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Inertial confinement fusion experiments on large laser facilities such as the LMJ in Bordeaux or the NIF in the United States, involve the propagation of lasers through large plasmas (several millimeters). A large number of instabilities called wave coupling are likely to appear, and scatter the light in a different direction from the incident electromagnetic wave. In particular, Raman and Brillouin backscattering, as well as energy exchange between laser beams result from these wave couplings. Techniques called optical smoothing are used in large facilities to try to reduce these phenomena. The beams, once smoothed, are composed of many micrometric hot spots called speckles. During these experiments, the beams, focused around a target, are going to cross each other. The coupling of two coherent electromagnetic waves in a non-linear medium (the plasma), can induce an energy exchange between the two beams. The crossing of the lasers creates an interference grating, where the ponderomotive force expels the electrons. The ions follow the electrons due to the electrostatic spring force, generating a density modulation, or acoustic wave, which diffracts the electromagnetic waves from one beam to the other. This exchange, called Cross-beam Energy Transfer (CBET) takes place if the lasers have slightly different frequencies, or if the latter are equal but the plasma is moving in the direction of the acoustic wave. We have shown that, although these two situations are often considered equivalent in hydrodynamic models, they are in fact different. This is due to the fact that the exchange is commonly calculated by considering the laser beams as plane waves, i.e. neglecting the laser smoothing. In order to demonstrate this non-equivalence, we first studied an academic situation, considering the crossing of two laser beams each constituted of 4 Gaussian speckles. Different simulations have been performed with a particle-in-cell kinetic code, solving the Vlasov and Maxwell equations. The simulations showed that when the interaction is induced by a moving plasma, plane wave models are able to predict the exchange between the Gaussian beams. By contrast, when the exchange is induced by different laser frequencies, plane wave models overestimate the energy transfer. Moreover, we were able to distinguish two different configurations for the case where the laser frequencies are different. In the first case, the acoustic waves from different speckle crossings are in phase, and a constructive interference results from their interaction. In the other case, the waves are out of phase resulting in a destructive interference. It has been shown that although the exchange is greater in the in-phase case, the exchange remains lower than in the plasma flow case. The phase shift is therefore not the only source of difference between the two situations in which CBET appears. These results were obtained by considering a weakly Landau-damped plasma, i.e. a situation where the acoustic wave propagates and may encounter several speckle crossings before being damped. In a second step, a more realistic modeling of the smoothed beams has been adopted. For this purpose, the fields of a smoothed laser beam have been computed in an exact way, allowing to perform more accurate simulations and to build a model taking into account the real structure of the speckles. The previous results concerning the non-equivalence between the plasma flow and wavelength shift cases have been confirmed, even in the case of a strongly Landau-damped plasma. We were then able to show that the resonance conditions allowing the energy transfer to take place are also affected by the laser smoothing. In particular, the resonance width is broadened by the spatial smoothing.; Les expériences de fusion par confinement inertiel sur les grandes installations laser, telles que le LMJ à Bordeaux ou le NIF aux États-Unis, nécessitent la propagation des lasers à travers des plasmas de grandes tailles (plusieurs millimètres). Un grand nombre d'instabilités dites de couplages d'ondes peuvent apparaître, et diffusent la lumière dans une direction différente de l'onde électromagnétique incidente. En particulier, les diffusions arrières Raman et Brillouin, ainsi que l'échange d'énergie entre faisceaux laser en résultent. Des techniques dites de lissage optique sont utilisées pour tenter de réduire ces phénomènes. Les faisceaux, une fois lissés, sont constitués de nombreux points chauds micrométriques nommés speckles. Lors de ces expériences, les faisceaux, focalisés autour d'une cible, vont être amenés à se croiser.Le couplage de deux ondes électromagnétiques cohérentes dans un milieu non-linéaire (le plasma), peut induire un échange d'énergie entre les faisceaux. Le croisement des lasers crée un réseau d'interférences, où la force pondéromotrice expulse les électrons. Les ions suivent les électrons à cause de la force de rappel électrostatique. Cela crée une modulation de densité, ou onde acoustique, qui diffracte les ondes électromagnétiques d'un faisceau vers l'autre. Cet échange, nommé Cross-beam Energy Transfer (CBET) a lieu si les lasers ont des fréquences différentes, ou si ces dernières sont égales mais que le plasma est en mouvement dans la direction de l'onde acoustique. Nous avons montré que, bien que ces deux situations soient souvent considérées comme équivalentes dans les modèles hydrodynamiques, elles sont en réalité différentes. Ceci est dû au fait que l'échange est communément calculé en considérant les faisceaux laser comme des ondes planes, c'est-à-dire en négligeant le lissage laser. Afin de démontrer cette non-équivalence, nous avons, dans un premier temps, étudié une situation académique, en considérant le croisement de deux faisceaux lasers constitués chacun de 4 speckles Gaussiens. Différentes simulations ont été effectuées grâce à un code cinétique "particle-in-cell", résolvant les équations de Vlasov et de Maxwell. Les simulations ont montré que lorsque l'interaction est induite par un plasma en mouvement, les modèles du type onde plane sont en mesure de prédire l'échange entre les faisceaux Gaussiens. Au contraire, lorsque l'échange est induit par des fréquences laser différentes, ces modèles surestiment le transfert d'énergie. Nous avons aussi mis en évidence deux configurations distinctes dans le cas où les fréquences laser sont différentes. Dans la première situation, les ondes acoustiques issues de différents croisements de speckles sont en phase, et une interférence constructive résulte de leur interaction. Dans l'autre situation, les ondes sont déphasées ce qui donne une interférence destructive. Nous avons montré que, bien que l'échange soit plus important dans la situation en phase, il demeure inférieur au cas flot de plasma. Le déphasage n'est donc pas la seule cause de la différence entre une interaction avec ou sans flot. Nos résultats ont été obtenus en considérant un plasma faiblement amorti, où l'onde acoustique se propage et peut rencontrer plusieurs croisements de speckles avant que son amplitude n'ait significativement décru. Dans un second temps, nous avons considéré une situation plus proche de celle d'un croisement de faisceaux lissés. Nous avons calculé exactement le champ d'un faisceau laser lissé, ce qui a permis d'effectuer des simulations plus précises et de construire un modèle tenant compte de la structure réelle des speckles. Les résultats précédents ont été confirmés, même dans le cas d'un plasma fortement amorti. Nous avons également pu montrer que les conditions de résonance permettant au transfert d'énergie d'avoir lieu sont elles aussi affectées par le lissage laser. En particulier, le lissage spatial augmente la largeur de résonance.

International audience; Background: It has been proven that vaccination is effective against Human Papillomavirus (HPV) infections, genital warts, and pre-cancerous and cancerous cervical lesions. Nevertheless, the HPV vaccine coverage of 37.4% in 2021 in France is one of the lowest in Europe. To explore and understand the reason why French population is so late compared to its neighbours, we carried out focus groups with mothers and with National Education school staff. We aimed to identify knowledge and perceptions of HPV in both study populations, as well as factors influencing HPV vaccination.Methods: Between January 2020 and March 2021, we performed a qualitative study using an inductive approach with a thematic content analysis (TCA). We conducted semi-structured focus groups with 29 people including 15 mothers of adolescents in middle schools and 14 school staff from the national education system.Results: Different factors influenced the decision-making process of parents and school staff: knowledge and perceptions of HPV and its vaccine, sources of information about HPV and vaccination. Mothers' discourses differed from those of school staff. They mentioned the importance of gynaecological monitoring and the negative image of pharmaceutical companies, and questioned internet as a reliable source of information. For their part, school staff mentioned cultural and/or religious affiliation, municipalities’ role to inform the population, and ethical dilemma or logistical challenges regarding HPV vaccination in schools.Conclusion: The results of these focus groups provided information on which elements may harm or help HPV vaccination. Identified perceptions, beliefs, knowledge, barriers, and facilitators will help us to build an intervention program focus on general practitioners (GP), school staff, parents, and adolescents.

International audience; The Climate Graduate School of the Institut Pierre-Simon Laplace (CGS-IPSL) iscurrently developing a series of seven courses online for Master students. On these sevencourses of 3 ECTS each, three have a strong focus on the ocean: Dynamics of the Ocean andAtmosphere; Contemporary Biogeochemical Cycles; Study of Paleo-climates. Each course is ledby a pair of university teachers specialists in their field accompanied by a pedagogical andgraphic team in order to design all resources specifically adapted to graduate students andonline education. Indeed, our first goal is to open these courses as self-paced learning underthe IPSL Learning Management System (Moodle) to students who will be joining CGS-IPSLmasters without having all the prerequisites so that they can update their academicbackground. These courses could also be open to second year CGS IPSL Master students whoaimed at acquiring credits on a secondary theme not necessarily developed in their master (e.g.on biogeochemistry for students registered in an ocean – climate master). Finally all the e-resources developed will be made available at least to the educational community of the CGS-IPSL that include several Universities in and around Paris (Sorbonne Universite, Paris Saclay,Universite Versailles Saint Quentin, Université Paris Est Créteil...) in order to reuse theseresources for higher education either on-line or face-to-face courses. The courses will beavailable in both French and English so that international students can have access to these e-resources.

Background: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients’ characteristics in the Greek national IPF cohort with suspected heritability. Patients and Methods: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. Results: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. Conclusion: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease’s genetic “richesse,” complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating “personalized” medical care driven by genotypes in the near future.

Climate warming and evolution water demand for anthropogenic activities are two related ongoing changes that may increase existing pressure on water resources. Adaptation strategies are usually thought on the basis of hydrological projections. These projections, however, rarely incorporate changes in water and land management, issues that are then addressed by the adaptation plans within a sequential process. The objective of this study is to develop a modelling framework that incorporates water and land management evolution within a spatially distributed hydrological model in order to produce projections that are more realistic on the water resources shortages. We applied this methodology on the Moselle River (North-East France) basin using climate projections derived from various representative concentration pathway scenarios (RCPs), general circulation models (GCM), and regional climate models (RCM) in a multi-scenario multi-model approach. Hydrological projections are computed from a conceptual hydrological model, and a recent R package (airGRiwrm) was used to account for anthropogenic water withdrawals. Through contrasting scenarios of water use evolution built in partnership with the water stakeholders, we are able to explore different evolutions of water demand for each type of use present in the Moselle basin (withdrawals for domestic and industrial uses, energy production, and waterway navigation). These scenarios allow us to feed the hydrological model with different water withdrawals, in addition to the climate scenarios. The results of this multi-scenario and multi-model impact study on the water resources will be used to evaluate the water management sustainability and the adaptation levers.

Les sous-communs, planification fugitive et étude noire est une série d'essais publiée en 2013 par deux amis, Stefano Harney et Fred Moten. Au fil de ces textes, les auteurs proposent une critique du capitalisme racial et de ses outils (gouvernance, crédit, université) ainsi que des modes d'expérimentation sociale en forme de résistance au colonial. La recherche passe par l'étude et se déroule bien au-delà de l'université, au travail, lors d'une pause cigarette, en famille, autour d'un repas, à la lisière de la lutte et de la fuite, à l'intérieur d'un mouvement de tremblement des fondations impérialistes, d'un mouvement de refus des termes du combat tel qu'il est imposé par le système dominant, vers la construction d'un espace social et politique en perpétuel déplacement. Le lieu et l'être sous-communs relèvent de l'incertitude de la création collective, de l'habitation par l'échange, de l'improvisation comme critique.Les sous-communs s'écrit dans le sillage de la tradition radicale noire de manière à la fois théorique et poétique, auprés d'auteur*ices comme Cedric Robinson, Saidiya Hartman, Frantz Fanon et Édouard Glissant .La multitude profite de chaque temps calme, chaque crépuscule, chaque instant de préservation militante, pour planifier ensemble, lancer, composer (dans) son temps surréel.- Moten et Harney, p. 92.Stefano Harney est chercheur en sociologie et enseignant. Co-fondateur de la résidence de lecture Ground Provisions et du collectif d'enseignant*es School for Study, il est l'auteur de The Liberal Arts and Management Education (2020), Nationalism & Identity Culture (2006) et State Work: Public Administration and Mass Intellectuality (2002).Fred Moten est poète et professeur au département de Performance Studies de l'Université de New York, Tisch School of the Arts. Il est l'auteur de la trilogie consent not to be a single being, The Universal Machine (2018) ; Stolen Life (2018) et Black and Blur, (2017) ; The Service Porch (2016) ; B Jenkins (2010) ; In the Break: The Aesthetics of the Black Radical Tradition (2003).

International audience

International audience; La température de l’eau est un facteur déterminant de la vie des rivières et conditionne les activités industrielles. L’objectif de l’étude est d’établir l’évolution de la température de la Seine à Paris depuis la fin du XIX siècle jusqu’à l’horizon 2100.L’exploitation statistique des observations déjà collectées ont mis en évidence les liens très forts entre température de l’air et la température de l’eau. Les conséquences du réchauffement climatique sont nettement visibles depuis la fin du XIX siècle jusqu’à nos jours : hausse de 1,7 °C par siècle des températures de la Seine, de la Marne, et de l’air.Les méthodes de Machine Learning, sont très efficaces pour l'exploration de jeux de données massifs et sont déjà utilisées en climatologie, météorologie ou hydrologie. Elles ont été retenues pour déterminer les futures températures jusqu’à l’horizon 2100. Les projections de température de l’air estimées à la station proche d’Orly par 12 instituts européens, selon 3 scénarios des émissions terrestres en CO2 (RCP 2.6, 4.5 et 8,5) ont été téléchargées depuis le site web DRIAS. Ces modélisations annoncent une accélération de la hausse notamment dans le scénario RCP 8.5 à l’horizon 2100 : augmentation de la température moyenne annuelle de 2,7 °C et multiplication par 3 des périodes chaudes (>24°C) depuis nos jours.

Les mutations des Facteurs II et/ou V Leiden confèrent au patient une thrombophilie. Cette dernière se caractérisant par une tendance biologique à présenter des épisodes thrombotiques.La vie d’une femme est marquée par des changements hormonaux, avec notamment 3 périodes charnières représentées par la contraception, la grossesse et la ménopause. L’utilisation de contraceptif œstroprogestatif a été largement décrite dans la littérature, et la sécurité vis-à-vis du risque thrombotique n’a pu être établi. En effet, malgré un risque qui diffère en fonction des générations, il ne peut être envisagé de prescrire une telle thérapie à une patiente mutée. Cette dernière se verra restreinte à l’utilisation de contraceptif progestatif (pilule, dispositif intra-utérin et implant) ou au cuivre. De plus, les modifications de l’hémostase inhérentes à l’état de gestation entrainent une situation d’hypercoagulabilité. Ainsi, une femme enceinte à l’allèle sauvage présente de part cette situation, un risque thrombotique avéré. Il est alors évident que la synergie entre thrombophilie et grossesse nécessite une prise en charge. Pour se faire, différents scores clinico-biologiques ainsi que des recommandations contribuent à prendre la décision d’instaurer une thromboprophylaxie anté et/ou post-partum. Enfin, le parcours hormonal se termine lors de la ménopause marquée par la chute des œstrogènes et ses diverses conséquences. En cas de symptomatologie bruyante, le recours aux THS doit se faire avec prudence. En effet, la littérature a démontré, un profil de sécurité complexe, qui autorise les patientes mutées à l’usage unique des formes transdermiques ou cutanées.

International audience; Ce rapport est le fruit d'un travail réalisé entre la DRIEAT et des scientifiques du PIREN Seine. La température de l’eau est un facteur déterminant de la vie des rivières et conditionne les activités industrielles. L’objectif de l’étude est d’établir l’évolution de la température de la Seine et de la Marne dans l’agglomération parisienne depuis la fin du XIX e siècle jusqu’à l’horizon 2100.L’exploitation statistique des observations déjà collectées ont mis en évidence les liens très forts entre température de l’air et la température de l’eau. Les conséquences du réchauffement climatique sont nettement visibles depuis la fin du XIX ème siècle jusqu’à nos jours : hausse de 1,7°C par siècle des températures de la Seine, de la Marne, et de l’air.Les méthodes de Machine Learning, sont très efficaces pour l'exploration de jeux de données massifs et sont déjà utilisées en climatologie, météorologie ou hydrologie. Elles ont été retenues pour déterminer les futures températures jusqu’à l’horizon 2100. Les projectionsde température de l’air estimées à la station proche d’Orly par 12 instituts européens, selon 3 scénarios des émissions terrestres en CO 2 (RCP 2.6, 4.5 et 8.5) ont été téléchargées depuis le site web DRIAS.Ces modélisations annoncent une accélération de la hausse notamment dans le scénario RCP 8.5 à l’horizon 2100 : augmentation de la température moyenne annuelle de 2,7°C et multiplication par 3 des périodes chaudes (>25,5°C) depuis nos jours.

Study region This study focused mainly on Burkina Faso in West Africa. Study focus This study aims to identify environmental variables that best explain the geographic variations of the flow intermittency regime, focusing on intermittency duration. Discharge data from 49 gauging stations were considered, mostly over large rivers. The mean number of dry months ( N d r y ¯ ) was used as a predictor to define four classes of flow intermittency, for which the potential explanatory environmental variables were assessed based on correlation analysis and principal component analysis (PCA). New hydrological insights for the region The first two components (PCs) account for 82 % of the total variance with PC1 (52 %), and most of the catchments with similar flow intermittency are ordered according to PC2 (30 %), predominantly related to catchment permeability. Moreover, permeability was highly correlated with N d r y ¯ (r = - 0.75). Results suggest that catchment permeability and catchment areas are the most critical variables in determining flow intermittency classes in Burkina Faso, as the effect of precipitation can be overruled by the ones of permeability, catchment area, and Strahler order. This study is a first step in understanding the controls of river intermittency in data-scarce and poorly gauged regions of West Africa. The identified variables could be used as input in statistical models to predict and map river intermittency and provide valuable information for stream conservation.

Summary The pharmaceutical industry faces a growing demand and recurrent shortages in many anticancer plant drugs given their extensive use in human chemotherapy. Efficient alternative strategies of supply of these natural products such as bioproduction by microorganisms are needed to ensure stable and massive manufacturing. Here, we developed and optimized yeast cell factories efficiently converting tabersonine to vindoline, a precursor of the major anticancer alkaloids vinblastine and vincristine. First, fine‐tuning of heterologous gene copies restrained side metabolites synthesis towards vindoline production. Tabersonine to vindoline bioconversion was further enhanced through a rational medium optimization (pH, composition) and a sequential feeding strategy. Finally, a vindoline titre of 266 mg l−1 (88% yield) was reached in an optimized fed‐batch bioreactor. This precursor‐directed synthesis of vindoline thus paves the way towards future industrial bioproduction through the valorization of abundant tabersonine resources., Saccharomyces was engineered for the precursor directed synthesis of vindoline by integrating the Catharanthus roseus vindoline biosynthetic genes into hotspots of the yeast genome. Fine‐tuning of genes copy numbers as well as optimization of culture conditions (medium composition, pH) improved tabersonine to vindoline conversion up to reaching a 266 mg l−1 vindoline production (88% yield).

International audience; Plant specialized metabolites are widely used in the pharmaceutical industry, including the monoterpene indole alkaloids (MIAs) vinblastine and vincristine, which both display anticancer activity. Both compounds can be obtained through the chemical condensation of their precursors vindoline and catharanthine extracted from leaves of the Madagascar periwinkle. However, the extensive use of these molecules in chemotherapy increases precursor demand and results in recurrent shortages, explaining why the development of alternative production approaches, such microbial cell factories, is mandatory. In this context, the precursor-directed biosynthesis of vindoline from tabersonine in yeast-expressing heterologous biosynthetic genes is of particular interest but has not reached high production scales to date. To circumvent production bottlenecks, the metabolic flux was channeled towards the MIA of interest by modulating the copy number of the first two genes of the vindoline biosynthetic pathway, namely tabersonine 16-hydroxylase and tabersonine-16-O-methyltransferase. Increasing gene copies resulted in an optimized methoxylation of tabersonine and overcame the competition for tabersonine access with the third enzyme of the pathway, tabersonine 3-oxygenase, which exhibits a high substrate promiscuity. Through this approach, we successfully created a yeast strain that produces the fourth biosynthetic intermediate of vindoline without accumulation of other intermediates or undesired side-products. This optimization will probably pave the way towards the future development of yeast cell factories to produce vindoline at an industrial scale.

Climate change might cause regional modifications of precipitation regimes and increase of air temperature and evaporative demand. As a consequence, the potential increase in evapotranspiration has been determined as a key risk, which could lead to a decrease in runoff and water resources. In many hydrological models, evapotranspiration is determined by a preliminary computation of the evaporative demand, potential evapotranspiration (PET). Estimating PET for future climate is still subject to extensive research, due to the multiplicity of PET formulations and the uncertainties associated with the climatic variables used within these formulations. Physically-based PET formulations use several climatic variables whose simulations come with large uncertainties, while more simple empirical PET formulations rely on limited climatic variables. However, their empiric development questions their robustness for transient climatic conditions.In this work, we examined the evolution of PET under future climate conditions. We also investigated to what extent seven different classical PET formulations could modify the partitioning of uncertainty associated with climate projections.The importance of PET formulation on the total uncertainty of the potential evapotranspiration changes was evaluated within a multiscenario multimodel ensemble (Euro-CORDEX climate projections from CMIP5 experiment) over the whole France. This approach was used to account for the uncertainty on the unknown future greenhouse gas emissions trajectories, and differences coming from climate models (GCMs and RCMs). An analysis of the variance (ANOVA), allowed us to determine the contribution of each modelling step to the total uncertainty of PET estimates over entire France. The ANOVA was applied on an ensemble completed by a Bayesian process, to have a balance set of projections to analyze.The results showed that the relative importance of PET formulations was found to be minor compared with other uncertainty sources (GCMs and RCMs) in the future. We also found that divergences of PET among the different formulations were highly dependent on the temperature anomaly. Based on our experimental design, we concluded that the choice of PET formulation might not constitute a major element of uncertainty reduction for hydrological projections.

Background Sickle cell disease (SCD) as other chronic medical conditions is commonly complicated by depression or other psychiatric symptoms. Results reported in studies present a large variation. Thus, synthetic data are needed to understand impact of depression in adults with SCD. The aim of this literature review is to analyse the methodology used in the studies assessing depression and discuss the different prevalence levels reported. Methods Studies involving adults with SCD from 1999 to 2018 were included when providing data on prevalence of depression. It was defined by a psychometric assessment, a structured interview, or a medical record review. PRISMA recommendations were followed. Results 36 studies are included accordingly to our methodology. Prevalence variation is large, from 0% to more than 85%. We find that the type of assessment tool used plays a major role in this between studies variation. Also, methodological issues arise with respect to psychometric assessment. Moreover, differences emerge between continents, setting of recruitment or time of assessment. Conclusion All these issues are discussed to provide insight on depression in adults with sickle cell disease. Trial Registration PROSPERO Registration CRD42018100684.

Introduction. Compliance to treatment is low in adult patients with sickle cell disease. The current literature is scarce and does not provide an explanation for understanding the low compliance rate. In other chronic diseases, the Leventhal model has been used to explain therapeutic compliance. Using Leventhal’s model as a theoretical framework, this study aims to explore the psychosocial factors predicting treatment compliance in adult patients with sickle cell disease.Method. The sample consisted of 517 adults. The data collected included several sociodemographic and medical variables, an assessment of the representation of sickle cell disease, treatment compliance and adherence, as well as symptomatic assessments of pain, fatigue, depression and anxiety. In addition, emotional functioning, coping strategies, locus of control and psychological functioning associated with pain were explored. Finally, ten semi-structured interviews were conducted aimed at exploring the subjective representation of sickle cell disease, treatment and pain.Results. The completed Leventhal model for sickle cell disease was confirmed in our sample and helps explain the variation in the level of treatment compliance. The representation of sickle cell disease has no direct effect on compliance, only indirect effects via coping strategies and beliefs about treatments. Pain and emotional functioning do not directly influence compliance to treatment, but only show indirect effects through coping strategies and beliefs about treatment. Symptomatologically, the level of fatigue and anxiety reported is very high, while the level of depression appears to be low compared to international studies. Finally, the hypothesis of the existence of a post-traumatic stress disorder is raised with regard to the results of the emotional processing evaluations.Conclusion. Confirmation of the completed Leventhal model for sickle cell disease provides a theoretical framework for understanding compliance in adults with sickle cell disease. The results show the importance of the impact of certain symptoms and suggest psychological interventions.; Introduction. L’observance thérapeutique est faible chez les patients adultes atteints de drépanocytose. La littérature actuelle est rare et ne donne pas d’explications pour comprendre la faiblesse du taux d’observance. Dans d’autres maladies chroniques, le modèle de Leventhal a permis d’expliquer l’observance thérapeutique. En utilisant le modèle de Leventhal comme cadre théorique, cette étude a comme objectif d’explorer les facteurs psychosociaux prédisant l’observance thérapeutique des patients adultes ayant la drépanocytose.Méthode. L’échantillon est composé de 517 adultes. Les données recueillies comprenaient plusieurs variables sociodémographiques et médicales, une évaluation de la représentation de la drépanocytose, de l’observance et de l’adhésion thérapeutiques, ainsi que des évaluations symptomatiques de la douleur, de la fatigue, de la dépression et de l’anxiété. En plus, le fonctionnement émotionnel, les stratégies de coping, le lieu de contrôle et le fonctionnement psychologique associé à la douleur ont été explorés. Enfin, dix entretiens semi-directifs ont été menés visant à explorer la représentation subjective de la drépanocytose, des traitements, de la douleur et de la prise en charge.Résultats. Le modèle de Leventhal complété pour la drépanocytose a été confirmé dans notre échantillon et permet d’expliquer la variation du niveau d’observance thérapeutique. La représentation de la drépanocytose n’a pas d’effet direct sur l’observance, mais uniquement des effets indirects via les stratégies de coping et les croyances sur les traitements. La douleur et le fonctionnement émotionnel n’influencent pas directement l’observance thérapeutique, mais présentent uniquement des effets indirects au travers des stratégies de coping et des croyances sur les traitements. D’un point de vue symptomatologique, le niveau de fatigue et d’anxiété rapporté est très élevé, tandis que le niveau de dépression apparaît faible par rapport aux études internationales. Enfin, l’hypothèse de l’existence d’un trouble de stress post-traumatique est évoquée au regard des résultats des évaluations du traitement émotionnel.Conclusion. La confirmation du modèle de Leventhal complété pour la drépanocytose offre un cadre théorique pour comprendre l’observance thérapeutique des adultes atteints de drépanocytose. Les résultats montrent l’importance de l’impact de certains symptômes et suggèrent des pistes d’intervention.

International audience; Olive growers in Andalusia are concerned about the impact of climate change on their activity, which is very important in terms of surface area, production and income. In an attempt to answer these questions, this work first describes the evolution of climate and annual yields of rainfed and irrigated olive groves in the province of Jaén (Andalusia) since the 1950s. Second, the relationships between rainfed and irrigated yields on one side and climatic variables on the other side are modelled. Finally, the models allow the calculation and mapping of the current theoretical spatial distribution of yields. Yields vary greatly from year to year, but are generally higher in irrigated than in rainfed orchards. Yields have risen sharply since the end of the 1950s, stabilizing since the end of the 1990s, with an average over the 1996-2018 period of 30 q/ha and 51 q/ha in irrigated and rainfed areas, respectively. Meanwhile, the mean temperatures over the olive growing area of the province of Jaén, have increased, especially for daytime and during the hot season. Rainfall, which is highly variable over the studied area, has decreased by 16% after 1979. Between 1996 and 2018, the climatic variables explaining best olive yields for rainfed areas are annual rainfall and minimum temperatures in autumn and August. Concerning irrigated areas, autumn rainfall and minimum temperatures, maximum summer temperatures and minimum February temperatures are the most relevant climatic variables. Theoretical yield values for rainfed and irrigated olive groves are calculated by multiple regression (1996-2018), validated by cross-validation. Theoretical yield values are then mapped on 4km side pixels. Although the simulated and averaged values (1996-2018) are close to the observed provincial values, with a mean error of 6 q/ha in irrigated and rainfed areas, their spatial distribution is not entirely consistent with some information available at the communal level. It will therefore be necessary to improve the modeling of yields and their mapping before moving on to the next step: simulating and mapping potential future yields, taking into account climate change, in order to have a tool for discussion with olive growers and to help them prepare the adaptation of their activity.; Les acteurs de l’oléiculture en Andalousie s’interrogent sur l’impact du changement climatique sur leur activité, très importante en termes de surfaces concernées, de production et de revenus. Pour tenter de leur répondre, ce travail décrit tout d’abord l’évolution du climat et des rendements annuels des oliveraies pluviales et irriguées dans la province de Jaén (Andalousie) depuis les années 50. Puis sont réalisées des modélisations des relations entre les rendements pluviaux et irrigués provinciaux et des variables climatiques TerraClimate (à résolution de 4 km), moyennées sur la zone oléicole de la province de Jaén. Enfin, les modèles permettent de calculer puis de cartographier la répartition théorique actuelle des rendements. Les rendements, très variables d’une année sur l’autre, plus élevés dans les vergers irrigués que dans les vergers pluviaux, ont fortement augmenté depuis la fin des années cinquante puis ils se sont stabilisés à partir de la fin des années 1990, avec en moyenne 30 q/ha en pluvial et 51 q/ha en irrigué pour la période 1996-2018. Par ailleurs, les températures, moyennées sur la zone oléicole de la province de Jaén, ont augmenté, surtout les températures diurnes, essentiellement durant la saison chaude. Les précipitations, très variables d’une année sur l’autre, ont diminué de 16% après 1979. Entre 1996 et 2018, les variables qui expliquent le mieux les rendements sont les pluies annuelles et les températures minimales d’automne et d’août dans les oliveraies pluviales, et les pluies et températures minimales d’automne, les températures maximales d’été et les températures minimales de février, dans les oliveraies irriguées. Des valeurs de rendement théoriques en pluvial et en irrigué sont calculées par régression multiple (1996-2018), validées par cross-validation. Les valeurs théoriques sont ensuite cartographiées sur des pixels de 4 km de côté. Si les valeurs simulées et moyennées (1996-2018) sont proches des valeurs provinciales observées, avec une erreur-moyenne de 6 q/ha en irrigué et en pluvial, leur répartition spatiale n’est pas tout à fait cohérente avec quelques informations disponibles à l’échelle communale. Il conviendra donc de perfectionner la modélisation des rendements et leur cartographie avant de passer à l’étape suivante : simuler et cartographier les rendements potentiels futurs, compte tenu du changement climatique, pour disposer d’un outil de discussion avec les oléiculteurs et les aider à préparer l’adaptation de leur activité.

Deglycosylation is a key step in the activation of specialized metabolites involved in plant defense mechanisms. This reaction is notably catalyzed by β-glucosidases of the glycosyl hydrolase 1 (GH1) family such as strictosidine β-d-glucosidase (SGD) from Catharanthus roseus. SGD catalyzes the deglycosylation of strictosidine, forming a highly reactive aglycone involved in the synthesis of cytotoxic monoterpene indole alkaloids (MIAs) and in the crosslinking of aggressor proteins. By exploring C. roseus transcriptomic resources, we identified an alternative splicing event of the SGD gene leading to the formation of a shorter isoform of this enzyme (shSGD) that lacks the last 71-residues and whose transcript ratio with SGD ranges from 1.7% up to 42.8%, depending on organs and conditions. Whereas it completely lacks β-glucosidase activity, shSGD interacts with SGD and causes the disruption of SGD multimers. Such disorganization drastically inhibits SGD activity and impacts downstream MIA synthesis. In addition, shSGD disrupts the metabolic channeling of downstream biosynthetic steps by hampering the recruitment of tetrahydroalstonine synthase in cell nuclei. shSGD thus corresponds to a pseudo-enzyme acting as a regulator of MIA biosynthesis. These data shed light on a peculiar control mechanism of β-glucosidase multimerization, an organization common to many defensive GH1 members.

High-quality developmental environments often improve individual performance into adulthood, but allocating toward early life traits, such as growth, development rate and reproduction, may lead to trade-offs with late-life performance. It is, therefore, uncertain how a rich developmental environment will affect the ageing process (senescence), particularly in wild insects. To investigate the effects of early life environmental quality on insect life-history traits, including senescence, we reared larval antler flies ( Protopiophila litigata ) on four diets of varying nutrient concentration, then recorded survival and mating success of adult males released in the wild. Declining diet quality was associated with slower development, but had no effect on other life-history traits once development time was accounted for. Fast-developing males were larger and lived longer, but experienced more rapid senescence in survival and lower average mating rate compared to slow developers. Ultimately, larval diet, development time and body size did not predict lifetime mating success. Thus, a rich environment led to a mixture of apparent benefits and costs, mediated by development time. Our results indicate that ‘silver spoon' effects can be complex and that development time mediates the response of adult life-history traits to early life environmental quality.

Grape canes are under-valued byproducts of viticulture that accumulate large amounts of stilbenoids. These specialized metabolites are phytoalexins of Vitis vinifera that play a keyrole in defence of Vitis vinifera against pathogens. Since in vitro assays demonstrated the antifungal activity of several pure stilbenoids, grape cane extracts (GCE) have been proposed as eco-friendly alternative to classical fungicides in a context of sustainable viticulture. Following the grape pruning during winter, a storage period associated to an efficient extraction procedure, are determinant to obtain GCE with optimal stilbenoid titration. Stilbenoid-enriched extracts have shown promising protection in vitro against various grape pathogens including downy mildew, powdery mildew, gray mold and wood diseases. Additionally, large-scale studies in vineyards reported a significant partial protection against downy mildew. Protection level is relative to the concentration of stilbenoids contained in the grape cane extract. Therefore, the huge varietal diversity of grape could be explored to select high-producing varieties for future use as biocontrol agent.

International audience; Landscape differences induced by urbanization have prompted hydrologists to define a fuzzy boundary between rural‐ and urban‐specific hydrological models. We addressed the validity of establishing this boundary, by testing two rural models on a large sample of 175 French and United States (US) urbanized catchments, and their 175 rural neighbours. The impact of urbanization on the hydrological behaviour was checked using four metrics. Using a split‐sample test, we have compared the performances, parameter distributions, and internal fluxes of GR4H and IHACRES, two conceptual and continuous models running at the hourly time step. Both model structures are based on soil moisture accounting reservoirs (infiltration, runoff, and actual evapotranspiration) and quick flow/slow flow routing components, with no consideration of any specific feature related to urbanization. Results showed: (a) Except for the ratio of streamflow flashiness to precipitation flashiness, the range of hydrological signature metrics in rural catchments encompassed the specificities of urbanized ones. Overall, the urbanized catchments showed higher ratios of mean streamflow to mean precipitation (median values: 0.39 vs. 0.27) and streamflow flashiness to precipitation flashiness (0.13 vs. 0.03), besides lower baseflow index (0.42 vs. 0.62) and shorter characteristic response time (3 vs. 14 hr). (b) The performances of GR4H revealed no significant distinction between rural and urbanized catchments in terms of Kling–Gupta Efficiency (KGE), whereas IHACRES better simulated urbanized catchments, especially during summer. (c) With respect to differences in urbanization level, the GR4H and IHACRES parameters showed different distributions. The differences in parameters were consistent with the differences in hydrological behaviour, which is promising for a model‐based assessment of the impact of urbanization. (d) The models agreed less in reproducing the internal fluxes over the urbanized catchments than over the rural ones. These results demonstrate the flexibility of conceptual models to handle the specificities of urbanized catchments.

Monoterpene indole alkaloids (MIAs) are specialized metabolites synthesized in many plants of the Apocynaceae family including Catharanthus roseus and Rauvolfia sp. MIAs are part of the chemical arsenal that plants evolved to face pet and herbivore attacks, and their high biological activities also confer pharmaceutical properties exploited in human pharmacopeia. Developing robust and straightforward tools to elucidate each step of MIA biosynthetic pathways thus constitutes a prerequisite to the understanding of Apocynaceae defense mechanisms and to the exploitation of MIA cytotoxicity through their production by metabolic engineering. While protocols of virus-induced gene silencing (VIGS) based on Agrobacterium-based transformation have emerged, the recalcitrance of Apocynaceae to this type of transformation prompted us to develop an universal procedure of VIGS vector inoculation. Such procedure relies on the delivery of the transforming plasmids through a particle bombardment performed using a biolistic device and offers the possibility to overcome host specificity to silence genes in any plant species. Using silencing of geissoschizine oxidase as an example, we described the main steps of this biolistic mediated VIGS in C. roseus and R. tetraphylla.

Virus-induced gene silencing (VIGS) is a fast and efficient tool to investigate gene function in plant as an alternative to knock down/out transgenic lines, especially in plant species difficult to transform and challenging to regenerate such as perennial woody plants. In apple tree, a VIGS vector has been previously developed based on the Apple latent spherical virus (ALSV) and an efficient inoculation method has been optimized using biolistics. This report described detailed step-by-step procedure to design and silence a gene of interest (GOI) in apple tree tissues using the ALSV-based vector.

We provide first evidence that a heterozygous NOP10 mutation (c.17A>G,p.Tyr6Cys) identified in a large family co-segregates with adult-onset familial PF and predisposes to short telomere syndrome (familial PF, liver, haematological diseases)http://bit.ly/2wvXsUd

Nowadays, the characterization of greenhouse gases (such as CO₂, CH₄, NOₓ) on a global scale is a major issue. Identifying the sources and sinks of these various chemical species using high precision instruments is today the subject of studies. The development of spectroscopic instruments with broad spectral coverage, precise and sensitive is thus necessary. The femto second frequency comb lasers used in Dual Comb Spectroscopy (DCS) makes possible to perform multi-species measurements over a wide spectral coverage.The main goal of this thesis is to evaluate the performance of a DCS system consisting of two femtosecond frequency comb MenloSystems Lasers as well as to implement integrated measurements of greenhouse gas concentrations in the atmosphere. A second objective is to study the feasibility of spatially resolved gas concentration measurements by backscattering light onto aerosols. To achieve these objectives the manuscript is organized as follows:- Evaluation of the performance of the DCS system available in the laboratory. Definition of a measurement protocol and first implementation of gas concentration measurement in a gas cell.- Implementation of the system for measurements of integrated gas concentrations in the atmosphere. First with the measurement of water vapor concentration on short-range (27 m). Then on medium-range (140 m) with multi-species concentration measurement on water vapor and carbon dioxide.- Assessment of the ability to perform Lidar IPDA and DiAL measurements using DCS. In the first part we estimate the performance of our system in terms of measurement range for Lidar IPDA measurement using a diffuse target. In a second part, we are interested in aerosol backscatter measurements. We describe the incompatibility of high repetiton rate laser with the traditional method of locating pulses by their time of flight. Two solutions are proposed to circumvent this difficulty.; De nos jours la caractérisation des gaz à effet de serre (telle que CO₂, CH₄ , les NOₓ ) à l'échelle mondiale est un enjeux majeur. Identifier les sources et puits de ces diverses espèces chimiques à l'aide d'instruments de grande précision est aujourd'hui l'objet d'études approfondies. Le développement d'instruments spectroscopiques de large couverture spectrale, précis et sensibles est ainsi nécessaire. Les laser femto secondes peigne de fréquences utilisés en Dual Comb Spectroscopy (DCS) permettent de réaliser des mesures multi-espèces sur une large couverture spectrale.L'objectif principal de cette thèse est d'évaluer les performances d'un système de DCS composé de deux laser femtosecondes peigne de fréquences MenloSystems ainsi que de mettre en oeuvre des mesures intégrées de concentrations de gaz à effet de serre dans l'atmosphère. Un deuxième objectif consiste à étudier la faisabilité de réaliser des mesures de concentration de gaz résolues spatialement grâce à la rétrodiffusion de la lumière sur des aérosols. Pour atteindre ces objectifs le manuscrit est organisé de la manière suivante:- Evaluation des performances du système DCS disponible au laboratoire. Définition d'un protocol de mesure et première mise en oeuvre de mesure de concentration de gaz en cellule de gaz.- Mise en oeuvre du système pour des mesures de concentrations intégrées de gaz en atmosphère. Tout d'abord avec la mesure de concentration de la vapeur d'eau à courte portée (27 m). Puis la mesure de concentration multi-espèces à moyenne portée (140 m) sur la vapeur d'eau et le dioxyde de carbone.-Evaluation de la capacité à réaliser des mesures Lidar IPDA et DiAL en utilisant la DCS. Dans une première partie nous estimons les performances en terme de portée pour notre système de mesures Lidar IPDA utilisant une cible diffuse. Dans une seconde partie on s'intéresse aux mesures en rétrodiffusion sur les aérosols. Nous décrivons l'incompatibilité des lasers hautes cadences avec la méthode classique de localisation des impulsions par leur temps de vol. Deux solutions sont proposées pour contourner cette difficulté.

Nowadays, the characterization of greenhouse gases (such as CO₂, CH₄, NOₓ) on a global scale is a major issue. Identifying the sources and sinks of these various chemical species using high precision instruments is today the subject of studies. The development of spectroscopic instruments with broad spectral coverage, precise and sensitive is thus necessary. The femto second frequency comb lasers used in Dual Comb Spectroscopy (DCS) makes possible to perform multi-species measurements over a wide spectral coverage.The main goal of this thesis is to evaluate the performance of a DCS system consisting of two femtosecond frequency comb MenloSystems Lasers as well as to implement integrated measurements of greenhouse gas concentrations in the atmosphere. A second objective is to study the feasibility of spatially resolved gas concentration measurements by backscattering light onto aerosols. To achieve these objectives the manuscript is organized as follows:- Evaluation of the performance of the DCS system available in the laboratory. Definition of a measurement protocol and first implementation of gas concentration measurement in a gas cell.- Implementation of the system for measurements of integrated gas concentrations in the atmosphere. First with the measurement of water vapor concentration on short-range (27 m). Then on medium-range (140 m) with multi-species concentration measurement on water vapor and carbon dioxide.- Assessment of the ability to perform Lidar IPDA and DiAL measurements using DCS. In the first part we estimate the performance of our system in terms of measurement range for Lidar IPDA measurement using a diffuse target. In a second part, we are interested in aerosol backscatter measurements. We describe the incompatibility of high repetiton rate laser with the traditional method of locating pulses by their time of flight. Two solutions are proposed to circumvent this difficulty.; De nos jours la caractérisation des gaz à effet de serre (telle que CO₂, CH₄ , les NOₓ ) à l'échelle mondiale est un enjeux majeur. Identifier les sources et puits de ces diverses espèces chimiques à l'aide d'instruments de grande précision est aujourd'hui l'objet d'études approfondies. Le développement d'instruments spectroscopiques de large couverture spectrale, précis et sensibles est ainsi nécessaire. Les laser femto secondes peigne de fréquences utilisés en Dual Comb Spectroscopy (DCS) permettent de réaliser des mesures multi-espèces sur une large couverture spectrale.L'objectif principal de cette thèse est d'évaluer les performances d'un système de DCS composé de deux laser femtosecondes peigne de fréquences MenloSystems ainsi que de mettre en oeuvre des mesures intégrées de concentrations de gaz à effet de serre dans l'atmosphère. Un deuxième objectif consiste à étudier la faisabilité de réaliser des mesures de concentration de gaz résolues spatialement grâce à la rétrodiffusion de la lumière sur des aérosols. Pour atteindre ces objectifs le manuscrit est organisé de la manière suivante:- Evaluation des performances du système DCS disponible au laboratoire. Définition d'un protocol de mesure et première mise en oeuvre de mesure de concentration de gaz en cellule de gaz.- Mise en oeuvre du système pour des mesures de concentrations intégrées de gaz en atmosphère. Tout d'abord avec la mesure de concentration de la vapeur d'eau à courte portée (27 m). Puis la mesure de concentration multi-espèces à moyenne portée (140 m) sur la vapeur d'eau et le dioxyde de carbone.-Evaluation de la capacité à réaliser des mesures Lidar IPDA et DiAL en utilisant la DCS. Dans une première partie nous estimons les performances en terme de portée pour notre système de mesures Lidar IPDA utilisant une cible diffuse. Dans une seconde partie on s'intéresse aux mesures en rétrodiffusion sur les aérosols. Nous décrivons l'incompatibilité des lasers hautes cadences avec la méthode classique de localisation des impulsions par leur temps de vol. Deux solutions sont proposées pour contourner cette difficulté.

This article belongs to the Special Issue Biosynthesis and Function of Plant Specialized Metabolites., The Madagascar periwinkle (Catharanthus roseus) synthesizes the highly valuable monoterpene indole alkaloids (MIAs) through a long metabolic route initiated by the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. In leaves, a complex compartmentation of the MIA biosynthetic pathway occurs at both the cellular and subcellular levels, notably for some gene products of the MEP pathway. To get a complete overview of the pathway organization, we cloned four genes encoding missing enzymes involved in the MEP pathway before conducting a systematic analysis of transcript distribution and protein subcellular localization. RNA in situ hybridization revealed that all MEP pathway genes were coordinately and mainly expressed in internal phloem-associated parenchyma of young leaves, reinforcing the role of this tissue in MIA biosynthesis. At the subcellular level, transient cell transformation and expression of fluorescent protein fusions showed that all MEP pathway enzymes were targeted to plastids. Surprisingly, two isoforms of 1-deoxy-D-xylulose 5-phosphate synthase and 1-deoxy-D-xylulose 5-phosphate reductoisomerase initially exhibited an artifactual aggregated pattern of localization due to high protein accumulation. Immunogold combined with transmission electron microscopy, transient transformations performed with a low amount of transforming DNA and fusion/deletion experiments established that both enzymes were rather diffuse in stroma and stromules of plastids as also observed for the last six enzymes of the pathway. Taken together, these results provide new insights into a potential role of stromules in enhancing MIA precursor exchange with other cell compartments to favor metabolic fluxes towards the MIA biosynthesis., We acknowledge funding from ARD2020 Biopharmaceutical program of the Région Centre Val de Loire (BioPROPHARM and CatharSIS projects). G.G. acknowledges a research fellowship of Le Studium-Institute for Advanced Studies, Loire Valley, Orléans, France.

International audience; This study aims to quantify the climate change impact on water resources in Jaén province (Andalousia) where 80% of the Spanish olive oil is produced in orchard that are partially irrigated, using surface water resources. The evolution of rainfall and temperature is assessed between historical and future period based on 6 climate projections. The projected climatic conditions show a 1.4°C temperature increase and a 10% rainfall reduction by 2050.The projected climatic variables are then used as inputs of a hydrologic model in order to get a preliminary future flows estimation. In Andalusia, flow simulation represents a methodological challenge given the intense anthropogenic modifications of hydrographic network and water abstraction for irrigation. The results suggest a 21% decrease in flow (mainly observed in winter) and a dry season extension.; Cette étude a pour objectif de quantifier l’impact du changement climatique sur les ressources en eau de la province de Jaén (Andalousie), où 80 % de l’huile d’olive espagnole est produite en partie dans les verges irrigués par des eaux de surface. L’évolution des pluies et des températures est évaluée entre une période historique et future en se basant sur 6 projections climatiques régionales. Les projections climatiques indiquent une augmentation de la température de 1,4°C et une réduction des précipitations de 10% à l’horizon 2050.Ces projections climatiques sont ensuite utilisées en entrées d’un modèle hydrologique afin d’avoir une première estimation des débits futurs.En Andalousie, la simulation des débits représente un défi méthodologique compte-tenu de l’extrême artificialisation des réseaux hydrographiques et des prélèvements en eau destinés à l’irrigation.Les résultats obtenus suggèrent une diminution moyenne des débits de 21 % (principalement observés en hiver) et un allongement de la saison sèche.

BACKGROUND Plasmopara viticola control in organic viticulture requires copper-based fungicides with harmful effects on health and the environment. Plant extracts represent a biorational eco-friendly alternative to copper. The aim of this study was to evaluate the potential of stilbenoid-rich grape cane extract (GCE) against downy mildew on three cultivars over 3 years following natural downy mildew infection. RESULTS Over all field trials, GCE treatments showed an average reduction in disease incidence of -35% and -38% on leaves and clusters, respectively. The average reduction in disease severity was -35% and -43% on leaves and clusters, respectively. Under artificial downy mildew infection, GCE efficacy corresponded to 1 g L-1 of copper. Neither phytotoxicity nor adverse effects on auxiliary fauna were observed after treatment with GCE. CONCLUSION Because few or no biocontrol agents are active alone against P. viticola, GCE is a promising alternative to copper-based fungicides. Grape canes, an abundant by-product of viticulture, have great potential for valorization as a biocontrol agent for sustainable viticulture. © 2018 Society of Chemical Industry.

Background/objective The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children’s irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors. Design We compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI. Subjects/methods Body fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture. Results Patients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation. Conclusions These results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.

International audience; Several models can be used in order to represent the hydrological processes in an urbanized catchment. Developing those models has been with respect to modeling objectives, spatiotemporal scale and hydroclimatic and spatial data availability. These models can be explicit, hence complex and data demanding, or rather implicit, but lacking direct linking between the model parameters and the urbanization features. Leaning toward simplicity, we aim at developing an efficient modeling tool that permits implicitly to take into account the spatial configuration (urban landscape vs. natural surfaces) and temporal evolution at the scale of an urbanized hydrological catchment. Development of such tool can be achieved by complexifying step-by-step a starting model structure that is not dedicated to urbanized contexts. Before conducting structure modifications, the first step to take is to determine which model functions can be modified. In this paper, we analyze the initial structure and the sensitivity of the parameters that it contains to the presence of urban surfaces within the catchment. For this end, a large sample of 365 French and American catchments was prepared. These catchments are of various sizes going from 1 to 5000 km2 and represent a large panel of hydroclimatic conditions. The model was calibrated on two periods for each catchment, leading to 730 catchment-period couples for which the fraction of the urban cover was determined. The sensitivity analysis of the model parameters and other hydrological indicators with respect to this fraction was conducted for a selection of area-homogeneous 416 catchment-period couples. The results of this empirical study have shown (1) good model performances at the hourly time step regardless of the urban condition of the catchment and (2) that the model parameters and the hydrological indicators are significantly different with regards to intensively or slightly urbanized catchments, reflecting faster and greater streamflows for intensively urbanized situations.; Plusieurs modèles peuvent être utilisés pour représenter les processus hydrologiques en milieu urbain. Ces modèles sont développés suivant différentes approches en fonction de l'objectif de modélisation, de l'échelle spatio-temporelle et de la disponibilité des données hydroclimatiques et spatiales. Dans cet article, nous proposons de développer un outil parcimonieux et généralisable à partir d'une structure de modèle non dédié au contexte urbanisé. Dans un premier temps, nous analysons la structure de départ et la sensibilité des paramètres qu'elle contient à la présence de surfaces urbaines dans le bassin versant. Pour ce faire, un échantillon de 365 bassins versants français et américains a été construit. Le modèle est calé sur deux périodes pour chaque bassin versant, donnant ainsi 730 couples bassin-période pour lesquels la fraction urbaine dans le bassin a été déterminée. L'analyse de la sensibilité des paramètres du modèle hydrologique par rapport à cette fraction ainsi que d'autres indicateurs hydrologiques a été effectuée pour une sélection de 416 couples bassin-période, homogènes en surface. Les résultats montrent que les paramètres du modèle et les indicateurs hydrologiques présentent des différences significatives entre un échantillon de bassins versants fortement urbanisés et un échantillon de bassins versants faiblement urbanisés, traduisant des écoulements plus rapides et plus importants sur les bassins fortement urbanisés.

The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central- [TCM], transitional- [TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flow-cytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log10 copies/106 cells [IQR: 1.99–2.94]) but in TCM from only 1 individual (1.75 log10 copies/106 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log10 copies/106 PBMC [IQR = 1.53–2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed by FACS analysis, and a higher expression of TRIM5 transcripts (p = 0.004). Thus the low HIV-2 reservoirs differ from HIV-1 reservoirs by the lack of monocytic infection and a limited infection of TCM associated to a lower expression of a potential alternative HIV-2 co-receptor, CXCR6 and a higher expression of a restriction factor, TRIM5. These findings shed new light on the low pathogenicity of HIV-2 infection suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models., Author summary HIV-2 induces a still poorly understood attenuated infection compared to HIV-1. We investigated whether this infection might follow peculiarities associated with other models of attenuated HIV-1/SIV infection, i.e. a limited infection of a key subset of memory CD4 T lymphocytes, the central-memory ones (TCM). Thus we studied the infection rates in peripheral blood cells from 14 untreated HIV-2 infected individuals from the ANRS-CO5 HIV-2 cohort, and found; 1) a lack of infection of monocytes, 2) extremely low infection in central-memory CD4+ T lymphocytes while HIV-2 predominated in the transitional-memory cells, 3) a poor replicative capacity of HIV-2 in individuals cells. We then investigated the cellular expression of a hundred-host genes potentially involved in HIV-2 control. We found in individuals’ TCM cells, compared to TTM ones, a lower expression of CXCR6, a potentially alternative co-receptor of HIV-2 but not of HIV-1, and a higher expression of TRIM5α, a restriction factor to which HIV-2 is more sensitive than HIV-1. Altogether our findings shed new light on the low pathogenicity of HIV-2 suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models.

International audience; The influence of low temperatures on the performance of a high-power single-frequency fiber laser amplifier is evaluated with a numerical simulation. Cooling the fiber can allow to take advantage of both higher damping of the acoustic waves in the silica glass, and higher laser efficiency. We first report on the measurement of the stimulated Brillouin scattering (SBS) threshold in a silica fiber as a function of the temperature from 300 K down to 77 K. We then present the measurements of small-signal absorption and gain spectra of an erbium doped alumino-phosphosilicate fiber, at room temperature and liquid nitrogen temperature. Based on these data, we derive a numerical study of the combined effects of cooling on the SBS threshold and the amplifier efficiency, and conclude on the interest of this technique for SBS limited high power Er doped fiber amplifiers (EDFA). The temperature increase caused by the pump laser in the fiber core is also addressed.

International audience; Cytokinins (CK) have been extensively studied for their roles in plant development. Recently, they also appeared to ensure crucial functions in the pathogenicity of some bacterial and fungal plant pathogens. Thus, identifying cytokinin-producing pathogens is a prerequisite to gain a better understanding of their role in pathogenicity. Taking advantage of the cytokinin perception properties of Malus domestica CHASE Histidine Kinase receptor 2 (MdCHK2), we thereby developed a selective and highly sensitive yeast biosensor for the application of cytokinin detection in bacterial samples. The biosensor is based on the mutated sln1Δ Saccharomyces cerevisiae strain expressing MdCHK2. The biosensor does not require any extraction or purification steps of biological samples, enabling cytokinin analysis directly from crude bacterial supernatants. For the first time, the production of cytokinin was shown in the well-known plant pathogenic bacteria Erwinia amylovora and was also revealed in human pathogens Staphylococcus aureus and Streptococcus agalactiae. Importantly, this biosensor was shown to be an efficient tool for unraveling certain steps in cytokinin biosynthesis by micro-organisms since this it was successfully used to unveil the role of ygdH22, a LOG-like gene, that is probably involved in cytokinin biosynthesis pathway in Escherichia coli. Overall, we demonstrated that our biosensor displays several advantages including time- and cost-effectiveness by allowing a rapid and specific detection of cytokinins in bacterial supernatants These results also support its scalability to high-throughput formats.

The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central- [TCM], transitional- [TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flow-cytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log10 copies/106 cells [IQR: 1.99-2.94]) but in TCM from only 1 individual (1.75 log10 copies/106 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log10 copies/106 PBMC [IQR = 1.53-2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed by FACS analysis, and a higher expression of TRIM5 transcripts (p = 0.004). Thus the low HIV-2 reservoirs differ from HIV-1 reservoirs by the lack of monocytic infection and a limited infection of TCM associated to a lower expression of a potential alternative HIV-2 co-receptor, CXCR6 and a higher expression of a restriction factor, TRIM5. These findings shed new light on the low pathogenicity of HIV-2 infection suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models.

International audience; An amphiphilic polymer (CmPOX) based on poly(2-methyl-2-oxazoline) linked to a hydrophobic part composed of an aliphatic chain ended by a photo-active coumarin group has been synthesized. It exhibits the ability of forming small polymeric self-assemblies, typically of ca. 10 nm in size which were characterized by TEM, cryo-TEM and DLS. The nanocarriers were further formulated to yield photo-crosslinked systems by dimerization of coumarin units of a coumarinfunctionalized poly(methyl methacrylate) (CmPMMA) and CmPOX. The formed vectors were used to encapsulate Pheophorbide a, a known photosensitizer for PhotoDynamic Therapy. Cytotoxicity as well as photooxicity experiments led in vitro on human tumor cells revealed the great potential of these nanovectors for photodynamic therapy.

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Hemochromatosis type 4 is one of the most common causes of primary iron overload, after HFE-related hemochromatosis. It is an autosomal dominant disorder, primarily due to missense mutations in SLC40A1 This gene encodes ferroportin 1 (FPN1), which is the sole iron export protein reported in mammals. Not all heterozygous missense mutations in SLC40A1 are disease-causing. Due to phenocopies and an increased demand for genetic testing, rare SLC40A1 variations are fortuitously observed in patients with a secondary cause of hyperferritinemia. Structure/function analysis is the most effective way of establishing causality when clinical and segregation data are lacking. It can also provide important insights into the mechanism of iron egress and FPN1 regulation by hepcidin. The present study aimed to determine the pathogenicity of the previously reported p.Arg178Gln variant. We present the biological, clinical, histological and radiological findings of 22 patients from six independent families of French, Belgian or Iraqi decent. Despite phenotypic variability, all patients with p.Arg178Gln had elevated serum ferritin concentrations and normal to low transferrin saturation levels. In vitro experiments demonstrated that the p.Arg178Gln mutant reduces the ability of FPN1 to export iron without causing protein mislocalization. Based on a comparative model of the 3D structure of human FPN1 in an outward facing conformation, we argue that p.Arg178 is part of an interaction network modulating the conformational changes required for iron transport. We conclude that p.Arg178Gln represents a new category of loss-of-function mutations and that the study of "gating residues" is necessary in order to fully understand the action mechanism of FPN1. ispartof: HAEMATOLOGICA vol:103 issue:11 pages:1796-1805 ispartof: location:Italy status: published

Lochnericine is a major monoterpene indole alkaloid (MIA) in the roots of Madagascar periwinkle (Catharanthus roseus). Lochnericine is derived from the stereoselective C6,C7-epoxidation of tabersonine and can be metabolized further to generate other complex MIAs. While the enzymes responsible for its downstream modifications have been characterized, those involved in lochnericine biosynthesis remain unknown. By combining gene correlation studies, functional assays, and transient gene inactivation, we identified two highly conserved P450s that efficiently catalyze the epoxidation of tabersonine: tabersonine 6,7-epoxidase isoforms 1 and 2 (TEX1 and TEX2). Both proteins are quite divergent from the previously characterized tabersonine 2,3-epoxidase and are more closely related to tabersonine 16-hydroxylase, involved in vindoline biosynthesis in leaves. Biochemical characterization of TEX1/2 revealed their strict substrate specificity for tabersonine and their inability to epoxidize 19-hydroxytabersonine, indicating that they catalyze the first step in the pathway leading to horhammericine production. TEX1 and TEX2 displayed complementary expression profiles, with TEX1 expressed mainly in roots and TEX2 in aerial organs. Our results suggest that TEX1 and TEX2 originated from a gene duplication event and later acquired divergent, organ-specific regulatory elements for lochnericine biosynthesis throughout the plant, as supported by the presence of lochnericine in flowers. Finally, through the sequential expression of TEX1 and up to four other MIA biosynthetic genes in yeast, we reconstituted the 19-acetylhorhammericine biosynthetic pathway and produced tailor-made MIAs by mixing enzymatic modules that are naturally spatially separated in the plant. These results lay the groundwork for the metabolic engineering of tabersonine/lochnericine derivatives of pharmaceutical interest.

International audience; Lochnericine is a major monoterpene indole alkaloid (MIA) in the roots of Madagascar periwinkle (Catharanthus roseus). Lochnericine is derived from the stereoselective C6,C7-epoxidation of tabersonine and can be metabolized further to generate other complex MIAs. While the enzymes responsible for its downstream modifications have been characterized, those involved in lochnericine biosynthesis remain unknown. By combining gene correlation studies, functional assays, and transient gene inactivation, we identified two highly conserved P450s that efficiently catalyze the epoxidation of tabersonine: tabersonine 6,7-epoxidase isoforms 1 and 2 (TEX1 and TEX2). Both proteins are quite divergent from the previously characterized tabersonine 2,3-epoxidase and are more closely related to tabersonine 16-hydroxylase, involved in vindoline biosynthesis in leaves. Biochemical characterization of TEX1/2 revealed their strict substrate specificity for tabersonine and their inability to epoxidize 19-hydroxytabersonine, indicating that they catalyze the first step in the pathway leading to hörhammericine production. TEX1 and TEX2 displayed complementary expression profiles, with TEX1 expressed mainly in roots and TEX2 in aerial organs. Our results suggest that TEX1 and TEX2 originated from a gene duplication event and later acquired divergent, organ-specific regulatory elements for lochnericine biosynthesis throughout the plant, as supported by the presence of lochnericine in flowers. Finally, through the sequential expression of TEX1 and up to four other MIA biosynthetic genes in yeast, we reconstituted the 19-acetylhörhammericine biosynthetic pathway and produced tailor-made MIAs by mixing enzymatic modules that are naturally spatially separated in the plant. These results lay the groundwork for the metabolic engineering of tabersonine/lochnericine derivatives of pharmaceutical interest.

International audience; Grape accumulates numerous polyphenols with abundant health benefit and organoleptic properties that in planta act as key components of the plant defense system against diseases. Considerable advances have been made in the chemical characterization of wine metabolites particularly volatile and polyphenolic compounds. However, the metabotyping (metabolite-phenotype characterization) of grape varieties, from polyphenolic-rich vineyard by-product is unprecedented. As this composition might result from the complex interaction between genotype, environment and viticultural practices, a field experiment was setting up with uniform pedo-climatic factors and viticultural practices of growing vines to favor the genetic determinism of polyphenol expression. As a result, UPLC-MS-based targeted metabolomic analyses of grape stems from 8 Vitis vinifera L. cultivars allowed the determination of 42 polyphenols related to phenolic acids, flavonoids, procyanidins, and stilbenoids as resveratrol oligomers (degree of oligomerization 1-4). Using a partial least-square discriminant analysis approach, grape stem chemical profiles were discriminated according to their genotypic origin showing that polyphenol profile express a varietal signature. Furthermore, hierarchical clustering highlights various degree of polyphenol similarity between grape varieties that were in agreement with the genetic distance using clustering analyses of 22 microsatellite DNA markers. Metabolite correlation network suggested that several polyphenol subclasses were differently controlled. The present polyphenol metabotyping approach coupled to multivariate statistical analyses might assist grape selection programs to improve metabolites with both health-benefit potential and plant defense traits.

International audience; Studies quantifying the impact of climate change have so far mostly examined atmospheric variables, and few are evaluating the cascade of aquatic impacts that will occur along the land–ocean continuum until the ultimate impacts on coastal eutrophication potential. In this study, a new hydro-biogeochemical modeling chain has been developed, based on the coupling of the generic pyNuts-Riverstrahler biogeochemical model and the GR4J-CEMANEIGE hydrological model, and applied to the Seine River basin (France). Averaged responses of biogeochemical variables to climate-induced hydrological changes were assessed using climate forcing based on 12 projections of precipitation and temperature (BC-CORDEX) for the stabilization (RCP 4.5) and the increasing (RCP 8.5) CO2 emission scenarios. Beyond the amount of nutrients delivered to the sea, we calculated the indicator of coastal eutrophication potential (ICEP). The models run with the RCP4.5 stabilization scenario show low variations in hydrological regimes and water quality, while five of the six models run with the increasing CO2 emissions scenario (RCP8.5) leads to more intense extreme streamflow (i.e., higher maximum flows, lower and longer minimum flows), resulting in the degradation of water quality. For the driest RCP 8.5 projection, median biogeochemical impacts induced by decreasing discharge (until −270 m3 s−1 in average) are mostly located downstream of major wastewater treatment plants. During spring bloom, e.g., in May, the associated higher residence time leads to an increase of phytoplankton biomass (+31% in average), with a simultaneous −23% decrease of silicic acid, followed downstream by a −9% decrease of oxygen. Later during low flow, major increases in nitrate and phosphate concentrations (until +19% and +32% in average) are expected. For all considered scenarios, high ICEP values (above zero) lasted, indicating that coastal eutrophication is not expected to decrease with changing hydrological conditions in the future. Maximum values are even expected to be higher some years. This study deliberately evaluates the impact of modified hydrology on biogeochemistry without considering the simultaneous alteration of water temperatures, in order to disentangle the causes of climate change-induced impact. It will serve as a first comparative step toward a more complete modeling experiment of climate change impacts on aquatic systems.

International audience; While the characterization of the biosynthetic pathway of monoterpene indole alkaloids (MIAs) in leaves of Catharanthus roseus is now reaching completion, only two enzymes from the root counterpart dedicated to tabersonine metabolism have been identified to date, namely tabersonine 19-hydroxylase (T19H) and minovincine 19-O-acetyltransferase (MAT). Albeit the recombinant MAT catalyzes MIA acetylation at low efficiency in vitro, we demonstrated that MAT was inactive when expressed in yeast and in planta, suggesting an alternative function for this enzyme. Therefore, through transcriptomic analysis of periwinkle adventitious roots, several other BAHD acyltransferase candidates were identified based on the correlation of their expression profile with T19H and found to localize in small genomic clusters. Only one, named tabersonine derivative 19-O-acetyltransferase (TAT) was able to acetylate the 19-hydroxytabersonine derivatives from roots, such as minovincinine and hörhammericine, following expression in yeast. Kinetic studies also showed that the recombinant TAT was specific for root MIAs and displayed an up to 200-fold higher catalytic efficiency than MAT. In addition, gene expression analysis, protein subcellular localization and heterologous expression in Nicotiana benthamiana were in agreement with the prominent role of TAT in acetylation of root-specific MIAs, thereby redefining the molecular determinants of the root MIA biosynthetic pathway. Finally, identification of TAT provided a convenient tool for metabolic engineering of MIAs in yeast enabling efficiently mixing different biosynthetic modules spatially separated in the whole plant. This combinatorial synthesis associating several enzymes from Catharanthus roseus resulted in the conversion of tabersonine in tailor-made MIAs bearing both leaf and root-type decorations.

Grape canes represent a promising source of bioactive phytochemicals. However the stabilization of the raw material after pruning remains challenging. We recently reported the induction of stilbenoid metabolism after winter pruning including a strong accumulation of E-resveratrol and E-piceatannol during the first six weeks of storage. In the present study, the effect of mechanical wounding on freshly-pruned canes was tested to increase the induction of stilbenoid metabolism. Cutting the grape canes in short segments immediately after pruning triggered a transient expression of phenylalanine ammonia-lyase (PAL) and stilbene synthase (STS) genes, followed by a rapid accumulation of E-resveratrol and E-piceatannol. The degree of stilbenoid induction was related to the intensity of mechanical wounding. Data suggest that a global defense response is triggered involving jasmonate signaling, PR proteins and stilbenoid metabolism. Mechanical wounding of freshly-pruned canes drastically shortens the time required to reach maximal stilbenoid accumulation from 6 to 2weeks.

L’arsenal thérapeutique anti-thrombotique, en constante évolution, regroupe de nombreuses molécules permettant d’assurer au patient une protection efficace face au risque thromboembolique. Cependant, le maniement de ces composés reste complexe en cas d’intervention chirurgicale et notamment dans le domaine de l’odontostomatologie. L’arrêt, même temporaire, de ces traitements pour privilégier la réussite de l’hémostase augmente le risque d’évènements thromboemboliques. A l’inverse, le maintien de ces thérapies majore de façon significative la survenue d’accidents hémorragiques. L’ensemble des études cliniques ont permis aux différentes sociétés scientifiques d’établir des protocoles de prise en charge standardisés assurant une sécurité chirurgicale optimale pour les patients.Ces choix thérapeutiques évaluent sans cesse le rapport bénéfice/risque dans la plupart des situations cliniques rencontrées par les différents professionnels de santé. Le pharmacien d’officine, véritable lien entre le malade, le chirurgien-dentiste et le médecin, détient un rôle essentiel auprès du patient en étant capable de le rassurer, de le conseiller ainsi qu’en lui prodiguant des conseils adaptés vis-à-vis des modifications de son traitement anti-thrombotique en vue de la réalisation d’une intervention chirurgicale bucco-dentaire.

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Introduction: the internship in emergency service can be of a considerable educational contribution provided a seniority of quality. However, several factors hinder this seniorization and tutoring would allow seniors to play its dual role of supervision and clinical teaching. We sought to investigate the correlation between self-assessment and hetero-assessment of internal autonomy. Material and method: this monolingual observational prospective study was carried out in the adult emergency department of the Pellegrin Hospital of the Bordeaux University Hospital from November 2nd, 2016 to October 31st, 2017. A self-evaluation questionnaire was provided by each of the interns at the hospital. beginning of the internship (M0), mid-stage (M3) and end of internship (M6). Each intern was assigned one or two tutors from the service seniors who completed a M3 and M6 hetero-evaluation questionnaire. Results: we did not demonstrate a significant correlation between self and hetero evaluation of internal autonomy in the middle of the semester (Coef: 0.217-IC 95% [-0.16, 0.54]) and at the end of the semester (Coef: 0.036-IC 95% [-0.33, 0.39]). We isolated several determinants of autonomy: patient flow management (0.215-IC 95% [0.02; 0.41]), performing technical procedures (0.25-IC 95% [0.15; 35] and the timing of the internship, namely M3 (-0.56-IC 95% [-1.02; -0.10]) and M6 (0.78-IC 95% [0.45, 1.10]). observed a change in skills felt by the intern not statistically significant on some items in the second part of the course Discussion: the lack of significant correlation highlights a lack of common work and also the existence of a margin of progress Regarding the quality of seniorization, in terms of involvement, this work will help to set up a genuine tutor / internal relationship, which will require better correlation of schedules and training of tutors in supervision techniques. encourage more regular interviews Learning should be targeted with training technical gestures and flow management through different teaching methods such as role play and simulation on manikin. This learning will have to spread throughout the semester in order to avoid a stagnation of the progression of the internal mid-term., Introduction : le stage en service d’urgence peut être d’un apport considérable pédagogique à condition d’une séniorisation de qualité. Cependant, plusieurs facteurs contrarient cette séniorisation et le tutorat permettrait aux séniors de jouer son double rôle de supervision et d’enseignement clinique. Nous avons cherché à étudier la corrélation entre l’auto-évaluation et hétéro-évaluation de l’autonomie de l’interne. Matériel et méthode : cette étude prospective observationnelle mono centrique a été réalisé dans le service des urgences adultes de l’hôpital Pellegrin du CHU de Bordeaux du 02 Novembre 2016 au 31 Octobre 2017. Un questionnaire d’auto évaluation était renseigné par chacun des internes au début du stage (M0), à mi-stage (M3) et en fin de stage (M6). Chaque interne se voyait attribuer un ou deux tuteurs parmi les séniors du service qui renseignaient un questionnaire d’hétéro-évaluation à M3 et M6. Résultats : nous n’avons pas démontré de corrélation significative entre auto et hétéro évaluation de l’autonomie de l’interne que ce soit en milieu de semestre (Coef : 0,217-IC 95% [-0,16;0,54]) et en fin de semestre (Coef : 0,036-IC 95% [-0,33 ;0,39]). Nous avons isolé plusieurs déterminants de l’autonomie : la gestion du flux de patient (0,215-IC 95% [0,02;0,41]), la réalisation des gestes techniques (0,25-IC 95% [0,15 ;0,35] et le moment du stage, à savoir M3 (-0,56-IC 95%[ -1,02 ;-0,10]) et M6 (0,78-IC 95% [0,45 ;1,10]).Nous avons observé une évolution des compétences ressentie par l’interne non statistiquement significative sur certains items dans la deuxième partie du stage. Discussion: l’absence de de corrélation significative souligne un manque de travail commun et également l’existence d’une marge de progression concernant la qualité de la séniorisation. En termes d’implication, ce travail aidera à mettre en place une véritable relation tuteur/interne. Cela passera par une meilleure corrélation des plannings et une formation des tuteurs aux techniques de supervision. Il apparait essentiel également de favoriser des entretiens plus réguliers. L’apprentissage devra être ciblé avec une formation aux gestes technique et à la gestion du flux par des méthodes pédagogiques différentes tels que le jeu de rôle et la simulation sur mannequin. Cet apprentissage devra s’étaler tout au long du semestre afin d’éviter une stagnation de la progression de l’interne à mi semestre.