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Relative Risk (RR), Odds Ratio (OR) and Hazard Ratio (HR).
Odds ratio (OR) is a statistic commonly encountered in professional or scientific medical literature. Most readers perceive it as relative risk (RR), although most of them do not know why that would be true. But since such perception is mostly correct, there is nothing (or almost nothing) wrong with that. It is nevertheless useful to be reminded now and then what is the relation between the relative risk and the odds ratio, and when by equating the two statistics we are sometimes forcing OR to be something it is not. Another statistic which is often also perceived as a relative risk is the hazard ratio (HR). We encounter it, for example, when we fit the Cox model to survival data. Under proportional hazards it is probably "natural" to think in the following way: if the probability of death in one group is at every time point k-times as high as the probability of death in another group, then the relative risk must be k, regardless of where in time we are. Well, we shall see if this is true
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Common cancer types aggregate in families.
The discussion on the specific roles of heredity and environment in these aggregations has been restricted by the limited amount of available empiric data combined with an incomplete understanding of the tumorigenic process. Several major advances have recently provided the potential to explore a large fraction of the human genome diversity, making effective the search for association while requiring minimal functional hypotheses. Since 2006, the genotyping of sets of DNAs on hundreds of thousand of loci has become routine practice, thus opening the Genome Wide Association Studies era. More than three hundred publications describing results of GWAS studies have now been published providing a better view on the mechanism by which genetic diversity may modulate human phenotype and disease risk. GWAS for susceptibility to over twenty different cancer types have been performed unraveling for each of type one to dozens of susceptibility loci. Observations of multiple independent hits in the same region are not infrequent with the most striking example being a 500 kb region, in the vicinity of the MYC oncogene, which harbors multiple susceptibility loci for at least 4 different cancer types. Occasionally the same susceptibility locus may be shared with other trait/disease suggesting etiological relationships. Allele specific odd ratios for common cancer are usually small (i.e. less than 1.5). There is mounting evidence that common polymorphism will only explain a small fraction of the heritability of common diseases. A complementary hypothesis posits that a substantial part of this heritability is due to many, genetically independent, rare mutations, a proposition that has recently gained experimental support. Although some of the cancer-associated markers are located within or in proximity of genes with conspicuous functional relevance to cancer, other loci are distant from any characterized gene and the altered functions remain elusive. Taking advantage of the new generation sequencing technology, search for very rare variants in candidate functional regions may provide an effective identification strategy. In contrast, definite identification of the actual genetic variation which is directly responsible for the observed association in the initial GWAS oppose major difficulties due to the presence of strong local linkage disequilibrium. GWAS and their follow-up studies still lack power to conclusively evaluate the role of gene/gene and gene/environment interaction in defining individual cancer risk. This lack of information obscures the delineation of the place that DNA typing will occupy in cancer prevention or early detection programs. .
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"The common language of mutualism and pathogenic animal-microbial associations: Lessons from the squid-vibrio system"
One of the principal questions in the study of animal-bacterial interactions is: What are the cellular and molecular differences between beneficial and pathogenic associations? The study of several invertebrate symbioses has demonstrated that, although the outcomes are different, beneficial and pathogenic assocations share much of the same molecular language. This presentation will focus upon contributions to the field made by the study of the relationship between the Hawaiian bobtail squid Euprymna scolopes and its luminous bacterial partner Vibrio fischeri. In this symbiosis, the bacteria are acquired anew each generation and form persistent interactions along the apical surfaces of host epithelia, a pattern of symbiosis that is perhaps the most widespread among animals. The mechanisms underlying the processes of host-symbiont recognition, induction of partner development, and the maintenance of a balanced relationship will be highlighted.
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Effets de radionucléides sur le budget énergétique et la dynamique de population de Daphnia magna
La contamination à l'uranium appauvri et l'américium-241 représente respectivement une exposition à un métal lourd, dont la toxicité chimique domine largement le stress radiologique, et une irradiation alpha interne. Les effets de ces radionucléides ont été récemment étudiés sur plusieurs générations successives chez le microcrustacé Daphnia magna, afin d'évaluer le risque écologique lié à la présence de ces radionucléides dans les écosystèmes aquatiques. De nombreuses perturbations de l'histoire de vie (survie, fécondité, âge de maturité) et de la physiologie (nutrition, respiration, croissance en taille et masse) des daphnies, variables en fonction du contaminant considéré, de la concentration ou de la dose radiologique subie et de la durée d'exposition, ont ainsi été mises en évidence en conditions controlées au laboratoire. L'approche est pertinente sur un plan toxicologique et à l'échelle de l'organisme, tandis que les conséquences au niveau d'une population dans un contexte écologique réaliste sont plus difficiles à appréhender. Cette difficulté tient en autre au fait que les populations en milieu naturel sont constamment soumises aux variations des conditions environnementales - notamment de la ressource - qui altèrent leur capacité à survivre, croître et faire face à la toxicité des polluants. Différents modèles énergétiques (DEBtox, Production Nette) sont considérés pour simuler la dynamique de population de D. magna exposé aux différents radionucléides. Ces modèles individu-centrés décrivent l'acquisition de l'énergie via la nutrition et son allocation à la survie, la croissance et la reproduction. L'approche repose sur l'hypothèse que toute perturbation de l'acquisition d'énergie ou du coût métabolique de la survie induite par les contaminants, intervient au dépens des processus importants pour la croissance de population. On examine en particulier l'importance de prendre en compte une dynamique individuelle réaliste (la croissance lors de cycles de mues successifs dans le cas de Daphnia) pour modéliser les processus physiologiques. A terme, les modèles doivent permettre de tester à quel degré les contraintes naturelles du milieu peuvent influencer la réponse des organismes et des populations aux polluants chimiques et radiologiques.Séminaire en Français - Seminar in French
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Ce qui est observé et ce qui est caché, ce qui est quantifiable et ce qui ne l'est pas: Réflexion d'un biostatisticien avant l'été.
Le Biostatisticien dispose de données observées qui agissent sur son objet d'étude mais il doit prendre en compte l'existence d'autres facteurs, non observés, agissant eux aussi. En production industrielle, la quantification semble appropriée et suffisante pour évaluer le processus de fabrication. Ce n'est pas le cas en biologie à cause d'une part de la diversité qui règne dans le vivant et d'autre part sur les effets d'amplification diverses chez le vivant plus que la matière inerte.Contact: Mme Mariethé CHAUMEIL Inscription gratuite mais obligatoire avant le lundi 07 juin 2010 Courriel: mariethe.chaumeil@chu-lyon.fr
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On the genetic architecture of Cytoplasmic Incompatibility: inference from phenotypic data
In the absence of a clear understanding of its genetic basis, Cytoplasmic Incompatibility (CI) has so far been conceptualized using a simple toxin-antitoxin model. Under this model, a symbiont's ³compatibility type² is determined by the specific interaction between two components: a modification factor (mod, expressed in sperm) and a rescue factor (resc, expressed in the eggs). Here we confront this model to a well studied, complex and puzzling CI study system: the mosquito Culex pipiens. We show that a more elaborate model is required to account for the observed pattern, including multiple mod and resc genes, and possibly quantitative variation in gene products. We develop such a model and fit its parameters to the data using a parsimony approach. We thereby produce explicit predictions with regards to the genetic architecture of CI; namely, we infer that at least five mod / resc pairs are required to explain the data. These predictions provide a starting point for future genetic and genomic analyses of CI and will hopefully contribute to the decryption of its molecular basis.
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Brown algae, multicellularity and sex
Susana Coelho will present a paper recently published in Nature by an international consortium coordinated by Roscoff on the Ectocarpus genome and the independent evolution of multicellularity in brown algae. Denis Roze will present his theoretical work on deleterious mutations and selection for sex and recombination.
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Mechanistic effect models for ecological risk assessment of chemicals: CREAM and the documentation framework TRACE
Population-level effects of chemicals, for example pesticides, depend not only on exposure and toxicity but also on ecological factors. It is impossible to fully address these factors empirically. Mechanistic effect models, for example ecological models, can solve this problem. They can be used to extrapolate results from single species tests and higher tier tests to the population level and larger scales. Currently, however, there is no common framework that would allow developing such models and assessing their quality in a coherent way. The EU-funded project CREAM ("Mechanistic Effect Models for Ecological Risk Assessments of Chemicals") aims at developing and establishing such a framework. CREAM will not only focus on what Good Modelling Practice is but also on how it can be developed and established. CREAM's central approach will be to use a common framework for documenting the modelling process, dubbed TRACE (Transparent Comprehensive Modelling) documentation. TRACE provides a common structure for organizing and, at the same time, documenting the modelling process on a day-to-day basis. I will demonstrate the use of TRACE using example models. Finally, I will discuss a main further challeng of ecological modelling for chemical risk assessment: the agreement on practical but meaningful population-level endpoints.See the two regional speakers on the SEMOVI web page : http://www.cgmc.univ-lyon1.fr/Semovi/
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Analyse statistique des risques concurrents
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Aspects of dose-response modelling
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L'analyse critique des essais randomisés d'un programme de dépistage : nà propos des derniers essais de dépistage du cancer de la prostate.
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Are bigger brains better?
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"Stirring Tails of Evolution"
One of the most fundamental issues in biology is the nature of evolutionary transitions from single cell organisms to multicellular ones. Not surprisingly for microscopic life in a fluid environment, many of the processes involved are related to transport and locomotion, for efficient exchange of chemical species with the environment is one of the most basic features of life. This is particularly so in the case of flagellated eukaryotes such as green algae, whose members serve as model organisms for the study of transitions to multicellularity. In this talk I will summarize recent theoretical and experimental work addressing a number of interrelated aspects of evolutionary transitions in the Volvocine green algae, which range from unicellular Chlamydomonas to Volvox , with thousands of cells. Phenomena to be discussed include allometry of nutrient uptake, phenotypic plasticity, flagellar synchronization, hydrodynamic bound states, and the dynamics of adaptive phototaxis.For more details, see http://www.cgmc.univ-lyon1.fr/Semovi/13octobre2010.php
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"The mutations responsible for phenotypic evolution : from single casenstudies to general rules"
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Information use, habitat selection and breeding performance in anlandscape of fear
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Systematic protein-genome interaction maps reveal 5 chromatin types in Drosophila.
The local protein composition of chromatin controls important processes such as transcription, replication and DNA repair, yet the diversity of chromatin and its distribution along chromosomes is still poorly characterized.Using DamID in Drosophila Kc cells, we generated high-resolution genome-wide binding maps of 53 chromatin proteins from a wide range of functional categories. For most of those proteins, no binding data was previously available.By constructing a non supervised classifier, we find that there are five principal chromatin types defined by unique yet overlapping combinations of proteins.Two types correspond to Polycomb and HP1-bound regions, respectively. The novel 'BLACK' chromatin type covers half of the genome and induces strong transcriptional repression on inserted transgenes. Remarkably, this chromatin type is devoid of the classic 'heterochromatin' proteins Polycomb and HP1. Thus, our data reveal the existence of a prominent repressive chromatin type that has largely been overlooked.Active genes are associated with one of the other two remaining combinations of proteins. H3K36 methylation is associated with only one of them, yet it was previously thought to mark every transcribed gene. In addition, active genes involved in growth and cell proliferation, and those involved in signal transduction are located in a distinct chromatin types.The five chromatin types modulate the interactions of transcription factors with DNA. We observe that most transcription factors bind their cognate motif only if it sits in the favored chromatin context. Our data rule out a simple exclusion mechanism but support a model whereby synergistic interactions target transcription factors to their binding site.Finally, genomic regions in the 5 chromatin types follow different evolutionary processes. The vast majority of synteny breaks with Drosophila pseudoobscura occurs in only one of the transcriptionally active types. Besides, the speed of evolution of genes located in that chromatin type is higher than for other types.In summary, our integrative approach identifies five major chromatin types, which are defined by unique combinations of proteins and have distinct functional properties.
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The evolution of an informed based dispersal
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La recherche médicale a-t-elle besoin de mathématiques? L'exemple de l'épidémiologie descriptive
L'intervention des mathématiques dans la recherche médicale a eu des fortunes diverses au cours de l'histoire. Si à la fin du 18ième siècle les chercheurs français, comme Gavaret et Louis ont montré la voie en utilisant des outils forgés par Laplace, et enseignés par Poisson à l'école polytechnique pour évaluer l'efficacité des thérapeutiques, l'histoire récente suggère plutôt un divorce entre les deux disciplines dans notre pays, où le malentendu a sans doute son origine dans les diatribes de Claude Bernard contre les statistiques grossières faites par les médecins de son temps. En prenant l'exemple de l'épidémiologie descriptive, souvent considérée comme la moins sophistiquée des disciplines médicales, on peut montrer que la modélisation mathématique y a une importance capitale. Elle permet par exemple de juger objectivement la valeur d'un programme de dépistage ou l'impact des progrès thérapeutiques sur la survie des cancers. Aujourd'hui comme hier cette approche demande une collaboration entre professionnels des deux disciplines partageant leurs points de vue et leurs méthodes et prêts à fonder leurs progrès sur une base de connaissances communes. La disponibilité croissante de ressources informatiques sera de faible utilité si on oublie que les modèles mathématiques reposent d'abord sur la création de concepts adaptés à la discipline à laquelle on envisage de les appliquer.
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Deep divergences of human gene trees and models of human origins
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Les mathématiques à la rescousse de la biodiversité
Pas de résumé