Robust Estimates of the Negative Binomial Model

We consider robust parametric procedures for univariate discrete distributions, focusing on the negative binomial model. The procedures are based on three steps: ?First, a very robust, but possibly inefficient, estimate of the model parameters is computed. ?Second, this initial model is used to identify outliers, which are then removed from the sample. ?Third, a corrected maximum likelihood estimator is computed with the remaining observations. The final estimate inherits the breakdown point (bdp) of the initial one and its efficiency can be significantly higher. Analogous procedures were proposed in [1], [2], [5] for the continuous case. A comparison of the asymptotic bias of various estimates under point contamination points out the minimum Neyman's chi-squared disparity estimate as a good choice for the initial step. Various minimum disparity estimators were explored by Lindsay [4], who showed that the minimum Neyman's chi-squared estimate has a 50% bdp under point contamination; in addition, it is asymptotically fully efficient at the model. However, the finite sample efficiency of this estimate under the uncontaminated negative binomial model is usually much lower than 100% and the bias can be strong. We show that its performance can then be greatly improved using the three step procedure outlined above. In addition, we compare the final estimate with the procedure described in

Computational toolbox towards evolutionary domain mapping of membrane proteins

Membrane proteins account for about 20% to 30% of all proteins encoded in a typical genome. They play central roles in multiple cellular processes mediating the interaction of the cell with its surrounding. Over 60% of all drug targets contain a membrane domain. The experimental difficulties of obtaining a crystal structural severely limits our ability or understanding of membrane protein function. Computational evolutionary studies of proteins are crucial for the prediction of 3D structures. In this project, we construct a tool able to quantify the evolutionary positive selective pressure on each residue of membrane proteins through maximum likelihood phylogeny reconstruction. The conservation plot combined with a structural homology model is also a potent tool to predict those residues that have essentials roles in the structure and function of a membrane protein and can be very useful in the design of validation experiments.

Heritability of ambulatory and office blood pressure in the Swiss population.

BACKGROUND: Blood pressure (BP) is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. We estimated the heritability of ambulatory and office BP in a Swiss population-based sample. METHODS: The Swiss Kidney Project on Genes in Hypertension is a population-based family study focusing on BP genetics. Office and ambulatory BP were measured in 1009 individuals from 271 nuclear families. Heritability was estimated for SBP, DBP, and pulse pressure using a maximum likelihood method implanted in the Statistical Analysis in Genetic Epidemiology software. RESULTS: The 518 women and 491 men included in this analysis had a mean (±SD) age of 48.3 (±17.4) and 47.3 (±17.7) years, and a mean BMI of 23.8 (±4.2) and 25.9 (±4.1) kg/m, respectively. Narrow-sense heritability estimates (±standard error) for ambulatory SBP, DBP, and pulse pressure were 0.37 ± 0.07, 0.26 ± 0.07, and 0.29 ± 0.07 for 24-h BP; 0.39 ± 0.07, 0.28 ± 0.07, and 0.27 ± 0.07 for day BP; and 0.25 ± 0.07, 0.20 ± 0.07, and 0.30 ± 0.07 for night BP, respectively (all P < 0.001). Heritability estimates for office SBP, DBP, and pulse pressure were 0.21 ± 0.08, 0.25 ± 0.08, and 0.18 ± 0.07 (all P < 0.01). CONCLUSIONS: We found significant heritability estimates for both ambulatory and office BP in this Swiss population-based study. Our findings justify the ongoing search for the genetic determinants of BP.

Pseudo-aneurismas: relato de dois casos e revisão da literatura

Pseudo-aneurismas são uma afecção arterial rara. Os autores destacam a raridade da ocorrência de pseudo-aneurisma da artéria carótida comum pós-traumático e a associação de pseudo-aneurisma com osteocondroma femoral. Enfatizam a importância dos métodos por imagem, em especial a angiotomografia, no diagnóstico de afecções vasculares, como na ocorrência de pseudo-aneurismas. Realizam, ainda, revisão bibliográfica pertinente ao assunto.

Divergent evolution and purifying selection of the flaA gene sequences in Aeromonas

BACKGROUND: The bacterial flagellum is the most important organelle of motility in bacteria and plays a key role in many bacterial lifestyles, including virulence. The flagellum also provides a paradigm of how hierarchical gene regulation, intricate protein-protein interactions and controlled protein secretion can result in the assembly of a complex multi-protein structure tightly orchestrated in time and space. As if to stress its importance, plants and animals produce receptors specifically dedicated to the recognition of flagella. Aside from motility, the flagellum also moonlights as an adhesion and has been adapted by humans as a tool for peptide display. Flagellar sequence variation constitutes a marker with widespread potential uses for studies of population genetics and phylogeny of bacterial species. RESULTS: We sequenced the complete flagellin gene (flaA) in 18 different species and subspecies of Aeromonas. Sequences ranged in size from 870 (A. allosaccharophila) to 921 nucleotides (A. popoffii). The multiple alignment displayed 924 sites, 66 of which presented alignment gaps. The phylogenetic tree revealed the existence of two groups of species exhibiting different FlaA flagellins (FlaA1 and FlaA2). Maximum likelihood models of codon substitution were used to analyze flaA sequences. Likelihood ratio tests suggested a low variation in selective pressure among lineages, with an omega ratio of less than 1 indicating the presence of purifying selection in almost all cases. Only one site under potential diversifying selection was identified (isoleucine in position 179). However, 17 amino acid positions were inferred as sites that are likely to be under positive selection using the branch-site model. Ancestral reconstruction revealed that these 17 amino acids were among the amino acid changes detected in the ancestral sequence. CONCLUSION: The models applied to our set of sequences allowed us to determine the possible evolutionary pathway followed by the flaA gene in Aeromonas, suggesting that this gene have probably been evolving independently in the two groups of Aeromonas species since the divergence of a distant common ancestor after one or several episodes of positive selection. REVIEWERS: This article was reviewed by Alexey Kondrashov, John Logsdon and Olivier Tenaillon (nominated by Laurence D Hurst).

Pseudo-Próspero de Aquitania, Sobre la providencia de Dios. Introducción, texto latino revisado, traducción y comentario de Raúl Villegas Marín, Publicacions i edicions de la Universitat de Barcelona, Barcelona 2010, 346 pp. ISBN 9788447534869

El primer tercio del siglo V representó un momento muy convulso en la historia del Imperio Romano. Algunas zonas, como la Galia, se vieron inmersas en una crisis provocada principalmente por las devastaciones que poblaciones bárbaras estaban llevando a cabo, desde inicios de la centuria, en casi todo su territorio. El foedus pactado por el Imperio con los visigodos, por el cual éstos se establecían en Aquitania (418), lejos de representar una solución no hizo sino aumentar los problemas de convivencia entre galorromanos y germanos. El pesimismo cundió entre la población autóctona: la teología eusebiana que presentaba al Dios cristiano como garante de los bienes materiales a través de su culto ―siguiendo la tradicional ideología del do ut des― había fallado, y muchas conciencias cristianas se hundieron en la angustia al preg

The pseudo-high-risk prevention strategy

Key Messages: A fundamental failure of high-risk prevention strategies is their inability to prevent disease in the large part of the population at a relatively small average risk and from which most cases of diseases originate. The development of individual predictive medicine and the widening of high-risk categories for numerous (chronic) conditions lead to the application of pseudo-high-risk prevention strategies. Widening the criteria justifying individual preventive interventions and the related pseudo-high-risk strategies lead to treating, individually, ever healthier and larger strata of the population. The pseudo-high-risk prevention strategies raise similar problems compared with high-risk strategies, however on a larger scale and without any of the benefit of population-based strategies. Some 30 years ago, the strengths and weaknesses of population-based and high-risk prevention strategies were brilliantly delineated by Geoffrey Rose in several seminal publications (Table 1).1,2 His work had major implications not only for epidemiology and public health but also for clinical medicine. In particular, Rose demonstrated the fundamental failure of high-risk prevention strategies, that is, by missing a large number of preventable cases.

Combining conservative and variable markers to inferthe evolutionary history of Prunus subgen. Amygdalus s.l.under domestication

The genus Prunus L. is large and economically important. However, phylogenetic relationships within Prunus at low taxonomic level, particularly in the subgenus Amygdalus L. s.l., remain poorly investigated. This paper attempts to document the evolutionary history of Amygdalus s.l. and establishes a temporal framework, by assembling molecular data from conservative and variable molecular markers. The nuclear s6pdh gene in combination with the plastid trnSG spacer are analyzed with bayesian and maximum likelihood methods. Since previous phylogenetic analysis with these markers lacked resolution, we additionally analyzed 13 nuclear SSR loci with the δµ2 distance, followed by an unweighted pair group method using arithmetic averages algorithm. Our phylogenetic analysis with both sequence and SSR loci confirms the split between sections Amygdalus and Persica, comprising almonds and peaches, respectively. This result is in agreement with biogeographic data showing that each of the two sections is naturally distributed on each side of the Central Asian Massif chain. Using coalescent based estimations, divergence times between the two sections strongly varied when considering sequence data only or combined with SSR. The sequence-only based estimate (5 million years ago) was congruent with the Central Asian Massif orogeny and subsequent climate change. Given the low level of differentiation within the two sections using both marker types, the utility of combining microsatellites and data sequences to address phylogenetic relationships at low taxonomic level within Amygdalus is discussed. The recent evolutionary histories of almond and peach are discussed in view of the domestication processes that arose in these two phenotypically-diverging gene pools: almonds and peaches were domesticated from the Amygdalus s.s. and Persica sections, respectively. Such economically important crops may serve as good model to study divergent domestication process in close genetic pool.

Dismissal of the illusion of uncertainty in the assessment of a likelihood ratio

The use of the Bayes factor (BF) or likelihood ratio as a metric to assess the probative value of forensic traces is largely supported by operational standards and recommendations in different forensic disciplines. However, the progress towards more widespread consensus about foundational principles is still fragile as it raises new problems about which views differ. It is not uncommon e.g. to encounter scientists who feel the need to compute the probability distribution of a given expression of evidential value (i.e. a BF), or to place intervals or significance probabilities on such a quantity. The article here presents arguments to show that such views involve a misconception of principles and abuse of language. The conclusion of the discussion is that, in a given case at hand, forensic scientists ought to offer to a court of justice a given single value for the BF, rather than an expression based on a distribution over a range of values.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.

A Computer program for estimating population size by the removal method

A BASIC computer program (REMOVAL) was developed to compute in a VAXNMS environment all the calculations of the removal method for population size estimation (catch-effort method for closed populations with constant sampling effort). The program follows the maximum likelihood methodology,checks the failure conditions, applies the appropriate formula, and displays the estimates of population size and catchability, with their standard deviations and coefficients of variation, and two goodness-of-fit statistics with their significance levels. Data of removal experiments for the cyprinodontid fish Aphanius iberus in the Alt Emporda wetlands are used to exemplify the use of the program