The GRAVITY instrument software / High-level software

GRAVITY is the four-beam, near- infrared, AO-assisted, fringe tracking, astrometric and imaging instrument for the Very Large Telescope Interferometer (VLTI). It is requiring the development of one of the most complex instrument software systems ever built for an ESO instrument. Apart from its many interfaces and interdependencies, one of the most challenging aspects is the overall performance and stability of this complex system. The three infrared detectors and the fast reflective memory network (RMN) recorder contribute a total data rate of up to 20 MiB/s accumulating to a maximum of 250 GiB of data per night. The detectors, the two instrument Local Control Units (LCUs) as well as the five LCUs running applications under TAC (Tools for Advanced Control) architecture, are interconnected with fast Ethernet, RMN fibers and dedicated fiber connections as well as signals for the time synchronization. Here we give a simplified overview of all subsystems of GRAVITY and their interfaces and discuss two examples of high-level applications during observations: the acquisition procedure and the gathering and merging of data to the final FITS file.Comment: 8 pages, 7 figures, published in Proc. SPIE 9146, Optical and Infrared Interferometry IV, 91462

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Journal of gastrointestinal surgery

We present the laboratory demonstration of a very high-dynamic range imaging instrument FIRST (Fibered Imager foR Single Telescope). FIRST combines the techniques for aperture masking and a single-mode fiber interferometer to correct wavefront errors, which leads to a very high-dynamic range up to 106 around very near the central object (~ λ/D) at visible to near-infrared wavelengths. Our laboratory experiments successfully demonstrated that the original image can be reconstructed through a pupil remapping system. A first on-sky test will be performed at the Lick Observatory 3- m Shane telescope for operational tests in the summer of 2010

LIM homeobox-2 suppresses hallmarks of adult and pediatric liver cancers by inactivating MAPK/ERK and Wnt/beta-catenin pathways

International audienceIntroduction: Hepatocellular carcinoma and hepatoblastoma are two liver cancers characterized by gene deregulations, chromosomal rearrangements, and mutations in Wnt/beta-catenin (Wnt) pathway-related genes. LHX2, a transcriptional factor member of the LIM homeobox gene family, has important functions in embryogenesis and liver development. LHX2 is oncogenic in many solid tumors and leukemia but its role in liver cancer is unknown. Methods: We analyzed the expression of LHX2 in hepatocellular carcinoma and hepatoblastoma samples using various transcriptomic datasets and biological samples. The role of LHX2 was studied using lentiviral transduction, in vitro cell-based assays (growth, migration, senescence, apoptosis), molecular approaches (phospho-kinase arrays, RNA-seq), bioinformatics and two in vivo models in chicken and Xenopus embryos. Results: We found a strong connection between LHX2 down-regulation and Wnt activation in these two liver cancers. In hepatoblastoma, LHX2 downregulation correlated with multiple poor outcome parameters including higher patient age, intermediate- and high-risk tumors and low patients’ survival. Forced expression of LHX2 reduced the proliferation, migration and survival of hepatoma cells in vitro through the inactivation of MAPK/ERK and Wnt signals. In vivo, LHX2 impeded the development of tumors in chick embryos and repressed the Wnt pathway in Xenopus embryos. RNA-sequencing data and bioinformatic analyses confirmed the deregulation of many biological functions and molecular processes associated with cell migration, cell survival and liver carcinogenesis in LHX2-expressing hepatoma cells. At a mechanistic level, LHX2 mediated the disassembling of beta-catenin/T-cell factor 4 complex and induced expression of multiple inhibitors of Wnt (e.g. TLE/Groucho) and MAPK/ERK (e.g. DUSPs) pathways. Conclusion: Collectively, our findings demonstrate a tumor suppressive function of LHX2 in adult and pediatric liver cancers

Papauté, monachisme et théories politiques. Volume II

Les soixante-six études rassemblées dans ces deux volumes veulent témoigner de la vitalité et du profond renouvellement de l'histoire médiévale politique et religieuse. Elles sont offertes par ses collègues français et étrangers à Marcel Pacaut, qui en fut un des plus actifs représentants durant plus de trente ans d'enseignement à l'Université de Lyon. Le volume II : Les Eglises locales, envisagées ici sous deux angles : - L'analyse des structures ecclésiales dans, depuis le diocèse jusqu'à la paroisse, où se modèle au quotidien la vie religieuse et spirituelle des fidèles. - L'étude d’un cas précis – celui des églises des anciens pays bourguignons (royaume d'Arles, duché de Bourgogne) – ancrage nécessaire d’une recherche soucieuse d’approcher le plus concrètement possible les réalités humaines, pour pouvoir mieux les replacer ensuite dans les grands courants de l'histoire générale

Discordance du temps

La centralité de l'urgence et les bouleversements des rythmes sociaux produisent de nouveaux régimes temporels, qui remettent en cause les liens et les pratiques communicationnels, les pratiques de transmission et de médiation. Ces mutations, dont les multiples conséquences restent à évaluer, ont déjà retenu l'attention d'anthropologues, d'historiens, d'économistes, de politologues ou de philosophes. Le présent ouvrage propose une approche communicationnelle des enjeux et des problèmes suscités par ces mutations temporelles. Le laboratoire MICA (Médiation, Information, Communication, Arts), équipe d'accueil de la formation doctorale en Sciences de l'information de la Communication et en Arts de l'Université Michel de Montaigne - Bordeaux 3, a déjà tenu plusieurs colloques et réalisé des travaux sur les temporalités médiatiques et l'urgence communicationnelle. Il s'agit ici, à partir des bénéfices de ces premières investigations et des éclairages apportés par les recherches les plus récentes, de prolonger cette réflexion