Reduced phenotypic expression in genetic hemochromatosis with time role of exposure to nongenetic modifiers

International audienceBackground & aims - Genetic hemochromatosis is mainly related to the homozygous p.Cys282Tyr (C282Y) mutation in the HFE gene, which causes hepcidin deficiency. Its low penetrance suggests the involvement of cofactors that modulate its expression. We aimed to describe the evolution of disease presentation and of non-genetic factors liable to impact hepcidin production in the long term. Methods - Clinical symptoms, markers of iron load, and risk factors according to the year of diagnosis were recorded over 30 years in a cohort of adult C282Y homozygotes. A total of 2,050 patients (1,460 probands [804 males and 656 females] and 542 relatives [244 males and 346 females]) were studied. Results - Over time: (i) the proband-to-relative ratio remained roughly stable; (ii) the gender ratio tended towards equilibrium among probands; (iii) age at diagnosis did not change among males and increased among females; (iv) the frequency of diabetes and hepatic fibrosis steadily decreased while that of chronic fatigue and distal joint symptoms remained stable; (v) transferrin saturation, serum ferritin and the amount of iron removed decreased; and (vi) the prevalence of excessive alcohol consumption decreased while that of patients who were overweight increased. Tobacco smoking was associated with increased transferrin saturation. Conclusion - Genetic testing did not alter the age at diagnosis, which contrasts with the dramatic decrease in iron load in both genders. Tobacco smoking could be involved in the extent of iron loading. Besides HFE testing, which enables the diagnosis of minor forms of the disease, the reduction of alcohol consumption and the increased frequency of overweight patients may have played a role in the decreased long-term iron load, as these factors are likely to improve hepcidin production. Lay summary - Genetic hemochromatosis is an inherited disorder that leads to progressive iron overload in the body. It results in chronic fatigue and in potential liver (cirrhosis), pancreas (diabetes) and joint (arthritis) damage in adulthood. The present study showed that tobacco smoking may aggravate iron loading, but that hemochromatosis has become less and less severe over the last 30 years despite patients being older at diagnosis, likely because of the protective effects of lower alcohol consumption and of increased weight in the French population

RÉSIF-SI : Un système d'information distribué pour les données sismologiques françaises

International audienceThe Résif project, which started in 2008, aims at gathering under a common research infrastructure the French seismological, Global Navigation Satellite Systems and gravimeter permanent networks, as well as the mobile instrument pools. A central part of Résif is its seismological information system, Système d'Information de Résif (Résif‐SI) (started in 2012), which is in charge of collecting, validating, archiving, and distributing seismological data and metadata from seven national centers. Résif‐SI follows a distributed architecture, in which the six data collection and validation centers (A‐nodes) send validated data and metadata to a national data center (Résif Data Center [Résif‐DC]), which is the central point for data archiving and distribution. Résif‐SI is based on international standard formats and protocols, and is fully integrated into European and international data exchange systems (European Integrated Data Archive, European Plate Observing System [EPOS], Incorporated Research Institutions for Seismology, International Federation of Digital Seismograph Networks). In this article, we present the organization of Résif‐SI, the technical details of its implementation, and the catalog of services provided to the end users. The article is aimed both at seismologists, who want to discover and use Résif data, and at data center operators, who might be interested in the technical choices made in the implementation of Résif‐SI. We believe that Résif‐SI can be a model for other countries facing the problem of integrating different organizations into a centralized seismological information system.Le Système d'Information sismologique de Résif (Résif-SI), dont la construction a commencé en 2012, est chargé de collecter, valider, archiver et distribuer les données et métadonnées des stations sismologiques opérés par les établissements de recherche français et leur partenaires. Il a été construit par l'intégration des infrastructures de données issues des réseaux permanents français, qui se sont fédérés au sein de Résif et ont harmonisé leurs pratiques et leurs formats d’archivage, de description et de distribution des séries temporelles sismologiques. Le résultat est une architecture distribuée organisée en six centres de collecte et de validation qui envoient les données et métadonnées validées à un centre national (Résif Data Center) qui archive et distribue l'ensemble des séries temporelles. Résif-SI est basé sur des formats et des protocoles standard internationaux, à la définition et développement desquels il participe activement. Il est entièrement intégré dans les systèmes d'échange de données européens et internationaux et constitue l’un des douze nœuds de l’archive européenne Eida (European Integrated Data Archive de l’European plate observing system – Epos,).L'article de SRL présente notamment l'organisation de Résif-SI, les détails techniques de sa mise en œuvre et le catalogue des services fournis aux utilisateurs finaux