An ordered subset approach to including covariates in the transmission disequilibrium test

Clinical heterogeneity of a disease may reflect an underlying genetic heterogeneity, which may hinder the detection of trait loci. Consequently, many statistical methods have been developed that allow for the detection of linkage and/or association signals in the presence of heterogeneity

A new scoring system for the diagnosis of BRCA1/2 associated breast-ovarian cancer predisposition.

International audienceCriteria have been proposed for genetic testing of breast and ovarian cancer susceptibility genes BRCA1 and BRCA2. Using simulations, this study evaluates the efficiency (sensitivity, positive predictive value [PPV] and specificity) of the various criteria used in France. The efficiency of the criteria published in 1998, which are largely used, is not optimal. We show that some extensions of these criteria provide an increase in sensitivity with a low decrease in specificity and PPV. The study shows that scoring systems (Manchester, Eisinger) have similar efficiency that may be improved. In this aim, we propose a new scoring system that takes into account unaffected individuals and kinship coefficients between family members. This system increases sensitivity without affecting PPV and specificity. Finally, we propose a two-step procedure with a large screening by the physician for recommending genetic counselling, followed by a more stringent selection by the geneticist for prescribing genetic testing. This procedure would result in an increase of genetic counselling activity but would allow the identification of almost 80% of mutation carriers among affected individuals, with a mutation detection rate of 15% and a specificity of 88%

Author Correction: DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death (Scientific Reports, (2021), 11, 1, (16793), 10.1038/s41598-021-95976-7)

Link to the corrected article: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/3944

DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death

The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan–Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06–1.90) for overall mortality, and 1.94 (1.04–3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.This article has been corrected. Link to the correction: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/3975

Aspects constructifs de la théorie des corps valués (précédée d'un chapitre sur la noethérianité constructive)

L'objet principal de cette thèse est l'étude de la théorie des corps valués du point de vue des mathématiques constructives. Le mémoire débute cependant par un chapitre dédié à la noethérianité constructive; on y donne une preuve constructive du Lemme de Dickson. Le lemme de Dickson prouvant la correction de l'algorithme de Buchberger, on en déduit ensuite la noethéranité constructive (au sens de la condition de chaîne ascendante CCA de Seidenberg) de l'anneau K[X1, ..., Xn].On y donne également un autre énoncé de la noethérianité (équivalent à CCA du point de vue des mathématiques classiques, mais plus fort du point de vue constructif), dont on prouve la validité pour K[X1, ..., Xn], en utilisant une autre preuve constructive du lemme de Dickson, ainsi qu'une preuve de transfert de la noethérianité de A à A[X]. La preuve permet également de redémontrer un résultat de JACOBSON et LÖFWALL, un théorème de transfert de même nature. Ce chapitre se termine par une étude détaillée de la longueur maximale atteinte par des chaînes croissantes d'idéaux de type fini. La suite du mémoire présente quelques points généraux de la théorie des corps valués, puis décrit de façon détaillée la construction du hensélisé d'un corps valué, dans l'esprit de travaux précédents dûs à Franz-Viktor KUHLMANN et Henri LOMBARDI ; des versions constructives des théorèmes classiques concernant les corps henséliens sont données. On donne également une construction du corps d'inertie et du hensélisé strict d'un corps valué. Le chapitre IV donne une variante du lemme de Hensel due à Sudesh K. KHANDUJA et Jayanti SAHA, qui n'avait été démontrée que dans le cas des corps complets de valuation discrète. Le chapitre V présente des travaux effectués en collaboration avec Henri LOMBARDI et Franz-Viktor KUHLMANN; il s'agit d'algorithmes de calcul dynamique dans la clôture algébrique d'un corps valué, dans l'esprit de l'agorithme D5 de Jean DELLA-DORA, Claire DICRESCENZO et Dominique DUVAL j ces algorithmes permettent de donner une élimination des quantificateurs dans les corps valués algébriquement clos, bien différente de celle précédemment donnée par Volker WEISPFENNING.BESANCON-BU Sciences Staps (250562103) / SudocSudocFranceF

Space Alternating Penalized Kullback Proximal Point Algorithms for Maximing Likelihood with Nondifferentiable Penalty

The EM algorithm is a widely used methodology for penalized likelihood estimation. Provable monotonicity and convergence are the hallmarks of the EM algorithm and these properties are well established for smooth likelihood and smooth penalty functions. However, many relaxed versions of variable selection penalties are not smooth. The goal of this paper is to introduce a new class of Space Alternating Penalized Kullback Proximal extensions of the EM algorithm for nonsmooth likelihood inference. We show that the cluster points of the new method are stationary points even when on the boundary of the parameter set. Special attention has been paid to the construction of component-wise version of the method in order to ease the implementation for complicated models. Illustration for the problems of model selection for finite mixtures of regression and to sparse image reconstruction is presented

Modeling the effect of PTPN22 in rheumatoid arthritis.

International audienceABSTRACT : In order to model the effect of PTPN22 on rheumatoid arthritis (RA), we determined the combination of single-nucleotide-polymorphisms (SNPs) showing the strongest association with RA. Three SNPs (rs2476601-rs12730735-rs11102685) were selected for which we estimated the genotypic relative risks (GRRs) of the corresponding genotypes. On the basis of these GRRs we defined four at-risk genotypic classes. Relative to the class of reference risk, individuals had a risk approximately multiplied by two, three, or four. This classification was confirmed by the excess of identity-by-descent (IBD) sharing (IBD = 2) for the sibs of an index in the high-risk class and by excess of non-IBD sharing (IBD = 0) when the index belonged to the low-risk class. The observed data could not be explained by the role of a single variant but were compatible either with a joint effect of the three typed SNPs of PTPN22 on RA or with the role of two untyped variants