Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Humans may be exposed via their environment to multiple chemicals as a consequence of human activities and use of synthetic products. Little knowledge is routinely generated on the hazards of these chemical mixtures. The metabolomic approach is widely used to identify metabolic pathways modified by diseases, drugs, or exposures to toxicants. This review, based on the state of the art of the current applications of metabolomics in environmental health, attempts to determine whether metabolomics might constitute an original approach to the study of associations between multiple, low-dose environmental exposures in humans. Studying the biochemical consequences of complex environmental exposures is a challenge demanding the development of careful experimental and epidemiological designs, in order to take into account possible confounders associated with the high level of interindividual variability induced by different lifestyles. The choices of populations studied, sampling and storage procedures, statistical tools used, and system biology need to be considered. Suggestions for improved experimental and epidemiological designs are described. Evidence indicates that metabolomics may be a powerful tool in environmental health in the identification of both complex exposure biomarkers directly in human populations and modified metabolic pathways, in an attempt to improve understanding the underlying environmental causes of diseases. Nevertheless, the validity of biomarkers and relevancy of animal-to-human extrapolation remain key challenges that need to be properly explored.
ISSN: 1093-7404

hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/file/Potential_input_from_metabolomics_accepted.pdf
DOI : 10.1080/10937404.2013.860318

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Objective: To describe characteristics and outcomes of HIV-infected patients with Pneumocystis jirovecii pneumonia (PCP) over 2004–2011 in France, in particular in those previously enrolled (PE) in the French Hospital Database on HIV (FHDH). Methods: PE patients with an incident PCP were compared with patients with an inaugural PCP revealing HIV infection (reference). Adequate adherence to care was defined as a CD4 measurement at least every 6 months. Immune reconstitution (CD4$200/mm 3) and risk of death were studied using Kaplan-Meier estimates and multivariable Cox proportional hazards models. Results: In a context of a decreasing incidence of PCP, 1259 HIV-infected patients had a PCP diagnosis, and 593 (47%) were PE patients of whom 161 (27%) have had a prior history of AIDS-defining clinical illness (prior ADI). Median time since enrolment was 8 years for PE patients; 74% had received cART. Median proportion of time with adequate adherence to care was 85% (IQR, 66–96) for all FHDH enrollees, but only 45% (IQR, 1–81) for PE patients during the 2 years before PCP. Median CD4 cell count (38/mm 3) and HIV viral load (5.2 log10 copies/ml) at PCP diagnosis did not differ between PE patients and the reference group. Three year mortality rate of 25% was observed for PE prior ADI group, higher than in PE non-prior ADI group (8%) and the reference group (9%) (p,0.0001). In the PE prior ADI group, poor prognosis remained even after adjustment for virological control and immune reconstitution (HR, 2.4 [95%CI, 1.5–3.7]). Conclusion: Almost 50% of PCP diagnoses in HIV-infected patients occurred presently in patients already in care, mainly with a previous cART prescription but with waning adherence to care. Having repeated ADI is contributing to the risk of death beyond its impact on immune reconstitution and viral suppression: special efforts must be undertaken to maintain those patients in care.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01345090
http://hal.upmc.fr/hal-01345090
http://hal.upmc.fr/hal-01345090/document
http://hal.upmc.fr/hal-01345090/file/journal.pone.0094183.PDF
DOI : 10.1371/journal.pone.0094183

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. METHODS: We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. RESULTS: Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. CONCLUSION: TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis.
ISSN: 1462-0324

hal-01155105
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01155105
DOI : 10.1093/rheumatology/kev129
PUBMED : 26001634

Éditeur(s) : HAL CCSD
Résumé : In the bay of Aigues-Mortes, the managers of the co astal cities try to preserve the socio-economic and patrimonial stakes against the coastal hazards, such as contamination, storm surge and erosion. In this context, a massive beach nourishment of sand (1 million of m3 for 10km of coastline) was made at the beginning of year 2008 to reduce erosion. The REPBAM project (REchargements et Panaches sédiment aires dans la Baie d'Aigues-Mortes) aims to qualify and quantify by in-situ measurements and numerical modelling: 1. the geomorphological evolution of this modified coast and 2. the impact of the sediment's resuspension on the coastal ecosystems, in particular the one of the Posidonia oceanica seagrass. A numerical modelling "wave/current/sediment" is first implemented for December 2008. Nested and curvilinear grids allow a very high resolution for the beach area but also include the inner shelf where the seagrasses are located. Hydrodynamic and topo-bathymetric measurements were acquired from January to May 2012. Model and measurements results show the same trends during storms: strong currents, seaward migrationof the innerbar, sediment resuspension and turbid on the inner shelf.
Coastal Dynamics 2013
Arcachon, France

hal-00908082
https://hal.archives-ouvertes.fr/hal-00908082

Éditeur(s) : HAL CCSD Geological Society of America
Résumé : International audience
How convergent systems distribute strain among frontal thrusts is a major concern regarding seismic hazard assessment. Along the 2500 km Himalayan arc, the seismic behavior of the Bhutan region is unknown, because it corresponds to the only portion of the arc where no evidence of major earthquakes has been reported. This can be due either to the fact that no active tectonic studies have been conducted or to continental shortening being absorbed by the Shillong plateau 150 km farther south. Analyzing offset fluvial terraces in south-central Bhutan shows that two major earthquakes ruptured the Himalayan frontal thrust during the last millennium, and that a comparable rate of Holocene deformation (∼20 mm/yr) is accommodated across the Himalaya in Bhutan as in central Nepal. Thus, the propensity for great earthquakes in Bhutan is similar to what is observed in neighboring portions of the Himalaya arc. This in turn suggests that the shortening process beneath the Shillong plateau has little effect on how strain accumulates within the Bhutanese Himalaya.
ISSN: 0091-7613

hal-01122799
https://hal.archives-ouvertes.fr/hal-01122799
DOI : 10.1130/G35162.1

Résumé : Les pathologies inflammatoires démyélinisantes primitives du système nerveux central (SNC) sont dominées par deux entités : la sclérose en plaques (SEP) et la neuromyélite optique (NMO). Ces deux pathologies se différencient par : 1. leur phénotype, la NMO se caractérisant par une myélite extensive dans le plan transversal et longitudinal et peu de lésions encéphaliques initiales ; 2. leur sévérité, le pronostic de la NMO étant moins bon que celui de la SEP ; 3. leur mécanisme immunologique, puisque l’immunité humorale domine nettement dans la NMO, cette pathologie répondant peu ou pas aux traitementshabituellement prescrits dans la SEP. Un anticorps sérique (IgG-NMO) a été retrouvé chez les patients atteints de NMO avec une sensibilité de 50-70% et une spécificité de 90-100%. Cet anticorps a pour cible le principal canal hydrique du SNC, l’aquaporine-4 (AQP4), qui se situe principalement sur les pieds astrocytaires jalonnant la barrière hémato-encéphalique. La SEP est relativement familière des neurologues car décrite sur le plan épidémiologique et dans son histoire naturelle depuis plus d’un siècle à travers de larges séries réalisées parfois en population générale. Son approche thérapeutique progresse suite à des essais contrôlés qui s’accumulent depuis maintenant près de 20 ans. Toutefois, la majorité des travaux ont été effectués chez les populations Caucasiennes en raison de sa plus grande fréquence dans ces populations. A l’inverse, la NMO garde encore un relatif mystère à cause de sa relative rareté, l’établissement très récent de critères diagnostiques et une physiopathologie très récemment éclaircie par la découverte de l’IgG-NMO qui a indiscutablement suscité un regain d’intérêt de cette affection. Ainsi, son incidence est quasiment inconnue de même que sa susceptibilité génétique. La progression du handicap de la NMO qu’il soit visuel ou moteur à l’évidence sévère, ne repose toujours pas sur des chiffres précis, la description des lésions neuroradiologiques reste encore très embryonnaire. Enfin, même s’il existe un consensus pour traiter énergiquement les poussées de NMO et les espacer, il n’existe quasiment aucune étude prospective.
Introduction: Aim of the study is to describe épidemiology, phenotype and treatment of demyelinating inflammatory diseases of the central nervous system (CNS) namely multiple sclerosis (MS) and neuromyelitis optica (NMO) in French West Indies.Epidemiology: MS emerged in the French West Indian (FWI) population with an incidence of 1.27/100 000 (CI 95%: 1.16-1.38) for the period 1992-2007 while incidence of NMO remained stable at 0.19/100,000 (CI 95%: 0.15–0.23). Both migration in Metropolitean France (MF) and decrease of sun exposure were risk factors for MS acquisition in FWI. Phenotype and treatment of NMO: NMO is a very rapidly disabling disease with median times to reach DSS 3, 6 and 8 of one year, 8 years and 22 years respectively. However, treatment by plasma exchanges were shown to reduce sequellae of NMO attacks ; mitoxantrone and rituximab reduced significantly annualized relapse rate (ARR) from 1.7 to 0.29 (p<10-4) and from 1,34 to 0,56 (p=0.0005) respectively, improving dramatically natural course of NMO.Phenotype and treatment of MS: Absence of Migration in MF in MS patients was found to be the strongest independent predictive factor of disability progression to DSS 6 (hazard ratio, 2.59; p=0.0002); beside short time to DSS3 (p=0.005), later age at onset (p=0.005), and multi-symptomatic onset (p=0.03). Treatment of MS by interferon beta-1 had a moderate impact in MS while natalizimab proved to be highly effective by reducing drastically ARR and inflammatory parameters on magnetic resonance imaging. Conclusion: Spectrum of demyelinating inflammatory disorders of CNS has reversed in French West Indies with overrepresentation of MS. Agressive therapy is needed to improve prognosis of NMO. Rapidly increasing of its incidence makes MS a new public health problem in French West Indies.

http://www.theses.fr/2012AGUY0511/document

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life. OBJECTIVES: Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals. METHODS: We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures. RESULTS: We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight. CONCLUSIONS: Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. https://doi.org/10.1289/EHP1014.
Environmental Health Perspectives

hal-01579609
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579609
DOI : 10.1289/EHP1014
PUBMED : 28796631

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Northwest Iran is characterized by a high level of historical and instrumental seismicity related to the ongoing convergence between the Arabian and Eurasian plates. In this region, the main right-lateral strike-slip fault known as the North Tabriz fault (NTF) forms the central portion of a large crustal fault system called the Tabriz fault system (TFS). The NTF is a major seismic source along which at least three strong and destructive earthquakes have occurred since 858 AD. The two most recent destructive seismic events occurred in 1721 AD and 1780 AD, rupturing the SE and NW fault segments, respectively. This paper reports paleoseismological and quantitative geomorphologic investigations on the SE segment of the NTF, between the cities of Bostanabad and Tabriz. These observations help to improve our understanding of the seismic hazard for Tabriz city and its surrounding areas. Our field investigations revealed evidence of successive faulting events since the Late Quaternary. Paleoseismic investigations indicate that since 33.5 kyr, the SE segment of the NTF has experienced at least three major (M>7.5) seismic events, including the 1721 AD earthquake (M=7.6–7.7). Along the NW segment of the fault, however, our results suggest that the amount of strong (M~7.5) seismic events during the same period is significantly greater than along the SE segment. One possible explanation of such a difference in seismic activity is that the Late Quaternary-Holocene coseismic slip rate is decreasing along the NTF from the northwest to the southeast. This explanation contradicts the former hypothesis of a constant slip rate along the whole length of the NTF. In addition, more distributed deformation along several parallel fault branches, in a wider fault zone of the SE segment of the NTF may be considered as additional evidence for the estimation of lower rate of deformation along the fault segment. Such a slip distribution pattern can explain the existence of smaller (~300 m) Pliocene-Quaternary cumulative dextral offsets along the SE fault segment than the measured cumulative offsets along the NW segment (~800 m) of the NTF.
ISSN: 0040-1951

hal-01089420
http://hal.upmc.fr/hal-01089420
http://hal.upmc.fr/hal-01089420/document
http://hal.upmc.fr/hal-01089420/file/Solaymani%20Azad%20et%20al.%2C%202014%20%28accepted%29.pdf
DOI : 10.1016/j.tecto.2014.11.010