KCM, a general framework for codon-based model of evolution

With the advancement of high-throughput sequencing and dramatic increase of available genetic data, statistical modeling has become an essential part in the field of molecular evolution. Statistical modeling results in many interesting discoveries in the field, from detection of highly conserved or diverse regions in a genome to phylogenetic inference of species evolutionary history Among different types of genome sequences, protein coding regions are particularly interesting due to their impact on proteins. The building blocks of proteins, i.e. amino acids, are coded by triples of nucleotides, known as codons. Accordingly, studying the evolution of codons leads to fundamental understanding of how proteins function and evolve. The current codon models can be classified into three principal groups: mechanistic codon models, empirical codon models and hybrid ones. The mechanistic models grasp particular attention due to clarity of their underlying biological assumptions and parameters. However, they suffer from simplified assumptions that are required to overcome the burden of computational complexity. The main assumptions applied to the current mechanistic codon models are (a) double and triple substitutions of nucleotides within codons are negligible, (b) there is no mutation variation among nucleotides of a single codon and (c) assuming HKY nucleotide model is sufficient to capture essence of transition- transversion rates at nucleotide level. In this thesis, I develop a framework of mechanistic codon models, named KCM-based model family framework, based on holding or relaxing the mentioned assumptions. Accordingly, eight different models are proposed from eight combinations of holding or relaxing the assumptions from the simplest one that holds all the assumptions to the most general one that relaxes all of them. The models derived from the proposed framework allow me to investigate the biological plausibility of the three simplified assumptions on real data sets as well as finding the best model that is aligned with the underlying characteristics of the data sets. -- Avec l'avancement de séquençage à haut débit et l'augmentation dramatique des données géné¬tiques disponibles, la modélisation statistique est devenue un élément essentiel dans le domaine dé l'évolution moléculaire. Les résultats de la modélisation statistique dans de nombreuses découvertes intéressantes dans le domaine de la détection, de régions hautement conservées ou diverses dans un génome de l'inférence phylogénétique des espèces histoire évolutive. Parmi les différents types de séquences du génome, les régions codantes de protéines sont particulièrement intéressants en raison de leur impact sur les protéines. Les blocs de construction des protéines, à savoir les acides aminés, sont codés par des triplets de nucléotides, appelés codons. Par conséquent, l'étude de l'évolution des codons mène à la compréhension fondamentale de la façon dont les protéines fonctionnent et évoluent. Les modèles de codons actuels peuvent être classés en trois groupes principaux : les modèles de codons mécanistes, les modèles de codons empiriques et les hybrides. Les modèles mécanistes saisir une attention particulière en raison de la clarté de leurs hypothèses et les paramètres biologiques sous-jacents. Cependant, ils souffrent d'hypothèses simplificatrices qui permettent de surmonter le fardeau de la complexité des calculs. Les principales hypothèses retenues pour les modèles actuels de codons mécanistes sont : a) substitutions doubles et triples de nucleotides dans les codons sont négligeables, b) il n'y a pas de variation de la mutation chez les nucléotides d'un codon unique, et c) en supposant modèle nucléotidique HKY est suffisant pour capturer l'essence de taux de transition transversion au niveau nucléotidique. Dans cette thèse, je poursuis deux objectifs principaux. Le premier objectif est de développer un cadre de modèles de codons mécanistes, nommé cadre KCM-based model family, sur la base de la détention ou de l'assouplissement des hypothèses mentionnées. En conséquence, huit modèles différents sont proposés à partir de huit combinaisons de la détention ou l'assouplissement des hypothèses de la plus simple qui détient toutes les hypothèses à la plus générale qui détend tous. Les modèles dérivés du cadre proposé nous permettent d'enquêter sur la plausibilité biologique des trois hypothèses simplificatrices sur des données réelles ainsi que de trouver le meilleur modèle qui est aligné avec les caractéristiques sous-jacentes des jeux de données. Nos expériences montrent que, dans aucun des jeux de données réelles, tenant les trois hypothèses mentionnées est réaliste. Cela signifie en utilisant des modèles simples qui détiennent ces hypothèses peuvent être trompeuses et les résultats de l'estimation inexacte des paramètres. Le deuxième objectif est de développer un modèle mécaniste de codon généralisée qui détend les trois hypothèses simplificatrices, tandis que d'informatique efficace, en utilisant une opération de matrice appelée produit de Kronecker. Nos expériences montrent que sur un jeux de données choisis au hasard, le modèle proposé de codon mécaniste généralisée surpasse autre modèle de codon par rapport à AICc métrique dans environ la moitié des ensembles de données. En outre, je montre à travers plusieurs expériences que le modèle général proposé est biologiquement plausible.

The Lithium, Boron and Beryllium content of serpentinized peridotites from ODP Leg 209 (Sites 1272A and 1274A): Implications for lithium and boron budgets of oceanic lithosphere

Despite the key importance of altered oceanic mantle as a repository and carrier of light elements (B, Li, and Be) to depth, its inventory of these elements has hardly been explored and quantified. In order to constrain the systematics and budget of these elements we have studied samples of highly serpentinized (>50%) spinel harzburgite drilled at the Mid-Atlantic Ridge (Fifteen-Twenty Fracture zone, ODP Leg 209, Sites 1272A and 1274A). In-situ analysis by secondary ion mass spectrometry reveals that the B, Li and Be contents of mantle minerals (olivine, orthopyroxene, and clinopyroxene) remain unchanged during serpentinization. B and Li abundances largely correspond to those of unaltered mantle minerals whereas Be is close to the detection limit. The Li contents of clinopyroxene are slightly higher (0.44-2.8 mu g g(-1)) compared to unaltered mantle clinopyroxene, and olivine and clinopyroxene show an inverse Li partitioning compared to literature data. These findings along with textural observations and major element composition obtained from microprobe analysis suggest reaction of the peridotites with a mafic silicate melt before serpentinization. Serpentine minerals are enriched in B (most values between 10 and 100 mu g g(-1)), depleted in Li (most values below I mu g g(-1)) compared to the primary phases, with considerable variation within and between samples. Be is at the detection limit. Analysis of whole rock samples by prompt gamma activation shows that serpentinization tends to increase B (10.4-65.0 mu g g(-1)), H2O and Cl contents and to lower Li contents (0.07-3.37 mu g g(-1)) of peridotites, implying that-contrary to alteration of oceanic crust-B is fractionated from Li and that the B and Li inventory should depend essentially on rock-water ratios. Based on our results and on literature data, we calculate the inventory of B and Li contained in the oceanic lithosphere, and its partitioning between crust and mantle as a function of plate characteristics. We model four cases, an ODP Leg 209-type lithosphere with almost no igneous crust, and a Semail-type lithosphere with a thick igneous crust, both at I and 75 Ma, respectively. The results show that the Li contents of the oceanic lithosphere are highly variable (17-307 kg in a column of I m x I m x thickness of the lithosphere (kg/col)). They are controlled by the primary mantle phases and by altered crust, whereas the B contents (25-904 kg/col) depend entirely on serpentinization. In all cases, large quantities of B reside in the uppermost part of the plate and could hence be easily liberated during slab dehydration. The most prominent input of Li into subduction zones is to be expected from Semail-type lithosphere because most of the Li is stored at shallow levels in the plate. Subducting an ODP Leg 209-type lithosphere would mean only very little Li contribution from the slab. Serpentinized mantle thus plays an important role in B recycling in subduction zones, but it is of lesser importance for Li. (C) 2008 Elsevier Ltd. All rights reserved.

Looking for orders of magnitude : five essays in trade and the environment and economic geography

General Summary Although the chapters of this thesis address a variety of issues, the principal aim is common: test economic ideas in an international economic context. The intention has been to supply empirical findings using the largest suitable data sets and making use of the most appropriate empirical techniques. This thesis can roughly be divided into two parts: the first one, corresponding to the first two chapters, investigates the link between trade and the environment, the second one, the last three chapters, is related to economic geography issues. Environmental problems are omnipresent in the daily press nowadays and one of the arguments put forward is that globalisation causes severe environmental problems through the reallocation of investments and production to countries with less stringent environmental regulations. A measure of the amplitude of this undesirable effect is provided in the first part. The third and the fourth chapters explore the productivity effects of agglomeration. The computed spillover effects between different sectors indicate how cluster-formation might be productivity enhancing. The last chapter is not about how to better understand the world but how to measure it and it was just a great pleasure to work on it. "The Economist" writes every week about the impressive population and economic growth observed in China and India, and everybody agrees that the world's center of gravity has shifted. But by how much and how fast did it shift? An answer is given in the last part, which proposes a global measure for the location of world production and allows to visualize our results in Google Earth. A short summary of each of the five chapters is provided below. The first chapter, entitled "Unraveling the World-Wide Pollution-Haven Effect" investigates the relative strength of the pollution haven effect (PH, comparative advantage in dirty products due to differences in environmental regulation) and the factor endowment effect (FE, comparative advantage in dirty, capital intensive products due to differences in endowments). We compute the pollution content of imports using the IPPS coefficients (for three pollutants, namely biological oxygen demand, sulphur dioxide and toxic pollution intensity for all manufacturing sectors) provided by the World Bank and use a gravity-type framework to isolate the two above mentioned effects. Our study covers 48 countries that can be classified into 29 Southern and 19 Northern countries and uses the lead content of gasoline as proxy for environmental stringency. For North-South trade we find significant PH and FE effects going in the expected, opposite directions and being of similar magnitude. However, when looking at world trade, the effects become very small because of the high North-North trade share, where we have no a priori expectations about the signs of these effects. Therefore popular fears about the trade effects of differences in environmental regulations might by exaggerated. The second chapter is entitled "Is trade bad for the Environment? Decomposing worldwide SO2 emissions, 1990-2000". First we construct a novel and large database containing reasonable estimates of SO2 emission intensities per unit labor that vary across countries, periods and manufacturing sectors. Then we use these original data (covering 31 developed and 31 developing countries) to decompose the worldwide SO2 emissions into the three well known dynamic effects (scale, technique and composition effect). We find that the positive scale (+9,5%) and the negative technique (-12.5%) effect are the main driving forces of emission changes. Composition effects between countries and sectors are smaller, both negative and of similar magnitude (-3.5% each). Given that trade matters via the composition effects this means that trade reduces total emissions. We next construct, in a first experiment, a hypothetical world where no trade happens, i.e. each country produces its imports at home and does no longer produce its exports. The difference between the actual and this no-trade world allows us (under the omission of price effects) to compute a static first-order trade effect. The latter now increases total world emissions because it allows, on average, dirty countries to specialize in dirty products. However, this effect is smaller (3.5%) in 2000 than in 1990 (10%), in line with the negative dynamic composition effect identified in the previous exercise. We then propose a second experiment, comparing effective emissions with the maximum or minimum possible level of SO2 emissions. These hypothetical levels of emissions are obtained by reallocating labour accordingly across sectors within each country (under the country-employment and the world industry-production constraints). Using linear programming techniques, we show that emissions are reduced by 90% with respect to the worst case, but that they could still be reduced further by another 80% if emissions were to be minimized. The findings from this chapter go together with those from chapter one in the sense that trade-induced composition effect do not seem to be the main source of pollution, at least in the recent past. Going now to the economic geography part of this thesis, the third chapter, entitled "A Dynamic Model with Sectoral Agglomeration Effects" consists of a short note that derives the theoretical model estimated in the fourth chapter. The derivation is directly based on the multi-regional framework by Ciccone (2002) but extends it in order to include sectoral disaggregation and a temporal dimension. This allows us formally to write present productivity as a function of past productivity and other contemporaneous and past control variables. The fourth chapter entitled "Sectoral Agglomeration Effects in a Panel of European Regions" takes the final equation derived in chapter three to the data. We investigate the empirical link between density and labour productivity based on regional data (245 NUTS-2 regions over the period 1980-2003). Using dynamic panel techniques allows us to control for the possible endogeneity of density and for region specific effects. We find a positive long run elasticity of density with respect to labour productivity of about 13%. When using data at the sectoral level it seems that positive cross-sector and negative own-sector externalities are present in manufacturing while financial services display strong positive own-sector effects. The fifth and last chapter entitled "Is the World's Economic Center of Gravity Already in Asia?" computes the world economic, demographic and geographic center of gravity for 1975-2004 and compares them. Based on data for the largest cities in the world and using the physical concept of center of mass, we find that the world's economic center of gravity is still located in Europe, even though there is a clear shift towards Asia. To sum up, this thesis makes three main contributions. First, it provides new estimates of orders of magnitudes for the role of trade in the globalisation and environment debate. Second, it computes reliable and disaggregated elasticities for the effect of density on labour productivity in European regions. Third, it allows us, in a geometrically rigorous way, to track the path of the world's economic center of gravity.

Efficiency of nitrogen fertilizer applied at corn sowing in contrasting growing seasons in Paraguay

In order to select soil management practices that increase the nitrogen-use efficiency (NUE) in agro-ecosystems, the different indices of agronomic fertilizer efficiency must be evaluated under varied weather conditions. This study assessed the NUE indices in no-till corn in southern Paraguay. Nitrogen fertilizer rates from 0 to 180 kg ha-1 were applied in a single application at corn sowing and the crop response investigated in two growing seasons (2010 and 2011). The experimental design was a randomized block with three replications. Based on the data of grain yield, dry matter, and N uptake, the following fertilizer indices were assessed: agronomic N-use efficiency (ANE), apparent N recovery efficiency (NRE), N physiological efficiency (NPE), partial factor productivity (PFP), and partial nutrient balance (PNB). The weather conditions varied largely during the experimental period; the rainfall distribution was favorable for crop growth in the first season and unfavorable in the second. The PFP and ANE indices, as expected, decreased with increasing N fertilizer rates. A general analysis of the N fertilizer indices in the first season showed that the maximum rate (180 kg ha-1) obtained the highest corn yield and also optimized the efficiency of NPE, NRE and ANE. In the second season, under water stress, the most efficient N fertilizer rate (60 kg ha-1) was three times lower than in the first season, indicating a strong influence of weather conditions on NUE. Considering that weather instability is typical for southern Paraguay, anticipated full N fertilization at corn sowing is not recommended due the temporal variability of the optimum N fertilizer rate needed to achieve high ANE.

Evolution of mRNA expression levels of autosomal and sex-linked genes in amniotes

In addition to differences in protein-coding gene sequences, changes in expression resulting from mutations in regulatory sequences have long been hypothesized to be responsible for phenotypic differences between species. However, unlike comparison of genome sequences, few studies, generally restricted to pairwise comparisons of closely related mammalian species, have assessed between-species differences at the transcriptome level. They reported that gene expression evolves at different rates in various organs and in a pattern that is overall consistent with neutral models of evolution. In the first part of my thesis, I investigated the evolution of gene expression in therian mammals (i.e.7 placental and marsupials), based on microarray data from human, mouse and the gray short-tailed opossum (Monodelphis domestica). In addition to autosomal genes, a special focus was given to the evolution of X-linked genes. The therian X chromosome was recently shown to be younger than previously thought and to harbor a specific gene content (e.g., genes involved in brain or reproductive functions) that is thought to have been shaped by specific sex-related evolutionary forces. Sex chromosomes derive from ordinary autosomes and their differentiation led to the degeneration of the Y chromosome (in mammals) or W chromosome (in birds). Consequently, X- or Z-linked genes differ in gene dose between males and females such that the heterogametic sex has half the X/Z gene dose compared to the ancestral state. To cope with this dosage imbalance, mammals have been reported to have evolved mechanisms of dosage compensation.¦In the first project, I could first show that transcriptomes evolve at different rates in different organs. Out of the five tissues I investigated, the testis is the most rapidly evolving organ at the gene expression level while the brain has the most conserved transcriptome. Second, my analyses revealed that mammalian gene expression evolution is compatible with a neutral model, where the rates of change in gene expression levels is linked to the efficiency of purifying selection in a given lineage, which, in turn, is determined by the long-term effective population size in that lineage. Thus, the rate of DNA sequence evolution, which could be expected to determine the rate of regulatory sequence change, does not seem to be a major determinant of the rate of gene expression evolution. Thus, most gene expression changes seem to be (slightly) deleterious. Finally, X-linked genes seem to have experienced elevated rates of gene expression change during the early stage of X evolution. To further investigate the evolution of mammalian gene expression, we generated an extensive RNA-Seq gene expression dataset for nine mammalian species and a bird. The analyses of this dataset confirmed the patterns previously observed with microarrays and helped to significantly deepen our view on gene expression evolution.¦In a specific project based on these data, I sought to assess in detail patterns of evolution of dosage compensation in amniotes. My analyses revealed the absence of male to female dosage compensation in monotremes and its presence in marsupials and, in addition, confirmed patterns previously described for placental mammals and birds. I then assessed the global level of expression of X/Z chromosomes and contrasted this with its ancestral gene expression levels estimated from orthologous autosomal genes in species with non-homologous sex chromosomes. This analysis revealed a lack of up-regulation for placental mammals, the level of expression of X-linked genes being proportional to gene dose. Interestingly, the ancestral gene expression level was at least partially restored in marsupials as well as in the heterogametic sex of monotremes and birds. Finally, I investigated alternative mechanisms of dosage compensation and found that gene duplication did not seem to be a widespread mechanism to restore the ancestral gene dose. However, I could show that placental mammals have preferentially down-regulated autosomal genes interacting with X-linked genes which underwent gene expression decrease, and thus identified a novel alternative mechanism of dosage compensation.

Comparing the artificial neural network with parcial least squares for prediction of soil organic carbon and pH at different moisture content levels using visible and near-infrared spectroscopy

Visible and near infrared (vis-NIR) spectroscopy is widely used to detect soil properties. The objective of this study is to evaluate the combined effect of moisture content (MC) and the modeling algorithm on prediction of soil organic carbon (SOC) and pH. Partial least squares (PLS) and the Artificial neural network (ANN) for modeling of SOC and pH at different MC levels were compared in terms of efficiency in prediction of regression. A total of 270 soil samples were used. Before spectral measurement, dry soil samples were weighed to determine the amount of water to be added by weight to achieve the specified gravimetric MC levels of 5, 10, 15, 20, and 25 %. A fiber-optic vis-NIR spectrophotometer (350-2500 nm) was used to measure spectra of soil samples in the diffuse reflectance mode. Spectra preprocessing and PLS regression were carried using Unscrambler® software. Statistica® software was used for ANN modeling. The best prediction result for SOC was obtained using the ANN (RMSEP = 0.82 % and RPD = 4.23) for soil samples with 25 % MC. The best prediction results for pH were obtained with PLS for dry soil samples (RMSEP = 0.65 % and RPD = 1.68) and soil samples with 10 % MC (RMSEP = 0.61 % and RPD = 1.71). Whereas the ANN showed better performance for SOC prediction at all MC levels, PLS showed better predictive accuracy of pH at all MC levels except for 25 % MC. Therefore, based on the data set used in the current study, the ANN is recommended for the analyses of SOC at all MC levels, whereas PLS is recommended for the analysis of pH at MC levels below 20 %.

Multidimensionnalité des violences envers les femmes. La Suisse en regard des États-Unis: pertinence et validité d'une comparaison

Summary : International comparisons in the area of victimization, particularly in the field of violence against women, are fraught with methodological problems that previous research has not systematically addressed, and whose answer does not seem to be agreed up~n. For obvious logistic and financial reasons, international studies on violence against women (i.e. studies that administer the same instrument in different countries). are seldom; therefore, researchers are bound to resort to secondary comparisons. Many studies simply juxtapose their results to the ones of previous wòrk or to findings obtained in different contexts, in order to offer an allegedly comparative perspective to their conclusions. If, most of the time, researchers indicate the methodological limitations of a direct comparison, it is not rare that these do not result in concrete methodological controls. Yet, many studies have shown the influence of surveys methodological parameters on findings, listing recommendations fora «best practice» of research. Although, over the past decades, violence against women surveys have become more and more similar -tending towards a sort of uniformization that could be interpreted as a passive consensus -these instruments retain more or less subtle differences that are still susceptible to influence the validity of a comparison. Yet, only a small number of studies have directly worked on the comparability of violence against women data, striving to control the methodological parameters of the surveys in order to guarantee the validity of their comparisons. The goal of this work is to compare data from two national surveys on violence against women: the Swiss component of the International Violence Against Women Survey [CH-IVAWS] and the National Violence Against Women Survey [NVAWS] administered in the United States. The choice of these studies certainly ensues from the author's affiliations; however, it is far from being trivial. Indeed, the criminological field currently endows American and Anglo-Saxon literature with a predominant space, compelling researchers from other countries to almost do the splits to interpret their results in the light of previous work or to develop effective interventions in their own context. Turning to hypotheses or concepts developed in a specific framework inevitably raises the issue of their applicability to another context, i.e. the Swiss context, if not at least European. This problematic then takes on an interest that goes beyond the particular topic of violence against women, adding to its relevance. This work articulates around three axes. First, it shows the way survey characteristics influence estimates. The comparability of the nature of the CH-IVAWS and NVAWS, their sampling design and the characteristics of their administration are discussed. The definitions used, the operationalization of variables based on comparable items, the control of reference periods, as well as the nature of the victim-offender relationship are included among controlled factors. This study establishes content validity within and across studies, presenting a systematic process destined to maximize the comparability of secondary data. Implications of the process are illustrated with the successive presentation of comparable and non-comparable operationalizations of computed variables. Measuring violence against. women in Switzerland and the United-States, this work compares the prevalence of different forms (threats, physical violence and sexual violence) and types of violence (partner and nonpartner violence). Second, it endeavors to analyze concepts of multivictimization (i.e. experiencing different forms of victimization), repeat victimization (i.e. experiencing the same form of violence more than once), and revictimization (i.e. the link between childhood and adulthood victimization) in a comparative -and comparable -approach. Third, aiming at understanding why partner violence appears higher in the United States, while victims of nonpartners are more frequent in Switzerland, as well as in other European countries, different victimization correlates are examined. This research contributes to a better understanding of the relevance of controlling methodological parameters in comparisons across studies, as it illustrates, systematically, the imposed controls and their implications on quantitative data. Moreover, it details how ignoring these parameters might lead to erroneous conclusions, statistically as well as theoretically. The conclusion of the study puts into a wider perspective the discussion of differences and similarities of violence against women in Switzerland and the United States, and integrates recommendations as to the relevance and validity of international comparisons, whatever the'field they are conducted in. Résumé: Les comparaisons internationales dans le domaine de la victimisation, et plus particulièrement en ce qui concerne les violences envers les femmes, se caractérisent par des problèmes méthodologiques que les recherches antérieures n'ont pas systématiquement adressés, et dont la réponse ne semble pas connaître de consensus. Pour des raisons logistiques et financières évidentes, les études internationales sur les violences envers les femmes (c.-à-d. les études utilisant un même instrument dans différents pays) sont rares, aussi les chercheurs sont-ils contraints de se tourner vers des comparaisons secondaires. Beaucoup de recherches juxtaposent alors simplement leurs résultats à ceux de travaux antérieurs ou à des résultats obtenus dans d'autres contextes, afin d'offrir à leurs conclusions une perspective prétendument comparative. Si, le plus souvent, les auteurs indiquent les limites méthodologiques d'une comparaison directe, il est fréquent que ces dernières ne se traduisent pas par des contrôles méthodologiques concrets. Et pourtant, quantité de travaux ont mis en évidence l'influence des paramètres méthodologiques des enquêtes sur les résultats obtenus, érigeant des listes de recommandations pour une «meilleure pratique» de la recherche. Bien que, ces dernières décennies, les sondages sur les violences envers les femmes soient devenus de plus en plus similaires -tendant, vers une certaine uniformisation que l'on peut interpréter comme un consensus passif-, il n'en demeure pas moins que ces instruments possèdent des différences plus ou moins subtiles, mais toujours susceptibles d'influencer la validité d'une comparaison. Pourtant, seules quelques recherches ont directement travaillé sur la comparabilité des données sur les violences envers les femmes, ayant à coeur de contrôler les paramètres méthodologiques des études utilisées afin de garantir la validité de leurs comparaisons. L'objectif de ce travail est la comparaison des données de deux sondages nationaux sur les violences envers les femmes: le composant suisse de l'International Violence Against Women Survey [CHIVAWSj et le National Violence Against Women Survey [NVAWS) administré aux États-Unis. Le choix de ces deux études découle certes des affiliations de l'auteure, cependant il est loin d'être anodin. Le champ criminologique actuel confère, en effet, une place prépondérante à la littérature américaine et anglo-saxonne, contraignant ainsi les chercheurs d'autres pays à un exercice proche du grand écart pour interpréter leurs résultats à la lumière des travaux antérieurs ou développer des interventions efficaces dans leur propre contexte. Le fait de recourir à des hypothèses et des concepts développés dans un cadre spécifique pose inévitablement la question de leur applicabilité à un autre contexte, soit ici le contexte suisse, sinon du moins européen. Cette problématique revêt alors un intérêt qui dépasse la thématique spécifique des violences envers les femmes, ce qui ajoute à sa pertinence. Ce travail s'articule autour de trois axes. Premièrement, il met en évidence la manière dont les caractéristiques d'un sondage influencent les estimations qui en découlent. La comparabilité de la nature du CH-IVAWS et du NVAWS, de leur processus d'échantillonnage et des caractéristiques de leur administration est discutée. Les définitions utilisées, l'opérationnalisation des variables sur la base d'items comparables, le contrôle des périodes de référence, ainsi que la nature de la relation victime-auteur figurent également parmi les facteurs contrôlés. Ce travail établit ainsi la validité de contenu intra- et inter-études, offrant un processus systématique destiné à maximiser la comparabilité des données secondaires. Les implications de cette démarche sont illustrées avec la présentation successive d'opérationnalisations comparables et non-comparables des variables construites. Mesurant les violences envers les femmes en Suisse et aux États-Unis, ce travail compare la prévalence de plusieurs formes (menaces, violences physiques et violences sexuelles) et types de violence (violences partenaires et non-partenaires). 11 s'attache également à analyser les concepts de multivictimisation (c.-à-d. le fait de subir plusieurs formes de victimisation), victimisation répétée (c.-à.-d. le fait de subir plusieurs incidents de même forme) et revictimisation (c.-à-d. le lien entre la victimisation dans l'enfance et à l'âge adulte) dans une approche comparative - et comparable. Dans un troisième temps, cherchant à comprendre pourquoi la violence des partenaires apparaît plus fréquente aux États-Unis, tandis que les victimes de non-partenaires sont plus nombreuses en Suisse, et dans d'autres pays européens, différents facteurs associés à la victimisation sont évalués. Cette recherche participe d'une meilleure compréhension de la pertinence du contrôle des paramètres méthodologiques dans les comparaisons entre études puisqu'elle illustre, pas à pas, les contrôles imposés et leurs effets sur les données quantitatives, et surtout comment l'ignorance de ces paramètres peut conduire à des conclusions erronées, tant statistiquement que théoriquement. La conclusion replace, dans un contexte plus large, la discussion des différences et des similitudes observées quant à la prévalence des violences envers les femmes en Suisse et aux États-Unis, et intègre des recommandations quant à la pertinence et à la validité des comparaisons internationales, cela quel que soit le domaine considéré.

Pediatric CT: how to compare the Present DRL Values? : 12.10

Purpose: To determine dose thresholds, in term of CTDIvol, where subtle anatomical structures of pediatric CT images becomes no more detectable and compare them to the most recent Reference Dose Levels (DRL) proposed in the UK, Germany and Switzerland. Materials and methods: A GE LightSpeed-Ultra scanner (MSCT 8 slices) was used to perform chest and abdomen acquisitions on 8 patients (age range 2 to 16 years old) to provide a set of gold standard images. Dose reductions were then simulated by introducing image noise on raw data to provide simulated CT images with CTDIvol ranging from 2 to 22 mGy. All images were reviewed and scored independently by four experienced radiologists using the VGA methodology (Visual Grading Analysis) to determine the dose threshold where a significant loss of normal anatomy conspicuity appeared. Data were analyzed with ANOVA and Tukey HSD tests, a p >0.05 was considered to be significant. Results: No significant difference in VGA scoring appeared for CTDIvol leading to image noise levels lower than 10 and 25 HU for respectively abdominal and chest acquisitions. These data can thus be used to set the AEC (automatic exposure control) system of units having similar noise properties than the GE LightSpeed-Ultra used in this study. The present DRLs proposed for pediatric CT acquisitions are compatible with an excellent image quality level. Conclusion: The differences of DRL values proposed in Europe for pediatric acquisitions are marginal and assure a very good image quality level. The results of this study allow to further optimize the acquisition protocol by giving Noise Index value to set the AEC device.

Alcohol-attributable mortality in Switzerland in 2011--age-specific causes of death and impact of heavy versus non-heavy drinking.

BACKGROUND: Alcohol use causes high burden of disease and injury globally. Switzerland has a high consumption of alcohol, almost twice the global average. Alcohol-attributable deaths and years of life lost in Switzerland were estimated by age and sex for the year 2011. Additionally, the impact of heavy drinking (40+grams/day for women and 60+g/day for men) was estimated. METHODS: Alcohol consumption estimates were based on the Addiction Monitoring in Switzerland study and were adjusted to per capita consumption based on sales data. Mortality data were taken from the Swiss mortality register. Methodology of the Comparative Risk Assessment for alcohol was used to estimate alcohol-attributable fractions. RESULTS: Alcohol use caused 1,600 (95% CI: 1,472 - 1,728) net deaths (1,768 deaths caused, 168 deaths prevented) among 15 to 74 year olds, corresponding to 8.7% of all deaths (men: 1,181 deaths; women: 419 deaths). Overall, 42,627 years of life (9.7%, 95% CI: 40,245 - 45,008) were lost due to alcohol. Main causes of alcohol-attributable mortality were injuries at younger ages (15-34 years), with increasing age digestive diseases (mainly liver cirrhosis) and cancers (particularly breast cancers among women). The majority (62%) of all alcohol-attributable deaths was caused by chronic heavy drinking (men: 67%; women: 48 %). CONCLUSION: Alcohol is a major cause of premature mortality in Switzerland. Its impact, among young people mainly via injuries, among men mainly through heavy drinking, calls for a mix of preventive actions targeting chronic heavy drinking, binge drinking and mean consumption.

El origen de la construcción fenomenalista: Mach, Moore y Whitehead

It's usually believed that the idea of applying logical methods to constructivist phenomenalism was, --in general- a result of Russell's originality. In this paper is argued that some important ideas were in fact due to Mach, Moore and Whitehead. According to the author, Russell got from Mach the general idea of epistemology as an analysis of scientific concepts and, specially,the idea of sensations as the building blocks for his logical construction. Moore made Russell believe that only sensations are known in a direct way, and so, the existence of external objects as the cause of our perceptions is only inferred. Moreover, according to the author, Russell's views on sense data -his sensibilia- are also due to Moore. Finally, Russell got from Whitehead the idea of the phenomenical reconstruction as an alternative to the causal theory of perception, and also how the logical construction should be done. The author undertakes also a detailed analysis of some early works of Whitehead not very well known.

Mineralocorticoid Receptor Antagonism in the Treatment of Chronic Central Serous Chorioretinopathy : A Pilot Study.

PURPOSE:: Based on experimental data showing that central serous chorioretinopathy could result from overactivation of mineralocorticoid receptor pathway in choroid vessels, the authors studied eplerenone, a mineralocorticoid receptor antagonist, as a potential treatment for chronic central serous chorioretinopathy. METHODS:: This nonrandomized pilot study included 13 patients with central serous chorioretinopathy of at least 4-month duration, treated with 25 mg/day of oral eplerenone for a week followed by 50 mg/day for 1 or 3 months. The primary outcome measure was the changes in central macular thickness recorded by optical coherence tomography, and the secondary outcomes included changes in foveal subretinal fluid (SRF) measured by OCT, in best-corrected visual acuity (BCVA) and the percentage of eyes achieving complete resolution of subretinal fluid during the treatment period. RESULTS:: Central macular thickness decreased significantly from 352 ± 139 μm at baseline to 246 ± 113 μm and 189 ± 99 μm at 1 and 3 months under eplerenone treatment (P < 0.05 and P < 0.01, respectively). At 3 months, the subretinal fluid significantly decreased compared with baseline subretinal fluid (P < 0.01) and best-corrected visual acuity significantly improved compared with baseline best-corrected visual acuity (P < 0.001). CONCLUSION:: Eplerenone treatment was associated with a significant reduction in central macular thickness, subretinal fluid level, and an improvement in visual acuity. Randomized controlled trials are needed to confirm these encouraging results.

Fourth cranial nerve palsy and brown syndrome: two interrelated congenital cranial dysinnervation disorders?

Based on neuroimaging data showing absence of the trochlear nerve, congenital superior oblique palsy is now classified as a congenital cranial dysinnervation disorder. A similar absence of the abducens nerve is accompanied by misinnervation to the lateral rectus muscle from a branch of oculomotor nerve in the Duane retraction syndrome. This similarity raises the question of whether some cases of Brown syndrome could arise from a similar synkinesis between the inferior and superior oblique muscles in the setting of congenital superior oblique palsy. This hypothesis has gained support from the confluence of evidence from a number of independent studies. Using Duane syndrome as a model, we critically review the accumulating evidence that some cases of Brown syndrome are ultimately attributable to dysgenesis of the trochlear nerve.

Concrete Pavement Mixture Design and Analysis (MDA): Assessment of Air Void System Requirements for Durable Concrete, TPF-5(205), 2012

Concrete will suffer frost damage when saturated and subjected to freezing temperatures. Frost-durable concrete can be produced if a specialized surfactant, also known as an air-entraining admixture (AEA), is added during mixing to stabilize microscopic air voids. Small and well-dispersed air voids are critical to produce frost-resistant concrete. Work completed by Klieger in 1952 found the minimum volume of air required to consistently ensure frost durability in a concrete mixture subjected to rapid freezing and thawing cycles. He suggested that frost durability was provided if 18 percent air was created in the paste. This is the basis of current practice despite the tests being conducted on materials that are no longer available using tests that are different from those in use today. Based on the data presented, it was found that a minimum air content of 3.5 percent in the concrete and 11.0 percent in the paste should yield concrete durable in the ASTM C 666 with modern AEAs and low or no lignosulfonate water reducers (WRs). Limited data suggests that mixtures with a higher dosage of lignosulfonate will need about 1 percent more air in the concrete or 3 percent more air in the paste for the materials and procedures used. A spacing factor of 0.008 in. was still found to be necessary to provide frost durability for the mixtures investigated.

Canonical WNT signaling in hematopoiesis and leukemia

SummaryCanonical Wnt signaling is crucial for embryonic development and the homeostasis of certain adult tissues such as the gut and the skin. The role of canonical Wnt signaling in hematopoiesis is still debated. The expression of a dominant-active β-catenin in hematopoietic stem cells (HSCs) enhances the self-renewal capacity of HSCs but is detrimental for long-term hematopoiesis. In contrast, loss of function experiments show that absence of β- and γ-catenin does not impair steady-state hematopoiesis. It has been argued that the inducible deletion of β-catenin using the IFN-responsive Mx promoter may somehow influence stem cell fate. Herein we used the constitutive deletion of β-catenin specifically in hematopoietic cells to show that the absence of β- catenin, as well as γ-catenin deletion, does not impair normal hematopoiesis and self-renewal capacity of HSCs.Dysregulation of canonical Wnt signaling is causal for several types of cancer, including colon carcinoma or breast cancer. Recently, it was found that Wnt signal transduction was upregulated in certain leukemias. Based on these data, we have investigated whether β- and γ-catenin play a role for the induction of leukemias by oncogenic BCR-ABL translocation product. We show that the induction of B-ALL (B cell acute lymphocytic leukemia) is strongly reduced in the absence of γ-catenin, while the induction of CML (chronic myeloid leukemia) occurs at a normal rate. In the combined absence of β- and γ-catenin the induction of both CML and B-ALL is essentially blocked. Consistent with these data others have found that β-catenin is essential for the induction of CML by BCR-ABL.Collectively, we find that β- and γ-catenin are dispensable for normal hematopoiesis but essential for the development of BCR-ABL induced leukemias. These findings suggest that the canonical Wnt pathway may represent a promising target for the therapy of leukemia.RésuméLa voie de signalisation canonique Wnt est essentielle pour le développement embryonnaire ainsi que l'homéostasie de certains tissus adultes, comme les intestins et la peau. Le rôle de la voie canonique Wnt pour l'hématopoïèse est encore incertain. D'un coté l'expression d'une forme active de β-catenine dans les cellules souches de la moelle augmente leur potentiel d'auto- renouvellement mais est préjudiciable pour l'hématopoïèse à long terme. Par contre, l'absence de β- et γ-catenine n'empêche pas le déroulement normal de l'hématopoïèse. La façon dont est supprimée β-catenine, en utilisant le promoteur IFN-inductible Mx, pourrait influencer le sort des cellules souches. Ici nous détruisons β-catenine spécifiquement dans les cellules hématopoïétiques de manière constitutive et montrons que, en combinaison avec l'absence de γ-catenine, l'absence de β-catenine n'affecte pas le déroulement normal de l'hématopoïèse et la capacité des cellules souches de la moelle à se renouveler.Plusieurs sortes de cancers, comme celui du colon ou du sein, sont parfois dus à une dérégulation de la voie canonique Wnt. Récemment, certaines leucémies ont présenté une activation du signal Wnt. A partir de ces données, nous avons examiné si β- et γ-catenine jouent un rôle dans l'induction des leucémies causées par le produit de translocation BCR-ABL. Nous avons montré que l'induction de la leucémie aiguë lymphoïde de cellules Β (LAL-B) est grandement diminuée en l'absence de γ-catenin, alors que l'induction de la leucémie myéloïde chronique (LMC) n'est pas affectée. En l'absence des deux catenines, l'induction des deux leucémies LAL-B et LMC est presque complètement bloquée. En confirmation de nos données, un autre groupe a montré que β-catenine est essentielle pour le développement de la LMC. Ensemble, ces données nous montrent que β- et γ-catenine ne sont pas nécessaires pour l'hématopoïèse normale, mais essentielle pour le développement des leucémies induites par BCR-ABL. Cela suggère que la voie de signalisation canonique Wnt est une cible prometteuse pour de futures thérapies.