Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood

BACKGROUND: Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. OBJECTIVE: Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. METHODS: We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totaling 8,273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analyzed. RESULTS: The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P=4.3x10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P<5x10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P=4.9x10-7 ), 14q22 (rs7493885 near NIN; P=2.9x10-6 ) and 2p22 (rs232542 near CYP1B1; P=4.1x10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings. CONCLUSION AND CLINICAL RELEVANCE: We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms. This article is protected by copyright. All rights reserved

Design and Reliability Performance Evaluation of Network Coding Schemes for Lossy Wireless Networks

This thesis investigates lossy wireless networks, which are wireless communication networks consisting of lossy wireless links, where the packet transmission via a lossy wireless link is successful with a certain value of probability. In particular, this thesis analyses all-to-all broadcast in lossy wireless networks, where every node has a native packet to transmit to all other nodes in the network. A challenge of all-to-all broadcast in lossy wireless networks is the reliability, which is defined as the probability that every node in the network successfully obtains a copy of the native packets of all other nodes. In this thesis, two novel network coding schemes are proposed, which are the neighbour network coding scheme and the random neighbour network coding scheme. In the two proposed network coding schemes, a node may perform a bit-wise exclusive or (XOR) operation to combine the native packet of itself and the native packet of its neighbour, called the coding neighbour, into an XOR coded packet. The reliability of all-to-all broadcast under both the proposed network coding schemes is investigated analytically using Markov chains. It is shown that the reliability of all-to-all broadcast can be improved considerably by employing the proposed network coding schemes, compared with non-coded networks with the same link conditions, i.e. same probabilities of successful packet transmission via wireless channels. Further, the proposed schemes take the link conditions of each node into account to maximise the reliability of a given network. To be more precise, the first scheme proposes the optimal coding neighbour selection method while the second scheme introduces a tuning parameter to control the probability that a node performs network coding at each transmission. The observation that channel condition can have a significant impact on the performance of network coding schemes is expected to be applicable to other network coding schemes for lossy wireless networks

Genome-wide association and Meta-analysis of age at onset in Parkinson Disease

Background and Objectives Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10−8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10−9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = −0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10−8). Discussion Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). Conclusions We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA

Le problème des hydrates dans le contexte de la production et du transport polyphasiques des pétroles bruts et des gaz naturels. Deuxième partie : les solutions possibles aux difficultés d'exploitation générées par les hydrates Hydrates Problem Within the Framework of Multiphase Production and Transport of Crude Oils and Natural Gases. Part Two: Possible Solutions to Exploitation Difficulties Generated by Hydrates

L'exploitation en mer des gisements de combustibles fossiles fluides a amplifié le besoin d'accroître nos connaissances sur les hydrates qui sont susceptibles de boucher les installations de production, de traitement et de transport. La première partie rappelait la structure moléculaire des hydrates I, Il et H et décrivait ensuite succinctement l'analyse physico-chimique de leur formation, tant sur les plans thermodynamique que cinétique. Dans cette deuxième partie, les remèdes possibles aux problèmes rencontrés par les compagnies opératrices sont indiqués, essentiellement les inhibiteurs thermodynamiques classiques tels que les alcools ou les sels qui diminuent la température de formation des hydrates, et les additifs dispersants qui évitent la croissance et/ou l'agglomération des cristaux. Pour terminer, une boucle pilote de circulation originale est présentée, ses caractéristiques qui permettent la validation des additifs dispersants dans des conditions hydrodynamiques et physico-chimiques représentatives étant soulignées. Offshore exploitation of fossil fluid fuels has emphasized the need of improving our knowledge on hydrates which can plug production, treatment and transport facilities. The first part recalled the molecular structure of I, II and H hydrates, then the physical-chemistry of their formation was briefly reviewed from both the thermodynamic and the kinetic points of view. In this second part, the possible remedies to the problems met by operating companies are described, mainly classical thermodynamic inhibitors such as alcohols or salts which decrease the hydrates formation temperature, and dispersant additives which avoid crystals growth and/or agglomeration. At last an original circulation loop at pilot scale is presented, its characteristics which allow the testing of dispersant additives under representative hydrodynamic and physico-chemical conditions being outlined

Le problème des hydrates dans le contexte de la production et du transport polyphasiques des pétroles bruts et des gaz naturels. Deuxième partie : les solutions possibles aux difficultés d'exploitation générées par les hydrates

L'exploitation en mer des gisements de combustibles fossiles fluides a amplifié le besoin d'accroître nos connaissances sur les hydrates qui sont susceptibles de boucher les installations de production, de traitement et de transport. La première partie rappelait la structure moléculaire des hydrates I, Il et H et décrivait ensuite succinctement l'analyse physico-chimique de leur formation, tant sur les plans thermodynamique que cinétique. Dans cette deuxième partie, les remèdes possibles aux problèmes rencontrés par les compagnies opératrices sont indiqués, essentiellement les inhibiteurs thermodynamiques classiques tels que les alcools ou les sels qui diminuent la température de formation des hydrates, et les additifs dispersants qui évitent la croissance et/ou l'agglomération des cristaux. Pour terminer, une boucle pilote de circulation originale est présentée, ses caractéristiques qui permettent la validation des additifs dispersants dans des conditions hydrodynamiques et physico-chimiques représentatives étant soulignées

«Mises à jour» de données scientifiques suite aux recommandations du groupe radioécologie Nord-Cotentin (GRNC) formulées en 1999

Updating of scientific data following the Nord-Cotentin Radioecology Group (GRNC) recommendations expressed in 1999. In its report submitted to the ministers in 1999, the GRNC indicated the need to carry out further studies so that some gaps in the knowledge of radiological parameters are filled, and recommended to take into account aspects other than the radiological ones. Further to these recommendations, the ministers of State of Health and Environment assigned the GRNC the responsibility of a second mission (study of uncertainties on the first mission results, and consideration of chemical releases). Then, about the radiological data used, thanks to various studies recently published by the IRSN, information concerning radionuclide concentrations, not much studied until then, has been obtained and parameters have been specified. Completely new information has been acquired as chlorine-36 information. In the present text are summarized the scientific contributions obtained since the GRNC report publication. © EDP Sciences, 2004