Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Overweight in Guadeloupe is a public health matter affecting children and adults. In the present study we evaluated the metabolic profile, including serum ghrelin, leptin and adiponectin levels, in normal weight, overweight and obese school children and we analyzed the potential changes in anthropometric and metabolic risk factors after a 1-year lifestyle intervention program. Methods: Parameters were assessed at baseline and at 1 year. Three groups (G) were defined according the International Obesity Task Force reference values, G1: normal weight / G2: overweight / G3: obese. The lifestyle intervention included dietary counseling, regular physical activity and family support. Results: A total of 120 children (G1: n = 44, G2: n = 39, G3: n = 37), aged 11– 15 years and 59 % girls were enrolled. Obese children showed significant lower HDL-C, adiponectin and ghrelin concentrations, higher triglycerides, fasting blood glucose, insulin and leptin levels and also higher frequencies of abdominal obesity (G1: 2.3 %, G2: 28.2 %, G3: 73 %) and insulin resistance (GI: 39 %, G2: 72 %, G3: 89 %) than the other groups. In the overall sample, the linear regressions exploring the associations of ghrelin, adiponectin and leptin with age, gender, BMI z-score, HOMA-IR and tanner stage as independent variables showed strong associations of leptin levels with weight status and insulin resistance at baseline. The models accounted for 58 % of variability in leptin levels compared with 26 and 15 % for adiponectin and ghrelin levels respectively. In 83 children who completed the program, significant decreases in BMI z-score in overweight and obese children were noted. Leptin levels decreased significantly only in the obese group whereas adiponectin concentrations increased significantly in the three groups, In obese children, a significant correlation was found between changes in BMI Z-score, and changes in leptin levels (r = 0.39; P = 0.049) but not with changes in adiponectin levels. Conclusions: Abdominal obesity and insulin resistance were highly prevalent in obese children highlighting their risk of metabolic complications in adulthood. A 1-year long lifestyle intervention was associated with improvement in BMI z-score and metabolic parameters.
ISSN: 1743-7075

Droits : http://creativecommons.org/licenses/by/
hal-01231394
http://hal.upmc.fr/hal-01231394
http://hal.upmc.fr/hal-01231394/document
http://hal.upmc.fr/hal-01231394/file/art_10.1186_s12986-015-0039-9.pdf
DOI : 10.1186/s12986-015-0039-9

Éditeur(s) : HAL CCSD
Résumé : Session "Posters"
National audience
Nous présentons une méthode permettant la mesure complète de la pose de la tête lors de captures vidéo monoculaires. Ce procédé utilise un modèle de visage et de texture précis. Le modèle facial, construit à partir d'une distribution de scans 3D haute résolution de visages, permet de générer des densités adaptées aux résolutions effectives. L'étape d'initialisation de la position du modèle est cruciale car elle conditionne le suivi ultérieur de la pose. Nous proposons ainsi d'utiliser une métrique composite construite sur des textures extraites de trois bases de données différentes. L'algorithme est alors capable de suivre le visage dans de vastes plages de poses avec une grande précision. Nous proposons des séquences vidéo de test dotées de vérité-terrain de pose précise et indépendante (précision de 0.1 degrés RMS)
Actes de la conférence RFIA 2012
Lyon, France

hal-00656565
https://hal.archives-ouvertes.fr/hal-00656565
https://hal.archives-ouvertes.fr/hal-00656565/document
https://hal.archives-ouvertes.fr/hal-00656565/file/rfia2012_submission_118.pdf

Éditeur(s) : HAL CCSD
Résumé : National audience
La sédimentation en baie du Mont Saint Michel se caractérise par la mixité des apports, presque exclusivement d’origine marine, carbonatés et silicoclastiques. La question du comblement de cet environnement hypertidal et de l’évolution de son trait de côte, représenté dans le fond de baie (sud et ouest) par des barrières coquillières, se pose à l’horizon des décennies à venir. Comment ce comblement va t-il être affecté par le changement climatique global marqué entre autres par l’accélération de la remontée du niveau marin et par des modifications potentielles de faunes (habitats, espèces..etc) auxquelles peut également contribuer le développement d’activités humaines comme la conchyliculture ?Les travaux présentés ici (projet Sédibaie, DDTM35 / Région Basse Normandie) ont pour objectif de quantifier le taux de sédimentation dans le fond de baie du Mont-Saint-Michel depuis les derniers siècles, et cela afin d’appréhender les tendances à venir. Pour ce faire des carottages courts (moy. 75 cm) ont été réalisés selon 5 radiales côte-large réparties de St Benoit des Ondes (près de Cancale) à La Chapelle Ste Anne (à l’Ouest du Mt St Michel). Les carottes ont fait l’objet d’analyses variées (faciès, granulométrie, teneur en carbonate, XRF, Scopix, datations 14C...). Un échantillonnage de surface a également été réalisé afin de caractériser les assemblages faunistiques actuels (malacofaune, microfaune, vivant, mort). Parallèlement, des travaux spécifiques sont menés sur les barrières coquillières (stratigraphie THR, évolution contenu faunistique, processus d’édification..). Les enregistrements étudiés sur les carottes couvrent la sédimentation du dernier millénaire au moins. Ils mettent en évidence le passage entre un environnement de dépôt dominé par l’action des marées, à un environnement de plus haute énergie, sans doute dominé par l’action des houles (tempêtes ?). Ce changement majeur, visible sur quasiment toutes les carottes à une profondeur variant entre 30 et 50 cm, s’opère peu après 1000 ans cal. BP. (à confirmer). Il est attribué à un changement climatique d’échelle au moins régionale (Atlantique nord). La complexite de l’enregistrement sédimentaire au-dessus du passage tidal/houle met en évidence une variabilité de faciès sédimentaires à haute fréquence, probablement liée à une fluctuation du climat de houle (NAO, Petit Age Glaciaire), ainsi que dans la partie supérieure à des changements d’apports bioclastiques relatifs au développement des installations conchylicoles.
25e Réunion des Sciences de la Terre
Caen, France

hal-01413154
https://hal.archives-ouvertes.fr/hal-01413154

Éditeur(s) : HAL CCSD
Résumé : International audience
Motivation: Data management and quality control of output from Illumina sequencers is a disk space- and time-consuming task. Thus, we developed Aozan to automatically handle data transfer, demultiplexing, conversion and quality control once a run has finished. This software greatly improves run data management and the monitoring of run statistics via automatic emails and HTML web reports. Availability and Implementation: Aozan is implemented in Java and Python, supported on Linux systems, and distributed under the GPLv3 License at: http://www.outils.genomique.biologie.ens.fr/aozan/. Aozan source code is available on GitHub: https://github.com/GenomicParisCentre/aozan.
Bioinformatics

hal-01545317
https://hal.archives-ouvertes.fr/hal-01545317
DOI : 10.1093/bioinformatics/btx154

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
ISSN: 1369-3786

hal-01118199
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118199
DOI : 10.3109/13693786.2010.511287
PUBMED : 21067335

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0031-0182

hal-00720714
https://hal.archives-ouvertes.fr/hal-00720714

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The temperate symbiotic sea anemone Anemonia viridis, a member of the Cnidaria phylum, is a relevant experimental model to investigate the molecular and cellular events involved in the preservation or in the rupture of the symbiosis between the animal cells and their symbiotic microalgae, commonly named zooxanthellae. In order to increase research tools for this model, we developed a primary culture from A. viridis animal cells. By adapting enzymatic dissociation protocols, we isolated animal host cells from a whole tentacle in regeneration state. Each plating resulted in a heterogeneous primary culture consisted of free zooxanthellae and many regular, small rounded and adherent cells (of 3-5 mu m diameter). Molecular analyses conducted on primary cultures, maintained for 2 weeks, confirmed a specific signature of A. viridis cells. Further serial dilutions and micromanipulation allowed us to obtain homogenous primary cultures of the small rounded cells, corresponding to A. viridis ``epithelial-like cells''. The maintenance and the propagation over a 4 weeks period of primary cells provide, for in vitro cnidarian studies, a preliminary step for further investigations on cnidarian cellular pathways notably in regard to symbiosis interactions.
ISSN: 0920-9069

hal-01546173
https://hal.archives-ouvertes.fr/hal-01546173
DOI : 10.1007/s10616-013-9566-2

Éditeur(s) : HAL CCSD John Libbey Eurotext
Résumé : International audience
Environmental health risk assessment is commonly used in France for risk management purposes. The Methodology section of the "Société française de santé environnement" (French Society for Environmental Health) seeks to improve the utility and implementation of risk assessment in France. An initial operational objective is to make a list of short-, intermediate- and long-term improvements. This inventory is based in part on the experience and expertise of society members in this area and in part on their analysis of "Science and Decisions: Advancing Risk Assessment" (National Research Council 2009). In this paper, the Society recommends modifications in the indications for and use of risk assessments, during each of the four stages of the process: hazard identification and dose-response assessment, exposure assessment, risk characterization, and results interpretation. Some may be implemented now, while others need consensus building or research because of gaps in knowledge. Environmental health risk assessment must be understood as a decision tool for risk management in situations of uncertainly. Thus, appropriate linkage is required between decision making and assessment, and between the methods and the expected results.
L'évaluation des risques sanitaires est fréquemment utilisée en France dans les processus de décision en santé environnementale. La section " Méthodologie d'évaluation des risques sanitaires " de la Société française de santé environnement (SFSE) s'est donnée pour objectif de proposer des éléments de réflexion et des outils méthodologiques en vue d'améliorer l'utilité et les pratiques de l'évaluation des risques sanitaires. Un premier objectif opérationnel est l'inventaire des améliorations possibles à court, moyen et long termes à apporter à la démarche et à son utilisation. Ce travail s'est fondé, d'une part, sur la pratique et l'expertise des membres de la section, et, d'autre part, sur une lecture critique du rapport " Science and Decisions : Advancing Risk Assessment " publié en 2009 par le National Research Council et portant également sur les évolutions de la démarche. Dans cet article, la section restitue les conclusions de cet inventaire critique et propose un certain nombre d'améliorations en termes d'indications et d'utilisations de l'évaluation des risques sanitaires pour chacune des quatre étapes : identification des dangers et relation dose-réponse ; évaluation de l'exposition ; caractérisation des risques ; et interprétation des résultats. Certaines recommandations peuvent être mises en oeuvre immédiatement ; d'autres, en préalable à leur mise en oeuvre, nécessitent un consensus ou encore de la recherche car les connaissances manquent. En conclusion, la section insiste sur le fait que l'évaluation des risques sanitaires doit être comprise comme une aide à la décision en situation d'incertitude ; l'articulation entre le contexte décisionnel et l'évaluation, sa méthodologie et les résultats attendus est donc primordiale.
ISSN: 1635-0421

ineris-00963325
https://hal-ineris.archives-ouvertes.fr/ineris-00963325
DOI : 10.1684/ers.2011.0435
INERIS : EN-2012-016

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A dense, local network of 30 geodetic markers covering a 50 × 60 km2 area in the southwestern European Alps (Briançon region) has been temporarily surveyed in 1996, 2006 and 2011 by GPS. The aim is to measure the current deformation in this seismically active area. The study zone is characterized by a majority of extensional and dextral focal mechanisms, along north–south to N160 oriented faults. The combined analysis of the three measurement campaigns over 15 years and up to 16 years of permanent GPS data from the French RENAG network now enables to assess horizontal velocities below 1 mm/year within the local network. The long observation interval and the redundancy of the dense campaign network measurement help to constrain a significant local deformation pattern in the Briançon region, yielding an average E–W extension of 16 ± 11 nanostrain/year. We compare the geodetic deformation field to the seismic deformation rate cumulated over 37 years, and obtain good coherencies both in amplitude and direction. Moreover, the horizontal deformation localized in the Briançon region represents a major part of the Adriatic-European relative plate motion. However, the average uplift of the network in an extensional setting needs the presence of buoyancy forces in addition to plate tectonics.
ISSN: 0264-3707

hal-01119724
https://hal.archives-ouvertes.fr/hal-01119724
DOI : 10.1016/j.jog.2015.02.001

Éditeur(s) : HAL CCSD
Résumé : International audience
Leishmania parasites induce an immunomodulation by subverting the host immune response towards a CD4(+) Th2 lymphocytic cell response that favors parasite persistence. Here, we report that after successful treatment of visceral leishmaniasis due to Leishmania infantum, an immune reconstitution syndrome revealing hip septic arthritis was associated with a switch from Th2 towards a Th1 cytokine profile, and a decrease in the level of immunomodulating factors, such as soluble HLA-G and indoleamine 2,3-dioxygenase (IDO) activity. We then measured IDO activity in a cohort of 39 patients and uninfected control subjects. Results showed significantly enhanced IDO activity in patients with visceral Leishmania infection, compared with uninfected control subjects (P < 0.001), but also compared with treated patients (P < 0.05). A decrease in IDO activity could constitute a relevant biomarker for the restoration of the immune response during visceral leishmaniasis.
Innate Immunity

inserm-00818884
http://www.hal.inserm.fr/inserm-00818884
DOI : 10.1177/1753425912473170
PUBMED : 23413147

Éditeur(s) : HAL CCSD American Association for the Advancement of Science
Résumé : International audience
Most eukaryotic organisms are arthropods. Yet, their diversity in rich terrestrial ecosystems is still unknown. Here we produce tangible estimates of the total species richness of arthropods in a tropical rainforest. Using a comprehensive range of structured protocols, we sampled the phylogenetic breadth of arthropod taxa from the soil to the forest canopy in the San Lorenzo forest, Panama. We collected 6144 arthropod species from 0.48 hectare and extrapolated total species richness to larger areas on the basis of competing models. The whole 6000-hectare forest reserve most likely sustains 25,000 arthropod species. Notably, just 1 hectare of rainforest yields >60% of the arthropod biodiversity held in the wider landscape. Models based on plant diversity fitted the accumulated species richness of both herbivore and nonherbivore taxa exceptionally well. This lends credence to global estimates of arthropod biodiversity developed from plant models.
ISSN: 0036-8075

hal-00817285
https://hal.archives-ouvertes.fr/hal-00817285
https://hal.archives-ouvertes.fr/hal-00817285/document
https://hal.archives-ouvertes.fr/hal-00817285/file/1226727Revisedtext.pdf
DOI : 10.1126/science.1226727

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Understanding long-term variability in the frequency of intense storm activity is important for assessing whether changes are controlled by climate evolution. Understanding this variability is also important for predicting present and future community vulnerability and economic loss. Our ability to make these assessments has been limited by the short (less than 50 years) instrument record of storm activity. Storm-induced deposits preserved in the sediments of coastal lagoons offer the opportunity to study the links between climatic conditions and storm activity on longer timescales. In this study, we present a record of these extreme climatic events that have occurred in the French Mediterrannean coast over the past 1500 years. The identification of these extreme events is based on the analysis of sediment cores from Gulf of Aigues-Mortes lagoons that contain a specific sedimentary and geochemical signature associated with intense storms.;Overwash deposits do not show any evidence of intense storm landfalls in the region for several hundred years prior to the late 17th century A.D. The apparent increase in intense storms around 250 years ago occurs during the latter half of the Little Ice Age, a time of lower continental surface temperatures. Comparison of the sediment record with palaeoclimate records indicates that this variability was probably modulated by atmospheric dynamics. The apparent increase of the superstorm activity during the latter half of the Little Ice Age was probably due to the thermal gradient increase leading to enhanced lower tropospheric baroclinicity over a large Central Atlantic/European domain and leading to a modification of the occurrence of extreme wind events along the French Mediterranean coast. A complete understanding of the relationship between climate fluctuations, storm activity, and the coastal response will be crucial to predicting the impacts of future climate change.
ISSN: 0031-0182

hal-00617525
https://hal.archives-ouvertes.fr/hal-00617525
DOI : 10.1016/j.palaeo.2010.11.009

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : Three new monoterpene indole alkaloids (13) have been isolated from the bark of Geissospermum laeve-, together with the known alkaloids (-)-leuconolam (4), geissolosimine (5), and geissospermine (6). The structures of 1-3 were elucidated by analysis of their HRMS and NMR spectroscopic data. The absolute configuration of geissolaevine (I). was deduced from the comparison of experimental and theoretically calculated ECD spectra. The isolation workflow was guided by a molecular networking-based dereplication strategy using an in-house database of monoterpene indole alkaloids. In addition, five known compounds previously undescribed in the Geissospermum genus were dereplicated from the G. laeve alkaloid extract network and were assigned with various levels of identification confidence. The antiparasitic activities against Plasmodium falciparum and Leishmania donovani as well as the Ortotoxic activity against the MRC-5 cell line were determined for compounds 1-5.
ISSN: 0163-3864

hal-01605065
https://hal.archives-ouvertes.fr/hal-01605065
DOI : 10.1021/acs.jnatprod.6b01013
PRODINRA : 402605
PUBMED : 28282127

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Diamond-bearing UHP metamorphic rocks witness for subduction of lithospheric slabs into the mantle and their return to shallow levels. In this study we present U–Pb and trace elements analyses of zircon and rutile inclusions from a diamond-bearing garnet megacryst collected in a mélange unit exposed on the northern margin of Africa (Edough Massif, NE Algeria). Large rutile crystals (up to 300 μm in size) analyzed in situ provide a U–Pb age of interpreted as dating the prograde to peak subduction stage of the mafic protolith. Trace element analyses of minute zircons (≤30 μm) indicate that they formed in equilibrium with the garnet megacryst at a temperature of 740–810 °C, most likely during HP retrograde metamorphism. U–Pb analyses provide a significantly younger age of attributed to exhumation of the UHP units. This study allows bracketing the age of UHP metamorphism in the Western Mediterranean Orogen to the Oligocene/early Miocene, thus unambiguously relating UHP metamorphism to the Alpine history. Exhumation of these UHP units is coeval with the counterclockwise rotation of the Corsica–Sardinia block and most likely resulted from subduction rollback that was driven by slab pull.
ISSN: 0012-821X

hal-01622789
https://hal.archives-ouvertes.fr/hal-01622789
DOI : 10.1016/j.epsl.2017.06.043

Éditeur(s) : HAL CCSD Centre National de la Recherche Scientifique
Résumé : Avec l'augmentation récente de la population mondiale et des infrastructures en domaine littoral, les tempêtes et les cyclones sont devenus un des risques majeurs à l'échelle globale. La Méditerranée, et plus particulièrement le Golfe du Lion, ne sont pas épargnés par ces phénomènes. La tempête de 1982 par exemple, de catégorie 2 sur l'échelle de Saffir-Simpson est responsable du décès de quinze personnes et de plus de 400 millions d'euros de pertes économiques. La prévision de ces événements à partir de modèles climatiques est devenue primordiale. Le problème majeur dans cette approche est le manque de recul dans le temps pour calibrer ces modèles. Notre approche a donc été de reconstituer ces tempêtes du passé à partir de l'étude d'archives sédimentaires (paléotempestologie). Les lagunes du littoral languedocien sont les réceptacles de matériels terrigènes provenant des bassins versants en période de crues, mais aussi de sables transportés par la mer en période de tempêtes. L'étude des archives sédimentaires dans l'étang de Pierre Blanche nous a permis d'identifier et de reconstituer l'alternance des événements les plus extrêmes au cours des 2000 dernières années. La fréquence de ces tempêtes semble varier dans le temps et une augmentation significative est constatée durant la fin du Petit Âge Glaciaire.
ISSN: 1142-2904

hal-00486349
https://hal.archives-ouvertes.fr/hal-00486349

Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here we report that serum levels of CD95L are higher in TNBC patients compared to other breast cancer patients. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility, due to formation of an unconventional CD95-containing receptosome termed the motility-inducing signaling complex. Formation of this complex was instrumental for Nox3-driven ROS generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a pro-metastatic function for metalloprotease-cleaved CD95L in triple-negative breast cancers, revisiting its role in carcinogenesis.
ISSN: 0008-5472

hal-00873634
https://hal.archives-ouvertes.fr/hal-00873634
PUBMED : 24072745
DOI : 10.1158/0008-5472.CAN-13-1794

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Seabirds concentrate nutrients from large marine areas on their nesting islands playing an important ecological role in nutrient transfer between marine and terrestrial ecosystems. Here we investigate the role of guano on corals reefs across scales by analyzing the stable nitrogen isotopic (delta N-15) values of the scleractinian coral Pocillopora damicornis on fringing reefs around two Pacific remote islets with large seabird colonies. Marine stations closest to the seabird colonies had higher nitrate + nitrite concentrations compared to more distant stations. Coral and zooxanthellae delta N-15 values were also higher at these sites, suggesting that guano-derived nitrogen is assimilated into corals and contributes to their nitrogen requirements. The spatial extent of guano influence was however restricted to a local scale. Our results demonstrate that seabird-derived nutrients not only spread across the terrestrial ecosystem, but also affect components of the adjacent marine ecosystem. Further studies are now needed to assess if this nutrient input has a positive or negative effect for corals. Such studies on remote islets also open fresh perspectives to understand how nutrients affect coral reefs isolated from other anthropogenic stressors.
ISSN: 2045-2322

hal-01681575
https://hal.archives-ouvertes.fr/hal-01681575
DOI : 10.1038/s41598-017-03781-y

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Histoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved in this French overseas territory which offers an interesting model of Amazonian pathogen ecology. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana. METHODS: A retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated Histoplasma capsulatum var. capsulatum histoplasmosis admitted in one of the three main hospitals in French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods. RESULTS: There were 124 deaths (45.3%) and 46 early deaths (16.8%) among 274 patients. Three time periods of particular interest were identified: 1992-1997, 1998-2004 and 2005-2011. The two main temporal trends were: the proportion of early deaths among annual incident histoplasmosis cases significantly declined four fold (χ2, p<0.0001) and the number of annual incident histoplasmosis cases increased three fold between 1992-1997 and 1998-2004, and subsequently stabilized. CONCLUSION: From an occasional exotic diagnosis, AIDS-related histoplasmosis became the top AIDS-defining event in French Guiana. This was accompanied by a spectacular decrease of early mortality related to histoplasmosis, consistent with North American reference center mortality rates. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease.
ISSN: 1935-2727

inserm-01065109
http://www.hal.inserm.fr/inserm-01065109
http://www.hal.inserm.fr/inserm-01065109/document
http://www.hal.inserm.fr/inserm-01065109/file/PLOS_Neglected_Tropical_Dis_2014.pdf
http://www.hal.inserm.fr/inserm-01065109/file/2014_Adenis_-_HIV-associated_histoplasmosis_early_mor.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥ 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥ 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥ 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.
ISSN: 0924-8579

hal-00875083
https://hal.archives-ouvertes.fr/hal-00875083
DOI : 10.1016/j.ijantimicag.2013.02.016
PUBMED : 23562640

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
ISSN: 0001-6322

hal-00875723
https://hal.archives-ouvertes.fr/hal-00875723
DOI : 10.1007/s00401-013-1084-y
PUBMED : 23400299