Conception d'un dispositif expérimental et étude de l'écoulement oscillant en résonateur acoustique fort niveau pour la caractérisation de phénomènes non-linéaires: transition à la turbulence et écoulements redressés

Two of nonlinear acoustic phenomena of high acoustic level are studied in this thesis: the transition to turbulence and the streaming flow in an acoustic wave guide. The recent development of Laser measurement techniques such as Laser Doppler Velocimetry (LDV) allow to reconsider the study of these phenomena. Part of the present work consists in the adaptation of LDV to acoustic measurements in the near wall region. This makes it possible to begin thereafter the study of the transition to turbulence in a compressible oscillating fluid and the study of the inner and outer streaming especially for high acoustic levels. For this purpose, an experimental set-up was designed, carried out, instrumented and characterized on the basis of the study of the coupled electroacoustic system: source / acoustic resonator. To isolate the studied phenomena, the other non linear phenomena which can appear in the wave guide (nonlinear propagation and minor losses at geometric discontinuity) are quantified. LDV measurements of acoustic velocity and turbulence in the acoustic boundary layer make it possible to specify the evolution of the flow regimes which appear in the transition to turbulence and to determine an experimental limit between a laminar flow and a turbulent flow for our measurements. Velocity measurements of acoustic streaming are performed to study the evolution of the inner and outer acoustic streaming especially for high acoustic levels. A preliminary study was also carried out in order to study the effect of an obstacle on the Rayleigh cells so as to help understand of phenomena in thermoacoustic machines.Deux phénomènes de l'acoustique non-linéaire à fort niveau sont étudiés lors de cette thèse: la transition à la turbulence et les écoulements redressés en guide d'onde acoustique. Le développement récent de la Vélocimétrie Laser par effet Doppler (VLD) ouvre de nouvelles voies pour l'étude de ces phénomènes. Une partie du travail de cette thèse a ainsi consisté en l'adaptation de la VLD à des mesures acoustiques en proche paroi. Ce travail préliminaire a permis de proposer par la suite l'étude de la transition à la turbulence en fluide oscillant compressible et celle des tourbillons internes et externes des écoulements redressés. Pour ce faire, un dispositif expérimental a été conçu, réalisé, instrumenté et caractérisé, impliquant en particulier une étude de l'ensemble couplé source acoustique / résonateur. Pour isoler les phénomènes à l'étude, les autres phénomènes non-linéaires qui peuvent apparaître dans le guide d'onde sont évalués. Des mesures par VLD de vitesse acoustique et de turbulence dans la couche limite acoustique permettent de préciser l'évolution des régimes d'écoulements qui interviennent dans la transition à la turbulence et de déterminer une limite expérimentale entre le régime laminaire et le régime turbulent. Des mesures de la vitesse des écoulements redressés sont effectuées pour observer l'évolution des tourbillons internes et externes des écoulements redressés, en particulier pour des écoulements redressés rapides. Une étude préliminaire est aussi effectuée en vue d'étudier l'influence d'un obstacle sur le schéma de Rayleigh pour aider à la compréhension des phénomènes présents dans les machines thermoacoustiques

Conception d'un dispositif expérimental et étude de l'écoulement oscillant en résonateur acoustique fort niveau pour la caractérisation de phénomènes non-linéaires (transition à la turbulence et écoulements redressés)

Deux phénomènes de l'acoustique non-linéaire à fort niveau sont étudiés lors de cette thèse: la transition à la turbulence et les écoulements redressés en guide d'onde acoustique. Le développement récent de la Vélocimétrie Laser par effet Doppler (VLD) ouvre de nouvelles voies pour l étude de ces phénomènes. Une partie du travail de cette thèse a ainsi consisté en l adaptation de la VLD à des mesures acoustiques en proche paroi. Ce travail préliminaire a permis de proposer par la suite l étude de la transition à la turbulence en fluide oscillant compressible et celle des tourbillons internes et externes des écoulements redressés. Pour ce faire, un dispositif expérimental a été conçu, réalisé, instrumenté et caractérisé, impliquant en particulier une étude de l'ensemble couplé source acoustique / résonateur. Pour isoler les phénomènes à l'étude, les autres phénomènes non-linéaires qui peuvent apparaître dans le guide d'onde sont évalués. Des mesures par VLD de vitesse acoustique et de turbulence dans la couche limite acoustique permettent de préciser l'évolution des régimes d'écoulements qui interviennent dans la transition à la turbulence et de déterminer une limite expérimentale entre le régime laminaire et le régime turbulent. Des mesures de la vitesse des écoulements redressés sont effectuées pour observer l'évolution des tourbillons internes et externes des écoulements redressés, en particulier pour des écoulements redressés rapides. Une étude préliminaire est aussi effectuée en vue d'étudier l'influence d'un obstacle sur le schéma de Rayleigh pour aider à la compréhension des phénomènes présents dans les machines thermoacoustiques.Two of nonlinear acoustic phenomena of high acoustic level are studied in this thesis: the transition to turbulence and the streaming flow in an acoustic wave guide. The recent development of Laser measurement techniques such as Laser Doppler Velocimetry (LDV) allow to reconsider the study of these phenomena. Part of the present work consists in the adaptation of LDV to acoustic measurements in the near wall region. This makes it possible to begin thereafter the study of the transition to turbulence in a compressible oscillating fluid and the study of the inner and outer streaming especially for high acoustic levels. For this purpose, an experimental set-up was designed, carried out, instrumented and characterized on the basis of the study of the coupled electroacoustic system: source / acoustic resonator. To isolate the studied phenomena, the other non-linear phenomena which can appear in the wave guide (nonlinear propagation and minor losses at geometric discontinuity) are quantified. LDV measurements of acoustic velocity and turbulence in the acoustic boundary layer make it possible to specify the evolution of the flow regimes which appear in the transition to turbulence and to determine an experimental limit between a laminar flow and a turbulent flow for our measurements. Velocity measurements of acoustic streaming are performed to study the evolution of the inner and outer acoustic streaming especially for high acoustic levels. A preliminary study was also carried out in order to study the effect of an obstacle on the Rayleigh cells so as to help understand of phenomena in thermoacoustic machines.POITIERS-BU Sciences (861942102) / SudocSudocFranceF

Modal decomposition in ducts based on pressure measurements with a microphonic antenna

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Setting up an experimental apparatus for the study of multimodal acoustic propagation with turbulent mean flow

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Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

International audienceDown syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS

Outcome of Patients With Resected Early-Stage Non-small Cell Lung Cancer and EGFR Mutations: Results From the IFCT Biomarkers France Study

International audienceINTRODUCTION: Molecular profile of resected stage I-II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I-II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population. PATIENTS AND METHODS: Surgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations. RESULTS: In the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively. CONCLUSION: In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study

BACKGROUND: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. METHODS: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged 6575 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (<75 years vs 6575 years). Treatments were assigned based on a permuted blocked randomisation scheme with a block size of four. The isatuximab-pomalidomide-dexamethasone group received isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, number NCT02990338. FINDINGS: Between Jan 10, 2017, and Feb 2, 2018, we randomly assigned 307 patients to treatment: 154 to isatuximab-pomalidomide-dexamethasone, and 153 to pomalidomide-dexamethasone. At a median follow-up of 11\ub76 months (IQR 10\ub71-13\ub79), median progression-free survival was 11\ub75 months (95% CI 8\ub79-13\ub79) in the isatuximab-pomalidomide-dexamethasone group versus 6\ub75 months (4\ub75-8\ub73) in the pomalidomide-dexamethasone group; hazard ratio 0\ub7596, 95% CI 0\ub744-0\ub781; p=0\ub7001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab-pomalidomide-dexamethasone vs pomalidomide-dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab-pomalidomide-dexamethasone group and 14 (9%) in the pomalidomide-dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (<1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection). INTERPRETATION: The addition of isatuximab to pomalidomide-dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor. FUNDING: Sanofi. VIDEO ABSTRACT

Carbon monoxide and prognosis in smokers hospitalised with acute cardiac events: a multicentre, prospective cohort studyResearch in context

Summary: Background: Smoking cigarettes produces carbon monoxide (CO), which can reduce the oxygen-carrying capacity of the blood. We aimed to determine whether elevated expiratory CO levels would be associated with a worse prognosis in smokers presenting with acute cardiac events. Methods: From 7 to 22 April 2021, expiratory CO levels were measured in a prospective registry including all consecutive patients admitted for acute cardiac event in 39 centres throughout France. The primary outcome was 1-year all-cause death. Initial in-hospital major adverse cardiac events (MAE; death, resuscitated cardiac arrest and cardiogenic shock) were also analysed. The study was registered at ClinicalTrials.gov (NCT05063097). Findings: Among 1379 patients (63 ± 15 years, 70% men), 368 (27%) were active smokers. Expiratory CO levels were significantly raised in active smokers compared to non-smokers. A CO level >11 parts per million (ppm) found in 94 (25.5%) smokers was associated with a significant increase in death (14.9% for CO > 11 ppm vs. 2.9% for CO ≤ 11 ppm; p  11 ppm was associated with a significant increase in MAE in smokers during initial hospitalisation after adjustment for comorbidities (odds ratio [OR] 15.75, 95% CI [5.56–44.60]) or parameters of in-hospital severity (OR 10.67, 95% CI [4.06–28.04]). In the overall population, CO > 11 ppm but not smoking was associated with an increased rate of all-cause death (HR 4.03, 95% CI [2.33–6.98] and 1.66 [0.96–2.85] respectively). Interpretation: Elevated CO level is independently associated with a 6-fold increase in 1-year death and 10-fold in-hospital MAE in smokers hospitalized for acute cardiac events. Funding: Grant from Fondation Coeur & Recherche

L’âge du Fer en Basse-Normandie. Gestes funéraires en Gaule au Second-Âge du Fer. Volumes I et II

Cet ouvrage est la publication des actes du 33e colloque international de l’AFEAF, qui s’est tenu à Caen, du 20 au 24 mai 2009. De même que le colloque, il comprend deux parties. La première, qui contient dix-sept contributions, traite de l’actualité des recherches sur l’Âge du fer en Basse-Normandie, une région qui a connu un renouvellement important de la documentation permettant d’appréhender les dynamiques d’occupation et les formes d’organisation territoriale durant la Protohistoire. Plusieurs bilans synthétiques concernant l’habitat rural, les sites fortifiés et la culture matérielle, sont, entre autres, proposés ici. La seconde partie de l’ouvrage traite du thème de la mort et des pratiques funéraires durant la période Ve-Ier siècles avant J.-C. ; elle contient vingt-deux contributions. Ce sujet a été abordé en privilégiant quelques axes de réflexion, de façon à faciliter les comparaisons entre régions. À travers des bilans synthétiques, le thème spécialisé du colloque est traité à l’échelle de la Gaule, avec les éclairages de plusieurs régions de l’Europe celtique.This is the publication of the proceedings of the 33rd AFEAF symposium held in Caen from the 20th to the 24th of May 2009. Like the symposium, this book is divided in two parts. The first part, with its 17 contributions, deals with the current knowledge about the Iron Age in Lower Normandy. An important renewal of the documentation concerning this region allows a better understanding of the occupational processes and territorial organization existing throughout Protohistory. This first part also includes several summary reports on rural settlements, fortified sites as well as finds. The second part of the book, with 22 contributions, deals with the subject of death and funerary practices during the 5th to 1st centuries BC. The subject was discussed focussing on a chosen number of thoughts as to make it easier to compare between different regions. Various summary reports allow an overview of this specialized topic throughout Gaul with perspectives from other regions of Celtic Europe