Role of superantigenic strains in the prognosis of community-acquired methicillin-susceptible Staphylococcus aureus bacteraemia

ABSTRACTMethicillin-susceptible Staphylococcus aureus (MSSA) strains can produce superantigenic toxins that may trigger a massive release of pro-inflammatory cytokines, which are involved in the onset of septic shock. This 1-year prospective pilot study assessed the role of the production of superantigenic toxins in the outcome of immunocompetent patients hospitalised for community-acquired MSSA bacteraemia. Thirty-seven patients were enrolled, of whom 14 died in hospital. Fourteen patients had septic shock, and the mortality rate in this subgroup was 56%. Twenty-seven (73%) isolates produced at least one superantigenic toxin, but this did not influence the rate of occurrence of septic shock or death

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

La couche limite extrême du Plateau Antarctique et sa représentation dans les modèles de climat

Observation of the Atmospheric Boundary Layers (ABL) above the Antarctic Plateau has revealed the strongest near-surface temperature stratifications on the Earth. A correct parametrization of the very stratified Antarctic ABLs in General Circulation Models (GCM) is critical since they exert a strongcontrol on the continental scale temperature inversion, on the coastal katabatic winds and subsequently on the Southern Hemisphere circulation. The previous Gewex Atmospheric Boundary Layer Studies (GABLS) highlighted that the parametrization of the very stratified, or very stable, ABLs isone of the most critical challenge in the atmospheric modelers community. Indeed, the nature of the mixing processes are not completely understood and the commonly used similarity laws, on which the model’s parametrization are usually based, are no longer valid. The aim of this PhD work is to evaluate and improve the modelling of the ABL over the Antarctic Plateau by the Laboratoire de Météorologie Dynamique-Zoom (LMDZ) GCM, the atmospheric component of the IPSL Earth System Model in preparation for the sixth Coupled Models Intercomparison Project. Before the model evaluation itself, an in-depth study of the dynamics of the atmospheric surface layer and of the stable ABL over the Antarctic Plateau was carried out from in situ measurements at Dome C. The analysis enabled the first estimations of the roughness length and of the surface fluxes during the polar night at this location as well as the characterization of very frequent occurences of near-surface moisture supersaturations with respect to ice. Investigation of meteorological measure-ments along a 45 m tower also revealed two distinct dynamical regimes of the stable ABL at this location. In particular, the relation between the near surface inversion amplitude and the wind speed takes a typical ’reversed S-shape’, suggesting a system obeing with an hysteresis. A further analysisshowed that this is a clear illustration of a general and robust feature of the stable ABL systems, corresponding to a ‘critical transition’ between a steady turbulent and a steady ‘radiative’ regime. LMDZ was then run on 1D simulations during a typical clear-sky summertime diurnal cycle in the framework of the fourth GABLS case. Sensitivity tests to surface parameters, vertical grid and turbulent mixing parametrizations were performed leading to significant improvements of the model and to a new configuration better adapted for Antarctic conditions. 3D simulations were then carried outwith the ’zooming capability’ of the horizontal grid and with nudging. These simulations enabled a further evaluation of the model over a full year and extending the analysis beyond Dome C. In particular, this study raised the importance of the radiative scheme and of the surface layer scheme forthe modelling of the ABL during the polar night over the Plateau. Finally, the PhD work extented toward the modelling of the stable ABL over the other continents, assessing how the frequently underestimated subgrid mixing of momentum and heat can be compensated by a transfer of large scalekinetic energy toward turbulent kinetic energy when the flow is slowed down by orographic gravity wave drag.L’observation des couches limites atmosphériques au dessus du plateau antarctique a mis en évidence les plus fortes inversions de température proches de la surface de la planète. Bien paramétriser ces couches limites extrêmes dans un modèle de circulation générale est essentiel pour represéntercorrectement l’inversion climatologique de température au dessus du plateau, mais également pour reproduire des vents catabatiques réalistes en aval du plateau et de surcroit, une circulation atmosphérique correcte dans l’hémisphère sud. Les conclusions des précédentes "Gewex AtmosphericBoundary Layer Studies" (GABLS) ont conduit au constat que la paramétrisation des couches limites stables dans les modèles climatiques est une des priorités pour la communauté des modélisateurs.Ceci est dû au fait que la nature même des processus physiques en jeu est mal connue mais aussi parce que les lois de similitudes, sur lesquelles les paramétrisations du mélange turbulent sont fondées, ne sont pas applicables en condition très stable. L’objectif de ces travaux de thèse est d’évaluer et d’améliorer la représentation des couches limites sur le plateau antarctique dans le modèle français de circulation générale Laboratoire de MétéorologieDynamique-Zoom (LMDZ), composante atmosphérique du modèle de climat IPSL. Avant l’évaluation même du modèle, une étude approfondie de la couche limite de surface et de la structure de la couche limite stable a été conduite à partir de l’analyse de mesures in situ au Dôme C. Il en a résulté une caractérisation de la hauteur de rugosité aérodynamique, une estimation des flux turbulents de surface sur une année entière ainsi que la mise en évidence de sursaturations de la vapeur d’eau par rapport à la glace. L’analyse des mesures de température et de vent le long d’une tour de 45 m a aussi montré que la couche limite se comporte tel un système dynamique à deux régimes distincts. La relation entrevitesse du vent et inversion de température décrit un "S renversé", suggérant une transition de régime suivant un hystérésis. Une étude complémentaire a révélé que ce comportement dynamique à deux régimes est une caractéristique générale et robuste des couches limites stables, qui peuvent transiter,selon l’intensité des forçages, d’un régime ’turbulent’ peu stable à un régime ’radiatif’ très stable et vice et versa.Le modèle LMDZ a ensuite été évalué en configuration 1D sur un cycle diurne d’été dans le cadre de la quatrième expérience GABLS. Des tests de sensibilité aux paramètres de surface et à la paramétrisation du mélange turbulent ont été réalisés. Ils ont conduit à de nettes améliorations des performancesdu modèle ainsi qu’à la mise en place d’une configuration adaptée aux conditions antarctiques. Des simulations complémentaires en 3D ont par la suite soulevé l’importance du transfert radiatif infrarouge et de la paramétrisation des flux turbulents de surface pour la modélisation de la couchelimite sur le plateau pendant la nuit polaire. Enfin, les travaux de thèse ont été étendus à la modélisation des couches limites stables continentales. Les paramétrisations locales de turbulence ont en effet tendance à sous-estimer le mélange sous-maille continental, en raison de la multitude des processusde mélange en jeu. Un réflexion a donc été portée sur la façon de palier ce manque de mélange, avec comme idée directrice de transférer la perte d’énergie cinétique grande échelle perdue lors du freinage de l’écoulement par les ondes de gravité, vers de l’énergie cinétique turbulente

The extreme atmospheric boundary layer over the Antarctic Plateau and its representation in climate models

L’observation des couches limites atmosphériques au dessus du plateau antarctique a mis en évidence les plus fortes inversions de température proches de la surface de la planète. Bien paramétriser ces couches limites extrêmes dans un modèle de circulation générale est essentiel pour represéntercorrectement l’inversion climatologique de température au dessus du plateau, mais également pour reproduire des vents catabatiques réalistes en aval du plateau et de surcroit, une circulation atmosphérique correcte dans l’hémisphère sud. Les conclusions des précédentes "Gewex AtmosphericBoundary Layer Studies" (GABLS) ont conduit au constat que la paramétrisation des couches limites stables dans les modèles climatiques est une des priorités pour la communauté des modélisateurs.Ceci est dû au fait que la nature même des processus physiques en jeu est mal connue mais aussi parce que les lois de similitudes, sur lesquelles les paramétrisations du mélange turbulent sont fondées, ne sont pas applicables en condition très stable. L’objectif de ces travaux de thèse est d’évaluer et d’améliorer la représentation des couches limites sur le plateau antarctique dans le modèle français de circulation générale Laboratoire de MétéorologieDynamique-Zoom (LMDZ), composante atmosphérique du modèle de climat IPSL. Avant l’évaluation même du modèle, une étude approfondie de la couche limite de surface et de la structure de la couche limite stable a été conduite à partir de l’analyse de mesures in situ au Dôme C. Il en a résulté une caractérisation de la hauteur de rugosité aérodynamique, une estimation des flux turbulents de surface sur une année entière ainsi que la mise en évidence de sursaturations de la vapeur d’eau par rapport à la glace. L’analyse des mesures de température et de vent le long d’une tour de 45 m a aussi montré que la couche limite se comporte tel un système dynamique à deux régimes distincts. La relation entrevitesse du vent et inversion de température décrit un "S renversé", suggérant une transition de régime suivant un hystérésis. Une étude complémentaire a révélé que ce comportement dynamique à deux régimes est une caractéristique générale et robuste des couches limites stables, qui peuvent transiter,selon l’intensité des forçages, d’un régime ’turbulent’ peu stable à un régime ’radiatif’ très stable et vice et versa.Le modèle LMDZ a ensuite été évalué en configuration 1D sur un cycle diurne d’été dans le cadre de la quatrième expérience GABLS. Des tests de sensibilité aux paramètres de surface et à la paramétrisation du mélange turbulent ont été réalisés. Ils ont conduit à de nettes améliorations des performancesdu modèle ainsi qu’à la mise en place d’une configuration adaptée aux conditions antarctiques. Des simulations complémentaires en 3D ont par la suite soulevé l’importance du transfert radiatif infrarouge et de la paramétrisation des flux turbulents de surface pour la modélisation de la couchelimite sur le plateau pendant la nuit polaire. Enfin, les travaux de thèse ont été étendus à la modélisation des couches limites stables continentales. Les paramétrisations locales de turbulence ont en effet tendance à sous-estimer le mélange sous-maille continental, en raison de la multitude des processusde mélange en jeu. Un réflexion a donc été portée sur la façon de palier ce manque de mélange, avec comme idée directrice de transférer la perte d’énergie cinétique grande échelle perdue lors du freinage de l’écoulement par les ondes de gravité, vers de l’énergie cinétique turbulente.Observation of the Atmospheric Boundary Layers (ABL) above the Antarctic Plateau has revealed the strongest near-surface temperature stratifications on the Earth. A correct parametrization of the very stratified Antarctic ABLs in General Circulation Models (GCM) is critical since they exert a strongcontrol on the continental scale temperature inversion, on the coastal katabatic winds and subsequently on the Southern Hemisphere circulation. The previous Gewex Atmospheric Boundary Layer Studies (GABLS) highlighted that the parametrization of the very stratified, or very stable, ABLs isone of the most critical challenge in the atmospheric modelers community. Indeed, the nature of the mixing processes are not completely understood and the commonly used similarity laws, on which the model’s parametrization are usually based, are no longer valid. The aim of this PhD work is to evaluate and improve the modelling of the ABL over the Antarctic Plateau by the Laboratoire de Météorologie Dynamique-Zoom (LMDZ) GCM, the atmospheric component of the IPSL Earth System Model in preparation for the sixth Coupled Models Intercomparison Project. Before the model evaluation itself, an in-depth study of the dynamics of the atmospheric surface layer and of the stable ABL over the Antarctic Plateau was carried out from in situ measurements at Dome C. The analysis enabled the first estimations of the roughness length and of the surface fluxes during the polar night at this location as well as the characterization of very frequent occurences of near-surface moisture supersaturations with respect to ice. Investigation of meteorological measure-ments along a 45 m tower also revealed two distinct dynamical regimes of the stable ABL at this location. In particular, the relation between the near surface inversion amplitude and the wind speed takes a typical ’reversed S-shape’, suggesting a system obeing with an hysteresis. A further analysisshowed that this is a clear illustration of a general and robust feature of the stable ABL systems, corresponding to a ‘critical transition’ between a steady turbulent and a steady ‘radiative’ regime. LMDZ was then run on 1D simulations during a typical clear-sky summertime diurnal cycle in the framework of the fourth GABLS case. Sensitivity tests to surface parameters, vertical grid and turbulent mixing parametrizations were performed leading to significant improvements of the model and to a new configuration better adapted for Antarctic conditions. 3D simulations were then carried outwith the ’zooming capability’ of the horizontal grid and with nudging. These simulations enabled a further evaluation of the model over a full year and extending the analysis beyond Dome C. In particular, this study raised the importance of the radiative scheme and of the surface layer scheme forthe modelling of the ABL during the polar night over the Plateau. Finally, the PhD work extented toward the modelling of the stable ABL over the other continents, assessing how the frequently underestimated subgrid mixing of momentum and heat can be compensated by a transfer of large scalekinetic energy toward turbulent kinetic energy when the flow is slowed down by orographic gravity wave drag

Les thrombopénies néonatales allo-immunes (diagnostic et traitement)

PARIS-BIUP (751062107) / SudocSudocFranceF

On the fine vertical structure of the low troposphere over the coastal margins of East Antarctica

In this study, 8 years of high-resolution radiosonde data at nine Antarctic stations are analysed to provide the first large-scale characterization of the fine vertical structure of the low troposphere up to 3 km altitude over the coastal margins of East Antarctica. Radiosonde data show a large spatial variability of wind, temperature and humidity profiles, with different features between stations in katabatic regions (e.g., Dumont d'Urville and Mawson stations), stations over two ice shelves (Neumayer and Halley stations) and regions with complex orography (e.g., McMurdo). At the Dumont d'Urville, Mawson and Davis stations, the yearly median wind speed profiles exhibit a clear low-level katabatic jet. During precipitation events, the low-level flow generally remains of continental origin and its speed is even reinforced due to the increase in the continent-ocean pressure gradient. Meanwhile, the relative humidity profiles show a dry low troposphere, suggesting the occurrence of low-level sublimation of precipitation in katabatic regions but such a phenomenon does not appreciably occur over the ice shelves near Halley and Neumayer. Although ERA-Interim and ERA5 reanalyses assimilate radiosoundings at most stations considered here, substantial - and sometimes large - low-level wind and humidity biases are revealed but ERA5 shows overall better performance. A free simulation with the regional polar version of the Weather Research and Forecasting model (Polar WRF) (at a 35 km resolution) over the entire continent shows too-strong and too-shallow near-surface jets in katabatic regions especially in winter. This may be a consequence of an underestimated coastal cold air bump and associated sea-continent pressure gradient force due to the coarse 35 km resolution of the Polar WRF simulation. Beyond documenting the vertical structure of the low troposphere over coastal East Antarctica, this study gives insights into the reliability and accuracy of two major reanalysis products in this region on the Earth. The paper further underlines the difficulty of modeling the low-level flow over the margins of the ice sheet with a state-of-the-art atmospheric model

Importance of the advection scheme for the simulation of water 1 isotopes over Antarctica by atmospheric general circulation models: a case study for present-day and Last Glacial Maximum with LMDZ-iso

International audienceAtmospheric general circulation models (AGCMs) are known to have a warm and isotopically enriched 13 bias over Antarctica. We test here the hypothesis that these biases are consequences of a too diffusive advection. 14 Exploiting the LMDZ-iso model, we show that a less diffusive representation of the advection, especially on the 15 horizontal, is very important to reduce the bias in the isotopic contents of precipitation above this area. The 16 choice of an appropriate representation of the advection is thus essential when using GCMs for paleoclimate 17 applications based on polar water isotopes. Too much diffusive mixing along the poleward transport leads to 18 overestimated isotopic contents in water vapor because dehydration by mixing follows a more enriched path 19 than dehydration by Rayleigh distillation. The near-air surface temperature is also influenced, in a more minor 20 way, by the diffusive properties of the advection scheme directly via the advection of the air and indirectly via 21 the radiative effects of changes in high cloud fraction and water vapor. A too diffusive horizontal advection 22 increases the temperature and so also contributes to enrich the isotopic contents of water vapor over Antarctica 23 through a reduction of the distillation. The temporal relationship, from Last Glacial Maximum (LGM) to present-24 day conditions, between the mean annual near-air surface temperature and the water isotopic contents of 25 precipitation for a specific location can also be impacted, with significant consequences on the paleo-26 temperature reconstruction from observed changes in water isotopes. 2

Pourquoi prescrit-on des médicaments à service médical rendu insuffisant ? (enquête d'opinion auprès de 254 médecins généralistes marnais)

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Modelling invasion dynamic in virgin ecosystems : brown trout in Kerguelen Islands

National audienc