Search

La médecine générale (MG) est une discipline avec des contenus spécifiques de formation, de recherche et de pratique clinique. Elle se caractérise par son contexte de soins premiers et des fondements scientifiques internationalement reconnus. Une liste des familles de situations prévalentes et le référentiel des compétences ont été publiés et fondent les choix de formation. Le portfolio est un des outils adéquats décrits dans la littérature pour évaluer le niveau de compétence. Il contient différents travaux d’écriture et les réflexions critiques à propos de situations cliniques rencontrées, formalisant l’apprentissage qui en a été retiré1...

Description, FGF and Wnt signaling controls the phase transition of the ocular fate., The developing vertebrate eye cup is partitioned into the neural retina (NR), the retinal pigmented epithelium (RPE), and the ciliary margin (CM). By single-cell analysis, we showed that fibroblast growth factor (FGF) signaling regulates the CM in its stem cell–like property of self-renewal, differentiation, and survival, which is balanced by an evolutionarily conserved Wnt signaling gradient. FGF promotes Wnt signaling in the CM by stabilizing β-catenin in a GSK3β-independent manner. While Wnt signaling converts the NR to either the CM or the RPE depending on FGF signaling, FGF transforms the RPE to the NR or CM dependent on Wnt activity. The default fate of the eye cup is the NR, but synergistic FGF and Wnt signaling promotes CM formation both in vivo and in human retinal organoid. Our study reveals that the vertebrate eye develops through phase transition determined by a combinatorial code of FGF and Wnt signaling.

The prevalence of radiation-induced nausea and vomiting varies between 40% and 80%. They have many consequences on treatment and comorbidities. This work thus aimed to define clinical practice guidelines for the management of radiation-induced nausea and vomiting.XXXXX, XXXX, XXX, XXXXX, XXXX and XXXX compiled a working group who draft these recommendations.The assessment of the emetogenic risk found two main predictive factors: 1) the irradiated anatomical location, 2) an associated concomitant chemotherapy. In the case of exclusive radiotherapy, primary antiemetic prophylaxis depends on the emetogenic risk (the irradiated anatomical location). In the case of concomitant chemotherapy, the emetogenic risk is generally higher and the primary antiemetic prophylaxis corresponds to that of chemotherapy-induced nausea and vomiting. In cases where symptoms persist, remedial treatments are poorly codified.Radiation-induced nausea and vomiting remains underdiagnosed and undertreated, its rapid detection and treatment are essential to reinstate good clinical practice.

The developing vertebrate eye cup is partitioned into the neural retina (NR), the retinal pigmented epithelium (RPE) and the ciliary margin (CM). By single cell analysis, we showed that a gradient of FGF signaling regulates demarcation and subdivision of the CM and controls its stem cell-like property of self-renewal, differentiation and survival. This regulation by FGF is balanced by an evolutionarily conserved Wnt signaling gradient induced by the lens ectoderm and the periocular mesenchyme, which specifies the CM and the distal RPE. These two morphogen gradients converge in the CM where FGF signaling promotes Wnt signaling by stabilizing β-catenin in a GSK3β-independent manner. We further showed that activation of Wnt signaling converts the NR to either the CM or the RPE depending on the level of FGF signaling. Conversely, activation of FGF transforms the RPE to the NR or CM dependent on Wnt activity. We demonstrated that the default fate of the eye cup is the NR, but synergistic FGF and Wnt signaling promotes CM formation both in vivo and in retinal organoid culture of human iPS cells. Our study reveals that the vertebrate eye develops through phase transition determined by a combinatorial code of FGF and Wnt signaling.

Resume Position du probleme Le reperage des patients ayant une consommation d’alcool a risque, c’est-a-dire superieure aux seuils definis par les autorites de sante ou associee a une situation particuliere (prise de psychotropes, pathologie organique, conduite de vehicule, grossesse), represente un enjeu important en soins premiers. Peu d’etudes sur le point de vue des patients a ce sujet ont ete realisees. L’objectif principal de notre etude etait de decrire ce que rapportent les patients des pratiques de reperage de la consommation d’alcool a risque par leur medecin generaliste. L’objectif secondaire etait d’identifier les facteurs associes a la connaissance de la consommation d’alcool des patients par leur medecin generaliste. Methodes Une etude observationnelle transversale a ete menee dans neuf centres investigateurs ambulatoires pendant six mois. Les patients majeurs devaient remplir un questionnaire confidentiel en aveugle de leur medecin, renseignant leur niveau de consommation d’alcool et leur perception des pratiques de reperage de leur praticien a ce sujet. Des analyses descriptives, univariees et multivariees de regression logistique ont ete realisees. Resultats Au total, 445 patients ont ete inclus dans l’etude parmi lesquels 62 usagers d’alcool a risque (13,9 %). La majorite des patients declaraient que leur medecin generaliste ne leur posait pas de questions sur la consommation d’alcool lors des premieres consultations (86,1 %) ni au cours du temps (83,3 %). Seuls 4,2 % des patients avaient deja parle d’eux-memes d’alcool a leur praticien. Les patients n’avaient pas honte de parler d’alcool (99,2 %) et trouvaient leur medecin competent dans ce domaine (100 %). En analyse multivariee, les facteurs independamment associes a la connaissance de la consommation d’alcool du moment du patient par le medecin generaliste etaient le questionnement par ce dernier a ce sujet lors des premieres consultations (p Conclusion Le reperage de la consommation d’alcool a risque est peu effectue par le medecin generaliste, une minorite de patients pensant que leur praticien connaissait leur consommation. Il pourrait etre ameliore en etant systematique lors des premieres consultations et planifie regulierement par la suite, notamment en cas de situations a risque.

The cortex projects to the dorsal striatum topographically1,2 to regulate behaviour3-5, but spiking activity in the two structures has previously been reported to have markedly different relations to sensorimotor events6-9. Here we show that the relationship between activity in the cortex and striatum is spatiotemporally precise, topographic, causal and invariant to behaviour. We simultaneously recorded activity across large regions of the cortex and across the width of the dorsal striatum in mice that performed a visually guided task. Striatal activity followed a mediolateral gradient in which behavioural correlates progressed from visual cue to response movement to reward licking. The summed activity in each part of the striatum closely and specifically mirrored activity in topographically associated cortical regions, regardless of task engagement. This relationship held for medium spiny neurons and fast-spiking interneurons, whereas the activity of tonically active neurons differed from cortical activity with stereotypical responses to sensory or reward events. Inactivation of the visual cortex abolished striatal responses to visual stimuli, supporting a causal role of cortical inputs in driving the striatum. Striatal visual responses were larger in trained mice than untrained mice, with no corresponding change in overall activity in the visual cortex. Striatal activity therefore reflects a consistent, causal and scalable topographical mapping of cortical activity.

The screening of patients who are at-risk drinkers, which means exceeding the thresholds defined by health authorities or associated with a specific situation (taking psychotropic drugs, having an organic pathology, driving a vehicle, drinking during pregnancy), represents a major issue in primary care. Few studies have offered perspective from the patients' standpoint. The main purpose of this study was to describe general practitioners at-risk drinking screening from their patients point of view. The secondary objective was to identify the factors associated with perception of satisfactory general practitioner knowledge about alcohol consumption.A quantitative cross-sectional study was launched in 9 general practitioner offices over 6 months. Patients older than 18 were recruited to answer a questionnaire blinded from their general practitioner, indicating the level of their alcohol consumption and their perception regarding their general practitioner's screening methods. Descriptive, univariate and multivariate logistic regression analyses were performed.All in all, 445 patients were analyzed. Sixty-two at-risk drinkers were screened (13.9 %). Most of the patients declared they had not been interviewed about their alcohol consumption by their general practitioner either during initial consultations (86.1 %) or over time (83.3 %). Only 4.2 % of patients had previously initiated discussion about their consumption. Patients were not ashamed to talk about alcohol (99.2 %) and found their general practitioner to be competent on this topic (100 %). In multivariate analysis, independent factors associated with a good general practitioner knowledge about their patients' current consumption were the questions put forward by their general practitioner about alcohol consumption during their first visit (P0.001) and during subsequent visits (P0.001).This study showed a low general practitioner screening rate of their patients' at-risk drinking. Only a minority of patients, including at-risk drinkers, declared that their general practitioner was aware of their level of alcohol consumption. Screening could be improved by being systematized during initial consultations and regularly scheduled during subsequent visits, especially in at-risk situations.

Retinal ganglion cells (RGC), together with cone photoreceptors, horizontal cells (HC) and amacrine cells (AC), are the first classes of neurons produced in the retina. Here we have profiled 5348 single retinal cells and provided a comprehensive transcriptomic atlas showing the broad diversity of the developing retina at the time when the four early-born cells are being produced. Our results show the transcriptional sequences that establish the hierarchical ordering of early cell fate specification in the retina. RGC maturation follows six waves of gene expression, giving new insight into the regulatory logic of RGC differentiation. Early-generated RGCs transcribe an increasing amount of guidance cues for young peripheral RGC axons that express the matching receptors. Finally, spatial signatures in sub-populations of RGCs allowed to define novel molecular markers that are spatially restricted during the development of the retina. Altogether this study is a valuable resource that identifies new players in mouse retinal development, shedding light on transcription factors sequence and guidance cues dynamics in space and time.

Estrogen receptors (ER) are used as therapeutic targets, either for contraception or for the hormonal replacement therapy in menopausal women, but also in physiopathology for breast cancer treatment. It is therefore important to understand the tissue-specificity of the actions of ERα to optimize the benefits/risks ratio in each tissue. Besides the conventional nuclear ERα acting as a transcription factor, many studies have demonstrated that ERα is also able to mediate extra nuclear signaling, enabling rapid actions of estrogen. Recently, new transgenic mouse models were used to study these effects, and allowed to genetically segregate membrane versus nuclear actions of a steroid hormone receptor, demonstrating their in vivo tissue-specific roles.

Au Mali, l’usage des pesticides sur la culture de coton constitue un réel problème de santé publique et pour l’environnement. Cette étude porte sur les risques potentiels correspondant à la « dangerosité » des matières actives présentes dans les pesticides distribués pour le coton. Nous avons recensé 174 pesticides homologués par le Comité sahélien des pesticides (CSP) destinés à la culture du coton, dont 106 insecticides et fongicides et 68 herbicides. Ils sont formulés à partir de 50 matières actives ; 10 sont interdites en Europe et se retrouvent dans 35 produits homologués (soit 20 % des produits disponibles). Un indice de risque de toxicité (IRT) sur la santé des utilisateurs a été calculé pour chacune des 50 matières actives tenant compte de leurs toxicités aiguë et chronique. Il montre que la pendiméthaline et la bifenthrine ont les IRT les plus élevés respectivement pour les herbicides et les insecticides. Un indicateur de contamination des sols et des eaux de surface et souterraine par ces matières actives a été calculé. Il montre qu’une matière active peut présenter un risque important pour la santé et avoir un fort niveau de toxicité pour l’environnement ou avoir un faible impact sur la santé mais présenter un risque élevé pour l’environnement. Une sensibilisation des différents acteurs sur les risques encourus par les pesticides permettrait de réduire leurs impacts sur la santé humaine et l’environnement.

A global analysis of gene expression during development reveals specific transcription patterns associated with the emergence of various cell types, tissues and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hoxd genes is differentially controlled in space and time in cells that will pattern the digits and the arms. Here we analyze single-cell transcriptomes of limb bud cells and show that Hox genes are expressed in specific combinations that match particular cell types. In the presumptive digits, we find that the expression of Hoxd gene is unbalanced, despite their common genomic proximity to known global enhancers, often expressing only a subset of the five genes transcribed in these cells. We also report that combinatorial expression follows a pseudo-time sequence, suggesting that a progression in combinatorial expression may be associated with cellular diversity in developing digits.

International audience; Faced with health, environmental, and socio-economic issues related to the heavy use of pesticides, diffuse phytosanitary pollution becomes a major concern shared by all the field actors. These actors, namely the farmers and territorial managers, have expressed the need to implement decision support tools for the territorial management of diffuse pollution resulting from the plant protection practices and their impacts. To meet these steadily increasing requests, a cartographic analysis approach was implemented based on GIS which allows the spatialization of the diffuse pollution impacts related to plant protection practices on the Etang de l’Or catchment area in the South of France. Risk mapping represents a support-decision tool that enables the different field actors to identify and locate vulnerable areas, so as to determine action plans and agri-environmental measures depending on the context of the natural environment. This work shows that mapping is helpful for managing risks related to the use of pesticides in agriculture by employing indicators of pressure (TFI) and risk on the applicator’s health (IRSA) and on the environment (IRTE). These indicators were designed to assess the impact of plant protection practices at various spatial scales (field, farm, etc.). The cartographic analysis of risks related to plant protection practices shows that diffuse pollution is unequally located in the North (known for its abundant garrigues and vineyards) and in the South of the Etang de l’Or catchment area (the Mauguio-Lunel agricultural plain known for its diversified cropping systems). This spatial inequity is essentially related to land use and agricultural production system. Indeed, the agricultural lands cover about 60% of the total catchment area. Consequently, this cartographic analysis helps the territorial actors with the implementation of strategies for managing risks of diffuse pollution related to pesticides use in agriculture, based on environmental and socio-economic issues and the characteristics of the natural environment.

BackgroundThe transcriptional activation of Hoxd genes during mammalian limb development involves dynamic interactions with the two Topologically Associating Domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior Hoxd genes in developing digits is controlled by regulatory elements located in the centromeric TAD (C-DOM) through long-range contacts. To assess the structure-function relationships underlying such interactions, we measured compaction levels and TAD discreteness using a combination of chromosome conformation capture (4C-seq) and DNA FISH.ResultsWe challenged the robustness of the TAD architecture by using a series of genomic deletions and inversions that impact the integrity of this chromatin domain and that remodel the long-range contacts. We report multi-partite associations between Hoxd genes and up to three enhancers and show that breaking the native chromatin topology leads to the remodelling of TAD structure.ConclusionsOur results reveal that the re-composition of TADs architectures after severe genomic re-arrangements depends on a boundary-selection mechanism that uses CTCF-mediated gating of long-range contacts in combination with genomic distance and, to a certain extent, sequence specificity.

Background The transcriptional activation of HoxD genes during mammalian limb development involves dynamic interactions with two topologically associating domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior HoxD genes in developing digits is controlled by regulatory elements located in the centromeric TAD (C-DOM) through long-range contacts. Results To assess the structure–function relationships underlying such interactions, we measured compaction levels and TAD discreteness using a combination of chromosome conformation capture (4C-seq) and DNA FISH. We assessed the robustness of the TAD architecture by using a series of genomic deletions and inversions that impact the integrity of this chromatin domain and that remodel long-range contacts. We report multi-partite associations between HoxD genes and up to three enhancers. We find that the loss of native chromatin topology leads to the remodeling of TAD structure following distinct parameters. Conclusions Our results reveal that the recomposition of TAD architectures after large genomic re-arrangements is dependent on a boundary-selection mechanism in which CTCF mediates the gating of long-range contacts in combination with genomic distance and sequence specificity. Accordingly, the building of a recomposed TAD at this locus depends on distinct functional and constitutive parameters. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1278-z) contains supplementary material, which is available to authorized users.

International audience; The health, environmental and socio-economic issues related to the massive use of plant protection products are a concern for all the stakeholders involved in the agricultural sector. These stakeholders, including farmers and territorial actors, have expressed a need for decision-support tools for the management of diffuse pollution related to plant protection practices and their impacts. To meet the needs expressed by the public authorities and the territorial actors for such decision-support tools, we have developed a technical-economic model “OptiPhy” for risk mitigation based on indicators of pesticide toxicity risk to applicator health (IRSA) and to the environment (IRTE), under the constraint of suitable economic outcomes. This technical-economic optimisation model is based on linear programming techniques and offers various scenarios to help the different actors in choosing plant protection products, depending on their different levels of constraints and aspirations. The health and environmental risk indicators can be broken down into sub-indicators so that management can be tailored to the context. This model for technical-economic optimisation and management of plant protection practices can analyse scenarios for the reduction of pesticide-related risks by proposing combinations of substitution PPPs, according to criteria of efficiency, economic performance and vulnerability of the natural environment. The results of the scenarios obtained on real ITKs in different cropping systems show that it is possible to reduce the PPP pressure (TFI) and reduce toxicity risks to applicator health (IRSA) and to the environment (IRTE) by up to approximately 50 %.

Objectif de l’etude Evaluation d’une serie retrospective de patients traites consecutivement avec modulation d’intensite volumetrique (VMAT) pour un carcinome epidermoide du canal anal. Materiel et methode Entre 2012 et 2017, 47 patients ont ete consecutivement traites pour un carcinome epidermoide du canal anal localement evolue. L’âge moyen etait de 64,5 ans, pour 29 femmes (61,7 %) et 18 hommes (38,3 %). Il y avait un cancer de stade I (2,1 %), 16 de stade II (34 %), 12 de stade IIIa (25,5 %) et 18 de stade IIIb (38,3 %). La dose prescrite dans la tumeur initiale et le pelvis incluant les aires inguinales etait de 46 Gy en 23 fractions chez huit patients, 50 Gy en 25 fractions chez une patiente et 45 Gy en 28 fractions chez 38 patients. Un complement d’irradiation dans le niveau tumoral et les adenopathies atteintes a ete prescrit sans intervalle libre a hauteur de 20 Gy en dix fractions chez neuf patients, de 16 Gy en huit fractions chez 36 patients et de 15 Gy en huit fractions chez un. Une chimiotherapie concomitante par 5-fluoro-uracile et mitomycine C a ete administree a 76,6 % des patients, un patient (2,1 %) ayant recu l’association de 5-fluoro-uracile et de cisplatine, un autre l’association de 5-fluoro-uracile et de carboplatine. La toxicite precoce et tardive a ete cotee selon les Common Terminology Criteria for Adverse Events version 3.0 et l’analyse des taux de survie calculee selon la methode Kaplan–Meier. Resultats Le suivi median etait de 39,7 mois (3,1–73,9). Les probabilites de survie globale, sans progression et sans colostomie a 2 et 4 ans etaient respectivement de 88,2 % [85,8–98,8] et 76,4 % [58,1–-88,3], 87,2 % [73,1–94,4] et 80,9 % [62–91,7], 78,6 % [63,7–88,4] et 70,1 % [52,8–83,1]. La toxicite precoce de grade 3 ou plus etait dermatologique (29,8 %), urologique (2,1 %), digestive (23,4 %, dont une de grade 5) et hematologique (12,8 %, dont quatre neutropenies febriles, soit 10,6 %). La toxicite tardive etait digestive (de grade 3, une sur 30 et grade 2, une sur 30) et sphincteriennes (de grade 4, deux sur 30 [colostomies] et grade 2, deux sur 30). Conclusion La prise en charge du cancer du carcinome epidermoide du canal anal par l’arctherapie volumetrique modulee permet un taux de controle tumoral comparable aux etudes publiees. La prevention et la prise en charge de la toxicite est essentielle.

Reference EPFL-CONF-219859View record in Web of Science Record created on 2016-07-19, modified on 2017-03-26

Transcription of HoxD cluster genes in limbs is coordinated by two topologically associating domains (TADs), neighboring the cluster and containing various enhancers. Here, we use a combination of microscopy approaches and chromosome conformation capture to assess the structural changes occurring in this global architecture in various functional states. We observed that despite their spatial juxtaposition, the TADs are consistently kept as distinct three-dimensional units. Hox genes located at their boundary can show significant spatial segregation over long distances, suggesting that physical elongation of the HoxD cluster occurs. The use of superresolution imaging (STORM [stochastic optical reconstruction microscopy]) revealed that the gene cluster can be in an either compact or elongated shape. The latter configuration is observed in transcriptionally active tissue and in embryonic stem cells, consistent with chromosome conformation capture results. Such morphological changes at HoxD in developing digits seem to be associated with its position at the boundary between two TADs and support the idea that chromatin dynamics is important in the establishment of transcriptional activity.

SummaryGrowing axons are guided to their targets by attractive and repulsive cues. In the developing spinal cord, Netrin-1 and Shh guide commissural axons toward the midline. However, the combined inhibition of their activity in commissural axon turning assays does not completely abrogate turning toward floor plate tissue, suggesting that additional guidance cues are present. Here we show that the prototypic angiogenic factor VEGF is secreted by the floor plate and is a chemoattractant for commissural axons in vitro and in vivo. Inactivation of Vegf in the floor plate or of its receptor Flk1 in commissural neurons causes axon guidance defects, whereas Flk1 blockade inhibits turning of axons to VEGF in vitro. Similar to Shh and Netrin-1, VEGF-mediated commissural axon guidance requires the activity of Src family kinases. Our results identify VEGF and Flk1 as a novel ligand/receptor pair controlling commissural axon guidance.

Resume Objectifs Le syndrome lipodystrophique du patient infecte par le VIH et la dyslipidemie qui l’accompagne sont ameliores par un reentrainement cible au premier seuil ventilatoire (Sv1), mais chez ces patients la signification metabolique de ce Sv1 n’est pas evidente. Nous avons tente de determiner les liens entre ce Sv1 et la calorimetrie d’effort et d’etudier les effets d’un reentrainement cible au niveau maximal d’oxydation des lipides (Lipoxmax) determine par cette derniere technique, sur ce tableau metabolique. Methodes Vingt et un sujets (trois femmes, 18 hommes, âge : 46,05 ± 1,7 ans, taille : 1,72 ± 0,02 m ; poids : 69,10 ± 2,47 kg), stables sur le plan immmunologique et therapeutique, ont beneficie d’une evaluation anthropometrique (impedancemetrie, coupe tomodensitometrique L4/L5), biologique et de l’aptitude physique au cours d’un test d’effort maximal avec determination des seuils ventilatoires et une calorimetrie indirecte d’effort pour mesurer l’oxydation des lipides et des glucides au cours de quatre paliers sous-maximaux de six minutes. Sur la base de ce dernier test dix sujets ont ete reentraines un an et retestes a l’issue de cette periode. Resultats Le point de croisement (PCX) definissant le niveau de passage a une utilisation majoritaire des glucides est abaisse a 43,47 ± 5,9 watts, soit 32,29 ± 4,4 watts en moyenne au dessous du Sv1 situe a 76,33 ± 5,5 watts. Le Lipoxmax est situe a 49,59 ± 4,53 watts. Si le Sv1 et le PCX sont bien correles (r = R = 0,762 ; p V O 2 max qui passe de 26,49 ± 1,36 a 31,13 ± 1,70 (p Discussion et conclusions Chez le HIV lipodystrophique, la calorimetrie d’effort montre une tendance a utiliser majoritairement, de facon precoce, les glucides, et le PCX semble etroitement lie au profil lipidique sanguin. Contrairement a la population generale, le seuil ventilatoire, dont l’interet en reentrainement a ete montre, ne coincide pas chez ces sujets avec le PCX. Le reentrainement en endurance cible par la calorimetrie d’effort semble avoir des effets analogues a ceux du reentrainement cible au Sv1 et notamment ameliorer nettement le bilan lipidique.

International audience

International audience; Embryogenesis requires the precise activation and repression of many transcriptional regulators. The Polycomb group proteins and the associated H3K27me3 histone mark are essential to maintain the inactive state of many of these genes. Mammalian Hox genes are targets of Polycomb proteins and form local 3D clusters centered on the H3K27me3 mark. More distal contacts have also been described, yet their selectivity, dynamics, and relation to other layers of chromatin organization remained elusive. We report that repressed Hox genes form mutual intra- and interchromosomal interactions with other genes located in strong domains labeled by H3K27me3. These interactions occur in a central and active nuclear environment that consists of the HiC compartment A, away from peripheral lamina-associated domains. Interactions are independent of nearby H3K27me3-marked loci and determined by chromosomal distance and cell-type-specific scaling factors, thus inducing a moderate reorganization during embryogenesis. These results provide a simplified view of nuclear organization whereby Polycomb proteins may have evolved to repress genes located in gene-dense regions whose position is restricted to central, active, nuclear environments.

Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation of Hoxd genes during vertebrate digit development involves modifications in 3D interactions within and around the HoxD gene cluster. This reorganization follows a global transition from one set of regulatory contacts to another, between two topologically associating domains (TADs) located on either side of the HoxD locus. Here, we use 3D DNA FISH to assess the spatial organization of chromatin at and around the HoxD gene cluster and report that although the two TADs are tightly associated, they appear as spatially distinct units. We measured the relative position of genes within the cluster and found that they segregate over long distances, suggesting that a physical elongation of the HoxD cluster can occur. We analyzed this possibility by super-resolution imaging (STORM) and found that tissues with distinct transcriptional activity exhibit differing degrees of elongation. We also observed that the morphological change of the HoxD cluster in developing digits is associated with its position at the boundary between the two TADs. Such variations in the fine-scale architecture of the gene cluster suggest causal links among its spatial configuration, transcriptional activation, and the flanking chromatin context.

A numerical method based on a boundary element method (BEM) has been developed for computing the velocity and the shape of long bubbles moving steadily in stagnant and flowing liquid in 2D case: plane and axisymmetrical. The flow is assumed to be inviscid and incompressible. The method consists in solving simultaneously a Poisson equation characterizing the flow and an equation for bubble shape in the form of a functional-differential equation resulting from both Bernoulli equation and the jump conditions at the interface. The Poisson equation is solved by a BEM with an iterative loop for nonlinear source term while the system of nonlinear algebraic equations obtained by discretizing the equation on the interface is solved by the Powell's hybrid algorithm. The bubble shape and velocity are obtained as a part of the solution. The problem of multiple solutions is investigated numerically and the maximum velocity criterion is used for selecting the physical solution. The results obtained by the simulation are in good agreement with the experimental and numerical results of previous studies.

The aim of this study was to assess the balance between water demand and availability and its spatial and temporal variability from 1971 to 2009 in the Herault (2500 km2, France) and the Ebro (85 000 km2, Spain) catchments. Natural streamflow was evaluated using a conceptual hydrological model. The regulation of river flow was accounted for through a widely applicable demand-driven reservoir management model applied to the largest dam in the Herault basin and to 11 major dams in the Ebro basin. Urban water demand was estimated from population and monthly unit water consumption data. Water demand for irrigation was computed from irrigated area, crop and soil data, and climatic forcing. Finally, a series of indicators comparing water supply and water demand at strategic resource and demand nodes were computed at a 10 day time step. Variations in water stress in each catchment over the past 40 years were successfully modeled, taking into account climatic and anthropogenic pressures and changes in water management strategies over time. Observed changes in discharge were explained by separating human and hydro-climatic pressures on water resources: respectively 20 and 3% of the decrease in the Ebro and the Herault discharges were linked to human-induced changes. Although key areas of the Herault basin were shown to be highly sensitive to hydro-climatic variability, the balance between water uses and availability in the Ebro basin appears to be more critical, owing to high agricultural pressure on water resources. The proposed modeling framework is currently being used to assess water stress under climatic and socio-economic prospective scenarios. Further research will investigate the effectiveness of adaptation policies aimed at maintaining the balance between water use and availability.

Introduction Les intoxications par les substances psychoactives (SPA) sont de plus en plus nombreuses en Europe et concernent majoritairement les patients jeunes. De nombreux nouveaux produits de synthese (NPS) vendus via l’Internet sont consommes notamment en contexte festif ; leur toxicite est mal connue. Les centres d’addictovigilance et antipoison sont regulierement sollicites pour des intoxications graves aboutissant a des hospitalisations pour lesquelles les preuves analytiques sont souvent manquantes compliquant la prise en charge. Les objectifs de cette etude sont d’identifier les principales SPA en lien avec les tableaux cliniques les plus graves, pour en ameliorer la prise en charge ulterieure. Materiel et methodes Etude prospective conduite au cours de deux feria (ete 2015). Tout patient admis a un poste medical avance avec des troubles neurologiques et/ou du comportement evocateur d’une prise de SPA et/ou rapportant avoir consomme des SPA etait inclus. Un examen clinique, une mesure de la glycemie capillaire au doigt etaient realises, et si possible, un recueil des urines et un prelevement de cheveux. Une goutte de sang capillaire etait egalement depose sur un papier buvard ( dried blood spot [DBS]) et adresse au laboratoire pour analyse. Resultats Vingt-sept patients, principalement des hommes, ont ete inclus : 27 DBS, 24 prelevements de cheveux et 14 prelevements urinaires ; 85 % des patients avaient entre 15 et 30 ans Les signes etaient majoritairement neurologiques ; 4 patients presentaient un syndrome serotoninergique incomplet. Aucun deces, ni admission en reanimation n’ont ete observes. Cocaine, psilocine et de nombreux medicaments psychotropes ont ete identifies mais aucun NPS. Les analyses de cheveux ont permis le plus souvent d’etayer une chronicite des consommations et de mettre en evidence du 5-EAPB et de la methylone dans 1 cas. Discussion Il s’agit d’une etude preliminaire avec un effectif limite. Les tableaux cliniques etaient generalement coherents avec les SPA identifiees. Aucun NPS n’a ete identifie. Les personnes frequentant les feria sont differentes de celles frequentant les festivals de musique, ce qui peut expliquer l’absence de NPS : la realisation d’une etude similaire dans les festivals de musique devrait etre pertinente en ce sens.

A bubbly flow experiment has been performed in a horizontal channel in order to simulate the dynamical effects of the nucleation of bubbles and their departure from the wall in boiling flows. Bubbles were injected through a porous plate located on the lower wall. The void fraction, bubble velocity and diameter were measured with a fibre-optic probe and the liquid flow in the bubble layer was studied with a hot film anemometer. The void fraction profiles are nearly self-similar. The expansion of the bubble layer is quasi-linear with the distance downstream, with a rate of expansion depending on the bubble diameter. Comparison with a simple model of bubble trajectories highlights the role of the lift force in the development of the bubble layer. The mean velocity in the bubble layer does not differ greatly from that measured in single-phase flow, except near the wall. The velocity profiles follow a logarithmic law similar to that for turbulent flow over a rough surface suggesting that bubbles attached to the wall act as roughness elements on the liquid flow. The turbulent kinetic energy is greater than in single-phase flow. The additional turbulence is analysed and attributed partly to the relative motion of the bubbles and partly to the augmentation of the turbulent shear stress in the bubble layer.

International audience; Diffuse phytosanitary pollution is a complex phenomenon to manage. Reducing this type of pollution is one of today’s key socio-economic and environmental challenges. At the regional level, few approaches enable the actors concerned to implement agricultural management strategies to reduce the use and impact of phytosanitary products. Our research problem focused on the consequences of intensive agriculture and, in particular, how to evaluate the impact of phytosanitary products on human health and the environment. In this article, we present the SimPhy simulation game which places the actors from a given region directly into a situation in which they manage farms whilst under pressure to reduce phytosanitaries (quantity and toxicity). The application focused on the Merja Zerga catchment area in Morocco. The region is dominated by intensive agriculture which is located upstream from a Ramsar-classified wetland area. The SimPhy simulation game is based on a decision support system-type tool. It allows us to anticipate the impact of regulations on farming systems. It also enables us to analyse the consequences of the actors’ strategies on farm economies, human health and the quality of ecosystems. Initial results from the SimPhy simulation game enabled the technicians from Agricultural Development Center (CDA) themselves to learn about managing agricultural production systems in a dynamic and interactive fashion. With the simulation game, it was possible to learn about the farmer's ability to adapt to new regulatory constraints, and the involved consequences for toxicity risks for human health and the environment.