Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The automatic recognition of the calcareous nannofossils of the Cenozoic

SYRACO est un SYstème de Reconnaissance Automatisée des COccolithes, développé à son origine par Luc Beaufort et Denis Dollfus à partir de 1995 et plus récemment avec Yves Gally. L'utilité d'un tel système est de permettre aux spécialistes un gain de temps majeur dans l'acquisition et le traitement des données. Dans ce travail, le système a été amélioré techniquement et sa reconnaissance a été étendue aux nannofossiles calcaires du Cénozoïque. Ce système fait le tri entre les nannofossiles et les non-nannofossiles avec une efficacité respectivement estimée à 75% et 90 %. Il s'appuie sur une nouvelle base d'images de référence d'espèces datant de l'Eocène Supérieur aux espèces vivantes, ce qui représente des centaines d'espèces avec une forte variabilité morphologique. Il permet de réaliser une classification en 39 morphogroupes par la combinaison de réseaux de neurones artificiels avec des modèles statistiques. Les résultats sont présentés sous forme de comptages automatisés, de données morphométriques (taille, masse...) et de mosaïques d'images. Il peut ainsi être utilisé pour des analyses biostratigraphiques et paléocéanographiques.SYRACO is an automated recognition system of coccoliths, originally developed since 1995 by Luc Beaufort and Denis Dollfus, and more recently with the help of Yves Gally. The main purpose of this system is for specialists to save time in the acquisition and treatment of data. By this recent work, the system has been technically improved and its ability of recognition has been extended to calcareous nannofossils of the Cenozoic Era. It sorts nannofossils and non-nannofossils with a reliability respectively estimated to 75% and 90%. It is based on a new reference images database of species from the Upper Eocene up to living species. This represents hundreds of species with a high morphological variability. It leads to the establishment of a classification arranged in 39 morphogroups, combining artificial neural networks to statistical models. The results are presented as automated counting, morphometrical data (size, mass...) and mosaics of images. Those results can be valuable in biostratigraphical and paleoceanographical analyses

LA RECONNAISSANCE AUTOMATISÉE DES NANNOFOSSILES CALCAIRES DU CÉNOZOÏQUE

SYRACO is an Automated Recognition SYstem of COccoliths, originally developed since 1995 by Luc Beaufort and Denis Dollfus, and more recently with the help of Yves Gally. The main purpose of this system is for specialists to save time in the acquisition and treatment of data. By this recent work, the system has been technically improved and its ability of recognition has been extended to calcareous nannofossils of the Cenozoic Era (Upper Eocene). It sorts nannofossils and non-nannofossils with a reliability respectively estimated to 75% and 90%. It is based on a new database of reference images using species from the Upper Eocene up to living ones. This represents hundreds of species with a high morphological variability. It leads to the establishment of a classification arranged in 39 morphogroups, combining artificial neural networks to statistical models. The results are presented as automated counting, morphometrical data (size, mass, etc.) and mosaics of images. Those results can be valuable in biostratigraphical and paleoceanographical analyses. The results on the core MD052930 (Gulf of Papoua) highlight major ecologic changes on the last 800,000 years: the acme of Emiliania huxleyi, the rise of the small Gephyrocapsa, the acme of Gephyrocapsa caribbeanica and the last occurrence of Pseudoemiliania lacunosa and Discoaster. These events lead to the determination of biozonations used in biostratigraphy. It is also possible to study primary paleoproductivity with the help of the automated counting of Florisphaera profunda. While on the other hand, a study about the morphologic distribution of the Noelaerhabdaceae (around 350.000 individuals) highlights that the ecological events used in biostratigraphy are observable through the evolution of the size and mass distributions. Moreover, these results show that the eccentricity and the precession modulate the variance of the morphologic distribution (size, mass and mean thickness). These influences are reverberated by periods of bimodal distributions of the sizes during high eccentricity. By this study, SYRACO unveils a new potential for the stratigraphy using the coccoliths: the cyclo-morpho-chronostratigraphy that would enable to reach a resolution up to 20,000 years, or even 5,000 years.SYRACO est un SYstème de Reconnaissance Automatisée des COccolithes, développé à son origine par Luc Beaufort et Denis Dollfus à partir de 1995 et plus récemment avec Yves Gally. L'utilité d'un tel système est de permettre aux spécialistes un gain de temps majeur dans l'acquisition et le traitement des données. Dans ce travail, le système a été amélioré techniquement et sa reconnaissance a été étendue aux nannofossiles calcaires du Cénozoïque (Eocène Sup.). Ce système fait le tri entre les nannofossiles et les non-nannofossiles avec une efficacité respectivement estimée à 75% et 90 %. Il s'appuie sur une nouvelle base d’images de référence d’espèces datant de l’Eocène Supérieur aux espèces vivantes, ce qui représente des centaines d’espèces avec une forte variabilité morphologique. Il permet de réaliser une classification en 39 morphogroupes par la combinaison de réseaux de neurones artificiels avec des modèles statistiques. Les résultats sont présentés sous forme de comptages automatisés, de données morphométriques (taille, masse, etc.) et de mosaïques d’images. Il peut ainsi être utilisé pour des analyses biostratigraphiques et paléocéanographiques. Les résultats obtenus sur la carotte MD052930 (Golfe de Papouasie) mettent en évidence les changements écologiques majeurs des derniers 800 000 ans : l’acmé d’Emiliania huxleyi, l’augmentation des petits Gephyrocapsa, l’acmé de Gephyrocapsa caribbeanica et la dernière occurrence de Pseudoemiliania lacunosa et de Discoaster. Ces évènements permettent de déterminer la biozonation utilisée en biostratigraphie. Il est possible aussi d’étudier la paléoproductivité primaire grâce au comptage automatique de Florisphaera profunda. D’autre part, une étude sur la distribution morphologique des Noelaerhabdaceae (environ 350 000 individus) met en évidence que les évènements écologiques utilisés en biostratigraphie sont observables par le biais de la distribution de la taille ou de la masse. De plus, ces résultats montrent que l’excentricité et la précession modulent la variance de la distribution morphologique (taille, masse et épaisseur moyenne). Ces influences se répercutent par des périodes de distributions bimodales de la taille lors d’une forte excentricité.Par cette étude, SYRACO dévoile un nouveau potentiel pour la stratigraphie grâce aux coccolithes : la cyclo-morpho-chronostratigraphie qui permettrait d’atteindre des résolutions de 20 000 ans, voire de 5 000 ans

Differences in Late Quaternary primary productivity between the western tropical Pacific and the South China Sea: Evidence from coccoliths

International audienceChanges in Late Quaternary oceanic primary productivity in the western tropical Pacific were reconstructed using coccolith counts from the improved SYRACO system in piston core MD01-2386 retrieved from the Halmahera Sea near northwest New Guinea. The calculated primary productivity exhibits cycles on obliquity and precession timescales over the last 192 ka. There are marked differences between primary productivity records from the western tropical Pacific and the South China Sea (SCS), with the former being dominated by precession, and the latter showing all three Milankovitch cycles (eccentricity, obliquity and precession). Empirical Orthogonal Function (EOF) analyses reveal two significant EOF modes in the western tropical Pacific and SCS records. EOF-1 accounts for 38% of the total variance and exhibits obvious precessional cycles corresponding to Northern Hemisphere summer insolation, while EOF-2 accounts for 22% of the total variance and exhibits strong 41-kyr periodicity, suggesting different biological responses to hydroclimate changes in the two regions. A more complex hydroclimate regime influenced by the East Asian monsoon and the large contrast in regional topography and circulation during glacial cycles are considered to be the primary drivers of the stronger temporal variability in productivity in the SCS compared to the relatively stable western tropical Pacific. (C) 2015 Elsevier Ltd. All rights reserved

Chantiers lyonnais du Moyen Âge (Saint-Jean, Saint-Nizier, Saint-Paul)

Les monuments du Moyen Âge parvenus jusqu'à nous contiennent les traces de leur histoire, profondément imprimées dans leur architecture. Dans leur extrême diversité, ces traces constituent une mémoire vive que sait décrypter la lecture archéologique des élévations. Les trois église lyonnaises, Saint-Jean, Saint-Nizier, Saint-Paul, représentent un demi millénaire d'architecture, quatre siècles d'aménagements et de réparations, trois décennies de restaurations, quinze ans de recherche en archéologie du bâti. En d'autres termes, ce sont de véritables conservatoires des arts de bâtir et des techniques de conservation ; mais aussi de formidables laboratoires de recherche et d'expérimentation, où ont travaillé de concert archéologues et restaurateurs. Les connaissances acquises sur ces trois édifices majeurs offrent une vision profondément renouvelée des chantiers de construction à Lyon au Moyen Âge ainsi que des méthodes de conservation, archéologiquement attestées depuis le xvie siècle. Elles englobent également le domaine de l'esthétique monumentale, tant dans le vocabulaire architectural que dans les matériaux et les techniques de mise en œuvre. Elles concernent aussi l'environnement des églises, c'est-à-dire leur rapport étroit avec la ville. Elles éclairent, enfin, les pratiques et les activités que ces édifices ont abritées et abritent encore : liturgie, rassemblements, travaux d'entretien et d'embellissement. Nicolas Reveyron, professeur d'histoire de l'art et d'archéologie à l'Université Lumière-Lyon 2, a été de tous les chantiers ; il se devait d'être le maître d'oeuvre de ce magnifique volume qui restitue une aventure collective, mais aussi une tranche de vie de chercheur et de pédagogue.À la mémoire de Brigitte Oberlin, Brigitte Oberlin est décédée alors que s'achevait la préparation de ce volume. Toute l'équipe des DARA est affligée par la perte d'une collègue et, pour certains d'entre nous, d'une amie très chère. Brigitte fut et restera l'artisan de la première heure ; c'est à elle, en effet, que la collection doit d'exister. On se souvient qu'en 1988, les DARA prenaient la suite des RAPRRA (Rapports archéologiques préliminaires de la région Rhône-Alpes) dont Brigitte avait assuré la réalisation quatre années durant avec une disponibilité sans faille. Elle a, par la suite, apporté un concours assidu à la gestion et à la diffusion de la collection, secrètement fière de son succès. Toujours sensible à l'investissement humain que requiert le travail de rédaction et d'édition en archéologie, elle a contribué à l'ouverture de la collection aux chercheurs d'une vaste région et aux indispensables liens de confiance entre les auteurs et l'équipe éditoriale. Ce sont les messages qu'elle nous a laissés. À nous tous de leur rester fidèles

Middle Jurassic coccolith fluxes: A novel approach by automated quantification

International audienceCoccolithophores, major pelagic carbonate producers, underwent important changes during the latest Aalenian–Early Bajocian (ca. − 170 Ma, Middle Jurassic). Specifically, a new genus called Watznaueria diversified and started dominating the coccolith assemblages. While this change in the coccolith assemblages is already known, the impact on coccolith absolute abundances and fluxes is still misunderstood. Here we tested for the first time on Mesozoic deposits an automated counting method using the SYRACO system, and then compared these results with a classic counting method. Two neural networks were created based on the shape, birefringence and size of coccoliths, the first of which contained only one class and the second of which was composed of six classes. Based on the morphological criteria used for the neural networks, coccoliths were not identified at the species level. We quantified coccolith absolute abundances and estimated fluxes for the latest Aalenian–Early Bajocian in two well-dated and correlated sections, Cabo Mondego in Portugal and Chaudon-Norante in France. There is a strong linear correlation between classic and automatic counting (r > 0.8) supporting the latter as a reliable method for coccolith absolute abundance and flux quantification. In spite of under- or over-estimation by automatic counting with respect to classic counting, the absolute abundance stratigraphic trends are remarkably similar. Under- or over-estimation may be reduced by further technical improvements such as automatic focus. At Cabo Mondego, coccolith fluxes increased from 0.2 × 109 coccoliths/m2/yr in the latest Aalenian to 700 × 109 coccoliths/m2/yr in the middle of the Laeviuscula ammonite Zone (Early Bajocian), remaining high for the rest of the Early Bajocian. At Chaudon-Norante, a similar trend was observed. This coccolith flux increase is therefore considered to be a supra-regional event matching an important δ13CBulk carbonate positive excursion. The carbon isotopic positive excursion, along with the onset of radiolarian sedimentation and coccolith fluxes is related to a gradual increase in the fertility of the oceans during the Early Bajocian and is likely associated with warmer and more humid climates and associated enhanced continental weathering

Cool episode and platform demise in the Early Aptian: new insights on the links between climate and carbonate production.

15 pagesInternational audienceThe Early Aptian encountered several crises in neritic and pelagic carbonate production, majorperturbations in the carbon cycle, and an oceanic anoxic event (OAE1a). Yet the causal links betweenthese perturbations and climate changes remain poorly understood, partly because temperature recordsspanning the Early Aptian interval are still scant. We present new δ18O data from well-preserved bivalves froma carbonate platform of the Galve subbasin (Spain) that document a major cooling event postdating mostof OAE1a. Our data show that cooling postdates the global platform demise and cannot have triggeredthis event that occurred during the warmest interval. The warmest temperatures coincide with the timeequivalent of OAE1a and with platform biotic assemblages dominated by microbialites at Aliaga as well as onother Tethyan platforms. Coral-dominated assemblages then replace microbialites during the subsequentcooling. Nannoconids are absent during most of the time equivalent of the OAE1a, probably related to thewell-known crisis affecting this group. Yet they present a transient recovery in the upper part of this intervalwith an increase in both size and abundance during the cool interval portion that postdates OAE1a. Anevolution toward cooler and drier climatic conditions may have induced the regional change from microbialto coral assemblages as well as nannoconids size and abundance increase by limiting continent-derivedinput of nutrients

The Valanginian isotope event: a complex suite of palaeoenvironmental perturbations.

17 pagesInternational audienceThe Valanginian records a severe crisis of carbonate systems, both on platforms and in the pelagic realm. This crisis is roughly concomitant with the Weissert Event, characterized by a positive δ13C excursion of about 2‰in marine carbonates. However, it is unclear if the response of these two carbonate systems to the global perturbations is contemporaneous, or if they react differently. For this purpose, accumulation rates of pelagic carbonates produced by nannofossils and of platform-derived carbonates have been quantified in a hemipelagic environment (the Vocontian Basin, SE France) that has the potential to record the reaction of both shallow-water and pelagic carbonate production to a major perturbation of the carbon cycle, testified by the isotope excursion. Also, changes through time of clay input have been measured in order to evaluate variations in continental weathering rates, and thus in continent-derived nutrient input and climatic conditions in terms of humidity/aridity. Accumulation rates of pelagic carbonates, of platform-derived carbonates and of clays were calculated on the basis of nannofossil absolute abundance and species-specific masses, of weight percent carbonate content of rocks, and a high-resolution timescale given by cyclostratigraphy. The onset of the positive δ13C excursion and the demise of the platforms testify for a synchronous, but inverse response of the shallow-water and pelagic carbonate systems to an increase in nutrient influx to marine waters. As carbonate production by nannofossils decreased during the Late Valanginian in time of still low platform production, the low temperature of marine waters coeval to a still high nutrient input recorded in the latest Late Valanginian possibly could explain that both platform and pelagic carbonate production contemporaneously decreased

Fiber Bragg Grating Dynamic Extensometry on Metallic Samples submitted to High Pulse Power Magnetic Fields

International audienceIsentropic compression of metallic samples under High Pulse Powers (HPPs) are performed at CEA-Gramat. Large strains and high strain rates are obtained under intense magnetic field-driven Laplace forces. On account on electromagnetic immunity, a dedicated Fiber Bragg Grating (FBG) mainframe was designed by CEA LIST. Ring aluminum samples with crossed FBGs bonded onto the external surface were tested on the CYCLOPE HPP facility. Dynamic strain measurements were performed along with Photonic-Doppler Velocimetry (PDV). FBG strain data compare well to strain data derived from PDV displacements, leading the way to direct dynamic extensometry in the purpose of improving Magneto-Hydro-Dynamics (MHD) codes

Evidence for a complex Valanginian nannoconid decline in the Vocontian basin (South East France).

17 pagesInternational audienceThe Early Cretaceous is punctuated by widespread biocalcification crises. These are characterized by decrease in the carbonate platform growth and, in the pelagic realm, by a decline in Nannoconus relative abundance in the calcareous nannofossil assemblages. The Valanginian Nannoconus decline started before the positive δ13C excursion characterizing the Weissert Event. The nannoconid decline is investigated in two sections of the Vocontian Basin, La Charce and Vergol, which are biostratigraphically well-constrained and contain wellpreserved calcareous nannofossils. Absolute and relative abundances of Nannoconus show a polyphased decline, with a first decrease in the interval from the Campylotoxus to the Verrucosum Ammonite Subzones before the positive δ13C shift, and a second decrease from the end of the Peregrinus to the base of the Radiatus Ammonite Zones concomitant with the long-term decrease in δ13C. These two declines are separated by an important increase in the Nannoconus abundance from the Verrucosum to the Peregrinus Ammonite Subzones concomitant with a slight short-term decrease of δ13C. Biometric analysis shows size changes of N. steinmannii and N. kamptneri along the nannoconid decline. The patterns of abundances and size changes seem to be related to paleoenvironmental changes, mainly characterized by a temperature decrease and variable nutrient supply. The described Valanginian nannoconid recovery seems to occur during the most intense phase of the cooling event and is recorded in the Vocontian basin as well as in the Atlantic and Tethys Oceans. These spatial correlations suggest a supra-regional character for the Valanginian nannoconid recovery event best recorded in the Vocontian Basin and at low latitudes