However, the occurrence of increased (perinatal) pup mortality and increased body weight in the procedural groups, indicates that during the production of gene targeted mice, some of the normal physiological and/or developmental processes can be affected. Therefore, gene targeting procedures should always be accompanied by careful monitoring of health and welfare of the resulting offspring.     

Analysis of Profiles Based on Ordinal Classification Functions and Rank Tests

In this article a test for the comparison of K groups of independent profiles is suggested. It is based on rank tests, in which the criterion is obtained by using a suitably chosen ordinal classification function. This function represents a specific view on the profiles. The test, which is easy to use, can be regarded as a generalisation of other well known tests and can be applied within a variety of situations. The relationships to other procedures for the analysis of profiles are described. Some properties are discussed.     

The Structure of Ellipsoidal Distributions I. Canonical Analysis

This study is concerned with the structure of variables having ellipsoidal distributions. In Part I it is shown that many normal-theory results in canonical analysis are exact for all ellipsoidal distributions under a specified model for sampling. In Part II similar conclusions are drawn regarding the use of principal components. These findings suggest using normal-theory procedures in canonical and principal components analyses as approximate large-sample procedures for distributions attracted to ellipsoidal stable laws.     

Application of Multiple Test Procedures to the Combination of Multivariate and Univariate Tests with Varying Variable Sets

The positive ascertainment of location differences in a multivariate comparison of two or more groups gives rise to the question for the contribution of the single variables or of subsets of variables to the multivariate difference. In this paper two methods are proposed to accomplish the original multivariate test by tests in variable subsets or in single variables using a closed test procedure and Holm's procedure, respectively. Both control the multiple level of the whole procedure.     

On Some Nuisance Parameter Free Uniformly Most Powerful Tests

TAKEUCHI (1969) provides a uniformly most powerful (UMP) one side test for testing the location parameter of the two parameters exponential model when the scale parameter is unknown. The power of his similar size α test depends, however, on the unknown scale parameter. In this case and in more general situations when there exists a sufficient statistic for the nuisance parameter, the theory of generalized THOMPSON's distributions, more specifically, the Thompsonization of a test statistic, LAURENT (1959, 1972) provides a UMP test whose power does not depend on the nuisance parameter. Examples of application of the general nuisance parameter free test procedure include here the truncated exponential, the inverse Gaussian, and the geometric distributions.     

A More Powerful Simultaneous Test Procedure in Configural Frequency Analysis

In the Configural Frequency Analysis (CFA) of KRAUTH and LIENERT (1973 a, b), overfrequented (or underfrequented) cells in multivariate contingency tables are identified by simultaneous binomial tests. As an alternative, finite and asymptotic tests are proposed, which are derived from the (exact conditional) generalized hypergeometrical distribution of the cell frequencies. These tests allow for considerably more powerful decisions than do the conservative binomial tests.     

On the Assessment of the Performance of Multiple Test Procedures

Based on the concept of the multiple level of significance two criteria for assessing the performance of multiple tests are proposed: The simultaneous power is defined as the probability of rejecting all false null hypotheses. The probability of a correct decision is defined as the probability of correctly rejecting all false null hypotheses and accepting all true ones. Both criteria are discussed for nonstagewise and stagewise procedures in case of independent test statistics. For the example of 5 independently and normally distributed test statistics the values of the two criteria are calcutated under reasonably simple alternatives.