SiGe HBTs Optimization for Wireless Power Amplifier Applications

This paper deals with SiGe HBTs optimization for power amplifier applications dedicated to wireless communications. In this work, we investigate the fT-BVCEO tradeoff by various collector optimization schemes such as epilayer thickness and dopant concentration, and SIC and CAP characteristics. Furthermore, a new trapezoidal base Germanium (Ge) profile is proposed. Thanks to this profile, precise control of Ge content at the metallurgical emitter-base junction is obtained. Gain stability is obtained for a wide range of temperatures through tuning the emitter-base junction Ge percent. Finally, a comprehensive investigation of Ge introduction into the collector (backside Ge profile) is conducted in order to improve the fT values at high injection levels

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

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

SUBSTANCES ANTIVIRALES ACTIVES CONTRE LES VIRUS DU GENRE ALPHAVIRUS (FAMILLE DES TOGAVIRIDAE) (SYNERGIE D'ACTION DE L'ASSOCIATION INTERFERON-RIBAVIRINE IN VITRO)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

Pre-Sabine room acoustic design guidelines based on human voice directivity

International audienc

Architectural acoustic design: Observation of use cases including audio-only and multimodal auralizations

International audienceAuralization technology has reached a satisfactory level of ecological validity, enabling its use in architectural acoustic design. Only recently have the actual uses of auralization in the consulting community been explored, resulting in the identification of a variety of uses, including (1) to present to clients, (2) to test design ideas, (3) as a verification tool, (4) as a verification tool, (5) as a marketing tool, and (6) to improve internal company discussions. Taking advantage of methodologies from ergonomics research, the present study investigates effective uses through the observation of a collaboration project between an acoustic research team and an acoustic consultant, as a case study. Two spaces have been auralized in the context of the conception of a new skyscraper during the design phase of the project. The two spaces faced different problematics: an Atrium for which three different acoustic treatment options were suggested and experienced through multi-modal auralizations and audio-only auralizations of an Auditorium where an intrusive noise was to be acoustically treated. The ergonomic observation and analysis of this project revealed key impediments to the integration of auralization in common acoustic design practices

SEGAE, SErious Game for AgroEcology learning : un « jeu-sérieux » pour enseigner l’agroécologie à l’échelle d’une exploitation de polyculture-élevage laitier

International audienceL’agriculture européenne se doit de produire plus durablement. L’agroécologie est perçue comme un moyen d’atteindre cet objectif de production en conciliant les dimensions sociale, économique et environnementale de l’agriculture durable (Rockström et al. 2017). L’agroécologie est ici définie comme l’étude des interactions entre les plantes, les animaux, l’environnement et les pratiques des agriculteurs (Dalgaard et al., 2003).Afin d’accompagner la transition agroécologique des systèmes de production, il est nécessaire de former les futurs professionnels à l’interdisciplinarité et à l’approche systémique. L’utilisation d’un jeu sérieux (ou serious game) semble un moyen pertinent pour atteindre cet objectif car il permet à l’apprenant : i) d’acquérir de façon active, ludique et, autonome, des notions complexes dans une situation proche de la réalité (Vassileff, 2003) en ayant des retours immédiats sur ses actions ; ii) d’appréhender les interactions entre les différents éléments du système de production tout comme les conséquences de changements de pratiques sur le fonctionnement de ce dernier.Le jeu-sérieux SEGAE a été conçu dans cette optique, dans le cadre du projet Erasmus+ SEGAE regroupant 6 universités européennes. Ce travail décrit le jeu SEGAE et discute de sa pertinence en tant que support pédagogique pour appréhender les concepts d’agroécologie à l’échelle d’une exploitation de polyculture-élevage laitier

Energetic dysfunction in sepsis: a narrative review

International audienceBackground Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions. Main text Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described. Conclusions Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies

Second-tier trio exome sequencing after negative solo clinical exome sequencing: an efficient strategy to increase diagnostic yield and decipher molecular bases in undiagnosed developmental disorders

International audienceDevelopmental disorders (DD), characterized by malformations/dysmorphism and/or intellectual disability, affecting around 3% of worldwide population, are mostly linked to genetic anomalies. Despite clinical exome sequencing (cES) centered on genes involved in human genetic disorders, the majority of patients affected by DD remain undiagnosed after solo-cES. Trio-based strategy is expected to facilitate variant selection thanks to rapid parental segregation. We performed a second step trio-ES (not only focusing on genes involved in human disorders) analysis in 70 patients with negative results after solo-cES. All candidate variants were shared with a MatchMaking exchange system to identify additional patients carrying variants in the same genes and with similar phenotype. In 18/70 patients (26%), we confirmed causal implication of nine OMIM-morbid genes and identified nine new strong candidate genes (eight de novo and one compound heterozygous variants). These nine new candidate genes were validated through the identification of patients with similar phenotype and genotype thanks to data sharing. Moreover, 11 genes harbored variants of unknown significance in 10/70 patients (14%). In DD, a second step trio-based ES analysis appears an efficient strategy in diagnostic and translational research to identify highly candidate genes and improve diagnostic yield

Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3

Self-renewal and differentiation of pluripotent murine embryonic stem cells (ESCs) is regulated by extrinsic signaling pathways. It is less clear whether cellular metabolism instructs developmental progression. In an unbiased genome-wide CRISPR/Cas9 screen, we identified components of a conserved amino-acid-sensing pathway as critical drivers of ESC differentiation. Functional analysis revealed that lysosome activity, the Ragulator protein complex, and the tumor-suppressor protein Folliculin enable the Rag GTPases C and D to bind and seclude the bHLH transcription factor Tfe3 in the cytoplasm. In contrast, ectopic nuclear Tfe3 represses specific developmental and metabolic transcriptional programs that are associated with peri-implantation development. We show differentiation-specific and non-canonical regulation of Rag GTPase in ESCs and, importantly, identify point mutations in a Tfe3 domain required for cytoplasmic inactivation as potentially causal for a human developmental disorder. Our work reveals an instructive and biomedically relevant role of metabolic signaling in licensing embryonic cell fate transitions