Non-random autosome segregation: a stepping stone for the evolution of sex chromosome complexes?

A new study in Caenorhabditis elegans shows that homologous autosomes segregate non-randomly with the sex chromosome in the heterogametic sex. Segregation occurs according to size, small autosomes segregating with, and large autosomes segregating away from the X-chromosome. Such sex-biased transmission of autosomes could facilitate the spread of sexually antagonistic alleles whose effects favor the fitness of one sex at the expense of the other. This may provide a first step toward the evolution of new sex determination systems.

Can Valproic Acid be an Inducer of Clozapine Metabolism?

Introduction: Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that (i) VPA is a net inducer of clozapine metabolism, and (ii) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. Methods: After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. Results: VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14-39%) after controlling for confounding variables including smoking (35% lower, 28-56%). Discussion: Prospective studies are needed to definitively establish that VPA may (i) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and (ii) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism.

Stability and robustness of blood variables in an antidoping context.

Introduction:  With the setting up of the newly Athlete's Biological Passport antidoping programme, novel guidelines have been introduced to guarantee results beyond reproach. We investigated in this context, the effect of storage time on the variables commonly measured for the haematological passport. We also wanted to assess for these variables, the within and between analyzer variations. Methods:  Blood samples were obtained from top level male professional cyclists (27 samples for the first part of the study and 102 for the second part) taking part to major stage races. After collection, they were transported under refrigerated conditions (2 °C < T < 12 °C), delivered to the antidoping laboratory, analysed and then stored at approximately 4 °C to conduct analysis at different time points up to 72 h after delivery. A mixed-model procedure was used to determine the stability of the different variables. Results:  As expected haemoglobin concentration was not affected by storage and showed stability for at least 72 h. Under the conditions of our investigation, the reticulocytes percentage showed a much better stability than previous published data (> 48 h) and the technical comparison of the haematology analyzer demonstrated excellent results. Conclusion:  In conclusion, our data clearly demonstrate that as long as the World Anti-Doping Agency's guidelines are followed rigorously, all blood results reach the quality level required in the antidoping context.

Stochastic differential equations with random coefficients

In this paper we establish the existence and uniqueness of a solution for different types of stochastic differential equation with random initial conditions and random coefficients. The stochastic integral is interpreted as a generalized Stratonovich integral, and the techniques used to derive these results are mainly based on the path properties of the Brownian motion, and the definition of the Stratonovich integral.

Linear random knots and their scaling behavior

We present here a nonbiased probabilistic method that allows us to consistently analyze knottedness of linear random walks with up to several hundred noncorrelated steps. The method consists of analyzing the spectrum of knots formed by multiple closures of the same open walk through random points on a sphere enclosing the walk. Knottedness of individual "frozen" configurations of linear chains is therefore defined by a characteristic spectrum of realizable knots. We show that in the great majority of cases this method clearly defines the dominant knot type of a walk, i.e., the strongest component of the spectrum. In such cases, direct end-to-end closure creates a knot that usually coincides with the knot type that dominates the random closure spectrum. Interestingly, in a very small proportion of linear random walks, the knot type is not clearly defined. Such walks can be considered as residing in a border zone of the configuration space of two or more knot types. We also characterize the scaling behavior of linear random knots.

Random assignment of intervention points in two phase single-case designs: data-division-specific distributions

The present study explores the statistical properties of a randomization test based on the random assignment of the intervention point in a two-phase (AB) single-case design. The focus is on randomization distributions constructed with the values of the test statistic for all possible random assignments and used to obtain p-values. The shape of those distributions is investigated for each specific data division defined by the moment in which the intervention is introduced. Another aim of the study consisted in testing the detection of inexistent effects (i.e., production of false alarms) in autocorrelated data series, in which the assumption of exchangeability between observations may be untenable. In this way, it was possible to compare nominal and empirical Type I error rates in order to obtain evidence on the statistical validity of the randomization test for each individual data division. The results suggest that when either of the two phases has considerably less measurement times, Type I errors may be too probable and, hence, the decision making process to be carried out by applied researchers may be jeopardized.

Las relaciones actitud-conducta y'otras variables' a partir de la teoría de Fishbein y Ajzena y del modelo LISREL: Estudio empírico

A través de la investigación presentada en este articulo se ha pretendido operacionalizar la parte predictiva de la Teoria de Acción Razonada, propuesta por Fishbein y Ajzen. Para ello, se ha utilizado la reciente metodologia de 10s modelos de ecuaciones estructurales lineales con variables latentes desarrollados por Joreskog y Sorbom, entre otros. Como dominio se ha delimitado el consumo de tabaco en distintas situaciones sociales. Después de estimar y valorar el modelo predictivo especificado desde la Teoria de Fishbein y Ajzen, se estimo y valoro el modelo generalizado propuesto por Bentler y Speckart y se asumió como mas coherente este modelo generalizado. En el trabajo también se plantean una serie de observaciones para optimizar, sobre todo, la parte metodológica de recogida de datos asociados a estos modelos y se presenta una propuesta para operacionalizar todo el sistema teórico de predicción y explicación de las conductas desde la Teoria de Fishbein y Ajzen.

Retaining principal components for discrete variables

The present study discusses retention criteria for principal components analysis (PCA) applied to Likert scale items typical in psychological questionnaires. The main aim is to recommend applied researchers to restrain from relying only on the eigenvalue-than-one criterion; alternative procedures are suggested for adjusting for sampling error. An additional objective is to add evidence on the consequences of applying this rule when PCA is used with discrete variables. The experimental conditions were studied by means of Monte Carlo sampling including several sample sizes, different number of variables and answer alternatives, and four non-normal distributions. The results suggest that even when all the items and thus the underlying dimensions are independent, eigenvalues greater than one are frequent and they can explain up to 80% of the variance in data, meeting the empirical criterion. The consequences of using Kaiser"s rule are illustrated with a clinical psychology example. The size of the eigenvalues resulted to be a function of the sample size and the number of variables, which is also the case for parallel analysis as previous research shows. To enhance the application of alternative criteria, an R package was developed for deciding the number of principal components to retain by means of confidence intervals constructed about the eigenvalues corresponding to lack of relationship between discrete variables.

School burnout in adolescents : Differences in background variables and exploration of school-related stress at the end of compulsory schooling

The aim of this study is to contribute to a better understanding of the risk factors associated with school burnout, which has recently been described as a syndrome of emotional exhaustion due to school demands, cynical and detached attitude towards school and feelings of inadequacy as a student (Salmela-Aro, Kiuru, Pietikainen & Jokela, 2008a). The research focuses on students in the last years of compulsory schooling, period in which burnout has not received much attention yet. A total of 342 adolescents (Mean age = 14.84) were asked to complete questionnaires about school burnout, school-related stress and background variables. The results showed differences in school burnout by gender, grade level and school track, with girls, last grade of compulsory school and high-track classes, showing the highest scores. No difference was observed with respect to grade retention. Several types of school stress were identified, with stress type Success related to pressures to succeed and concerns about the academic future being the highest. Finally, stress and burnout were strongly and positively correlated, and the type of stress Success was the best predictor of overall Burnout, Exhaustion and Inadequacy dimension scores. The results are discussed in relation to their theoretical relevance and implications for the prevention of school burnout in adolescents.

Family burden related to clinical and functional variables of people with intellectual disability with and without a mental disorder

Few studies have been found that to assess the factors that explain higher levels of familyburden in adults with intellectualdisability (ID) and intellectualdisability and mental disorders (ID-MD). The aims of this study were to assess familyburden in people with ID and ID-MD and to determine which sociodemographic, clinical and functionaldisabilityvariables account for familyburden. The sample is composed of pairs of 203 participants with disability and their caregivers, of which 33.5% are caregivers of people with ID and 66.5% of ID-MD. Assessments were performed using scales of clinical and functionaldisability as the following instruments: Weschler Adult Intelligence Scale-III (WAIS-III), Inventory for Client and Agency Planning (ICAP), Psychiatric Assessment Schedule for Adults with Development Disability (PAS-ADD checklist), Disability Assessment Schedule of the World Health Organization (WHO-DAS-II) and familyburden (Subjective and Objective FamilyBurden Inventory - SOFBI/ECFOS-II). People with ID-MD presented higher levels of functionaldisability than those with ID only. Higher levels of familyburden were related to higher functionaldisability in all the areas (p < 0.006-0.001), lower intelligence quotient (p < 0.001), diagnosis of ID-MD (p < 0.001) and presence of organic, affective, psychotic and behavioral disorders (p < 0.001). Stepwise multiple regression showed that behavioral problems, affective and psychotic disorder, disability in participation in society, disability in personal care and presence of ID-MD explained more than 61% of the variance in familyburden. An integrated approach using effective multidimensional interventions is essential for both people with ID and ID-MD and their caregivers in order to reduce familyburden.

Predictive analysis and mapping of indoor radon concentrations in Switzerland

It is estimated that around 230 people die each year due to radon (222Rn) exposure in Switzerland. 222Rn occurs mainly in closed environments like buildings and originates primarily from the subjacent ground. Therefore it depends strongly on geology and shows substantial regional variations. Correct identification of these regional variations would lead to substantial reduction of 222Rn exposure of the population based on appropriate construction of new and mitigation of already existing buildings. Prediction of indoor 222Rn concentrations (IRC) and identification of 222Rn prone areas is however difficult since IRC depend on a variety of different variables like building characteristics, meteorology, geology and anthropogenic factors. The present work aims at the development of predictive models and the understanding of IRC in Switzerland, taking into account a maximum of information in order to minimize the prediction uncertainty. The predictive maps will be used as a decision-support tool for 222Rn risk management. The construction of these models is based on different data-driven statistical methods, in combination with geographical information systems (GIS). In a first phase we performed univariate analysis of IRC for different variables, namely the detector type, building category, foundation, year of construction, the average outdoor temperature during measurement, altitude and lithology. All variables showed significant associations to IRC. Buildings constructed after 1900 showed significantly lower IRC compared to earlier constructions. We observed a further drop of IRC after 1970. In addition to that, we found an association of IRC with altitude. With regard to lithology, we observed the lowest IRC in sedimentary rocks (excluding carbonates) and sediments and the highest IRC in the Jura carbonates and igneous rock. The IRC data was systematically analyzed for potential bias due to spatially unbalanced sampling of measurements. In order to facilitate the modeling and the interpretation of the influence of geology on IRC, we developed an algorithm based on k-medoids clustering which permits to define coherent geological classes in terms of IRC. We performed a soil gas 222Rn concentration (SRC) measurement campaign in order to determine the predictive power of SRC with respect to IRC. We found that the use of SRC is limited for IRC prediction. The second part of the project was dedicated to predictive mapping of IRC using models which take into account the multidimensionality of the process of 222Rn entry into buildings. We used kernel regression and ensemble regression tree for this purpose. We could explain up to 33% of the variance of the log transformed IRC all over Switzerland. This is a good performance compared to former attempts of IRC modeling in Switzerland. As predictor variables we considered geographical coordinates, altitude, outdoor temperature, building type, foundation, year of construction and detector type. Ensemble regression trees like random forests allow to determine the role of each IRC predictor in a multidimensional setting. We found spatial information like geology, altitude and coordinates to have stronger influences on IRC than building related variables like foundation type, building type and year of construction. Based on kernel estimation we developed an approach to determine the local probability of IRC to exceed 300 Bq/m3. In addition to that we developed a confidence index in order to provide an estimate of uncertainty of the map. All methods allow an easy creation of tailor-made maps for different building characteristics. Our work is an essential step towards a 222Rn risk assessment which accounts at the same time for different architectural situations as well as geological and geographical conditions. For the communication of 222Rn hazard to the population we recommend to make use of the probability map based on kernel estimation. The communication of 222Rn hazard could for example be implemented via a web interface where the users specify the characteristics and coordinates of their home in order to obtain the probability to be above a given IRC with a corresponding index of confidence. Taking into account the health effects of 222Rn, our results have the potential to substantially improve the estimation of the effective dose from 222Rn delivered to the Swiss population.