Hypoxia-inducible factor (HIF1α) gene expression in human shock states.

International audienceABSTRACT: INTRODUCTION: Hypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1α as a prognosis marker in patients suffering from shock. METHODS: Fifty consecutive adult patients with shock and 11 healthy volunteers were prospectively enrolled in the study. RNA was extracted from whole blood samples and expression of HIF1α was assessed over the first four hours of shock. The primary objective was to assess HIF1α as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1α as a diagnostic and follow-up marker. Patient survival was evaluated at day 28. RESULTS: The causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). HIF1α expression was significantly higher in the shock patients than in the healthy volunteers (121 (range: 72-168) versus 48 (range: 38-54) normalized copies, P <0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 (range 84-183) versus 121(range 72-185) normalized copies, P = 0.92), and did not significantly change within the study period. CONCLUSIONS: The present study is the first to demonstrate an increased expression of HIF1α in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome.

International audienceBACKGROUND: Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. DESIGN AND METHODS: One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20 × 10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. RESULTS: Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. CONCLUSIONS Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making

Fréquence des contacts des Franciliens de 50-70 ans avec leurs parents

Au moment où la canicule a révélé la solitude de certaines personnes âgées, l'enquête « Biographies et entourage » permet d'étudier les relations qu'entretiennent les Franciliens de 50 à 70 ans avec leurs parents. Ces relations semblent être majoritairement entretenues par les femmes

Origine géographique des Franciliens âgés de 50 à 70 ans

Quatre Franciliens sur dix,âgés de 50 à 70 ans, sont nés en Île-de-France. Les autres sont nés en province ou à l’étranger. Force est de constater que l’Île-de-France s’est affirmée comme région d’accueil et pôle de travail pour ces générations. «Biographies et entourage» retrace la trajectoire résidentielle de 2 830 Franciliens nés entre 1930 et 1950 pour étudier leurs origines, mais aussi celles de leurs parents et de leurs grands-parents

La famille dans tous ses états ?: Cinquante questions... pour les cinquante ans à venir ?

http://www.iau-idf.fr/fileadmin/Etudes/etude_843/Cahier_n__158.pdfNational audienceEntretien avec Maurice Godelier. Avec la contraception, les unions libres, le divorce par consentement mutuel, la libéralisation des mœurs conduit à la dissociation du conjugal et du parental. Et la science ouvre, par ailleurs, de nouvelles possibilités de procréation. Ces transformations sont-elles porteuses de risques pour les enfants et le lien social

OLES Online Laboratory for Environmental Sciences

International audienceThe integrated cyber-infrastructure, OLES, provides an access to observation data and to tools and models built to enhance our understanding on the evolution of the Earth's water resources and climate. OLES aims at i) extracting the required data from database portals using OGC webservice (CSW, SOS), ii) building a specific process chain based on modules that use NetCDF format for exchanging data, iii) running the process in chosen computing facilities, OLES can connect outside on a private LAN and iv) visualizing the result of the process. Based on J2EE, the MMI of OLES is a web interface and interacts with EJB objects. OLES uses web services to communicate with a sequencer developed in C++

MobRISK: a model for assessing the exposure of road users to flash flood events

International audienceRecent flash flood impact studies highlight that road networks are often disrupted due to adverse weather and flash flood events. Road users are thus particularly exposed to road flooding during their daily mobility. Previous exposure studies, however, do not take into consideration population mobility. Recent advances in transportation research provide an appropriate framework for simulating individual travel-activity patterns using an activity-based approach. These activity-based mobility models enable the prediction of the sequence of activities performed by individuals and locating them with a high spatial-temporal resolution. This paper describes the development of the MobRISK microsimulation system: a model for assessing the exposure of road users to extreme hydrometeorological events. MobRISK aims at providing an accurate spatiotemporal exposure assessment by integrating travel-activity behaviors and mobility adaptation with respect to weather disruptions. The model is applied in a flash-flood-prone area in southern France to assess motorists' exposure to the September 2002 flash flood event. The results show that risk of flooding mainly occurs in principal road links with considerable traffic load. However , a lag time between the timing of the road submersion and persons crossing these roads contributes to reducing the potential vehicle-related fatal accidents. It is also found that sociodemographic variables have a significant effect on individual exposure. Thus, the proposed model demonstrates the benefits of considering spatiotemporal dynamics of population exposure to flash floods and presents an important improvement in exposure assessment methods. Such improved characterization of road user exposures can present valuable information for flood risk management services

1H, 13C and 15N resonance assignment of the N-terminal domain of PilB from Neisseria meningitidis

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Solution structure and dynamics of the reduced and oxidized forms of the N-terminal domain of PilB from Neisseria meningitidis.

International audienceThe secreted form of the PilB protein was proposed to be involved in pathogen survival fighting against the defensive host's oxidative burst. PilB protein is composed of three domains. The central and the C-terminal domains display methionine sulfoxide reductase A and B activities, respectively. The N-terminal domain, which possesses a CXXC motif, was recently shown to regenerate in vitro the reduced forms of the methionine sulfoxide reductase domains of PilB from their oxidized forms, as does the thioredoxin 1 from E. coli, via a disulfide bond exchange. The thioredoxin-like N-terminal domain belongs to the cytochrome maturation protein structural family, but it possesses a unique additional segment (99)FLHE (102) localized in a loop. This segment covers one edge of the active site in the crystal structure of the reduced form of the N-terminal domain of PilB. We have determined the solution structure and the dynamics of the N-terminal domain from Neisseria meningitidis, in its reduced and oxidized forms. The FLHE loop adopts, in both redox states, a well-defined conformation. Subtle conformational and dynamic changes upon oxidation are highlighted around the active site, as well as in the FLHE loop. The functional consequences of the cytochrome maturation protein topology and those of the presence of FLHE loop are discussed in relation to the enzymatic properties of the N-terminal domain