La compréhension des mécanismes qui pilotent la transmission des contraintes aux interfaces déformables est au centre de nombreuses problématiques touchant des applications actuelles utilisant un ...film mince de polymère souple comme couche interfaciale. Arriver à caractériser de tels films fins est encore un défi aujourd’hui car l’analyse des mesures expérimentales destinées à extraire les contributions dues aux films est complexe et délicate et les techniques usuelles de caractérisation sont peu adaptées aux systèmes. Ce travail étudie la réponse mécanique de deux types de systèmes modèles au moyen de deux techniques de caractérisation différentes. Le premier système que nous avons élaboré et caractérisé mécaniquement par le test JKR, est constitué de films d’élastomère réticulé d’épaisseurs micrométriques (de 5 à 100µm) et déposés sur des wafers de silicium. Les mesures expérimentales ont été analysées par comparaison à un modèle semi-analytique récent proposé par E. Barthel dans le but d’extraire le module élastique de chaque film et de répondre à la question de savoir si l’épaisseur du film influe sur la valeur de ce module. Nous avons montré que ce modèle permet de rendre compte quantitativement du raidissement lié à la présence d’un solide supportant le film mais que la précision sur les mesures de modules de Young reste limitée (de l’ordre de 35 %).Le deuxième système modèle est constitué de brosses de polymères greffées (PDMS) par une extrémité à la surface de wafers de silicium et gonflées dans un bon solvant (47V20). Nous avons analysé la réponse mécanique dans plusieurs régimes de distance et de fréquence en utilisant un appareil à forces de surface (SFA) dans lequel on contrôle l’approche d’une sphère millimétrique d’un plan sur lequel sont greffées les polymères. En statique, nous avons vérifié que la réponse en compression était celle d’une brosse de type Alexander-de Gennes. En mode dynamique, quand la sphère est loin de la couche gonflée, nous avons vérifié que la réponse dissipative était celle d’un écoulement de Reynolds qui décrit normalement l’écoulement d’un fluide simple newtonien entre une sphère et un plan solide. Ceci nous a permis de montrer que l’écoulement du solvant pénètre partiellement à l’intérieur de la couche greffée sur une profondeur de l’ordre du tiers de l’épaisseur gonflée de la couche. Dans le régime ou les brosses sont comprimées, il n’y a pas d’accord entre les mesures réalisées et le modèle classique de Fredrickson et Pincus. Ceci s’explique par les expériences que nous avons réalisées sur un substrat nu (sans polymère) montrant pour la première fois la déformation des substrats solides qui sont indentés par l’écoulement de liquide et qu’il faut prendre en compte cette déformation dans les analyses de nanorhéologie. Finalement, une annexe est consacrée à la fabrication de surfaces hydrophobes silanisées optimisées en vue d’étudier le glissement d’un liquide simple et d’électrolytes à la paroi.
Understanding how stresses are transmitted to deformable interfaces is a key-point in numerous issues having everyday life applications which use a thin polymer film as an interfacial layer. Still, characterizing the mechanical properties of such elastic films remains a challenge because the usual employed techniques are destructive of the surface and because of the complexity of the associated analysis. In this work, we study the mechanical response of two types of home-made model systems using two different characterization techniques. The first system – studied with a JKR test- is composed of reticulated elastomeric films of micrometric thickness (5 to 100 µm) and stuck to a silicon wafer. We analyse the experimental data with E.Barthel’s recently published semi-analytical model in order to determine the elastic modulus of each indented film and see if the thickness of the film had any influence on its value. We show that this model is in a quantitatively good agreement with our data but that we only have a 35% accuracy on the elastic modulus values thanks to the set-up. The second system we studied consists in polymer brushes end-grafted onto the surface of silicon wafers and of nanometric thickness. To characterize the mechanical response of those brushes and the effect of both their molecular organization and ingredients on their ability to transmit stresses at the interface, we use a surface force apparatus in the dynamic mode as a soft fluid indenter. We use a millimetric sphere to create a liquid flow of the solvent in which the brushes are immerged and swollen. This flow induces hydrodynamic forces whose range we can control by varying the excitation frequency and the distance of approach. We obtain the following results : first with the static response we checked that the response of the polymer layers are well-described by the Alexander-de Gennes approximation. In the dynamical mode, when the sphere is far from the solid surface, we showed that the dissipative response was well-described by the Reynolds force. Thanks to those results, we succeeded in localizing the limit of penetration of the liquid flow inside the brushes at one third of the thickness of the swollen brush; second, when the brushes are compressed, we showed that the existing models (Fredrickson & Pincus) are insufficient to explain the dynamic responses of the brushes. This disagreement is explained by experiments we performed on the bare solid substrate, which show for the first time, the deformation of the substrate due to the liquid. Thus, the mechanical response of the underlying substrate has to be taken into account in the analysis of the nanorheological results on the brushes even though the substrate is much stiffer than the polymer layers. Finally, we present how we fabricated hydrophobic (silanized) surfaces in order to study the sliding of simple liquids at the wall with the same surface force apparatus.
Regarding male fertility, biomedical issues have opposite goals to treat infertility or develop contraceptive drugs. Recently, the identification of the molecular mechanisms involved in germ cell ...differentiation suggest that spermiogenesis has to be put at the crossroad to reach these goals.
Concerning fertility issues, citizens in our modern world are schizophrenic. On one side, couples have the possibility to control conception; and on the other side, more and more couples suffer from the misfortune of being infertile. These two societal problems lead to intensive research and conflicting government policies. However, these opposing goals rely on a better understanding of germ cell differentiation.
La compréhension des mécanismes qui pilotent la transmission des contraintes aux interfaces déformables est au centre de nombreuses problématiques touchant des applications actuelles utilisant un ...film mince de polymère souple comme couche interfaciale. Arriver à caractériser de tels films fins est encore un défi aujourd'hui car l'analyse des mesures expérimentales destinées à extraire les contributions dues aux films est complexe et délicate et les techniques usuelles de caractérisation sont peu adaptées aux systèmes. Ce travail étudie la réponse mécanique de deux types de systèmes modèles au moyen de deux techniques de caractérisation différentes. Le premier système que nous avons élaboré et caractérisé mécaniquement par le test JKR, est constitué de films d'élastomère réticulé d'épaisseurs micrométriques (de 5 à 100µm) et déposés sur des wafers de silicium. Les mesures expérimentales ont été analysées par comparaison à un modèle semi-analytique récent proposé par E. Barthel dans le but d'extraire le module élastique de chaque film et de répondre à la question de savoir si l'épaisseur du film influe sur la valeur de ce module. Nous avons montré que ce modèle permet de rendre compte quantitativement du raidissement lié à la présence d'un solide supportant le film mais que la précision sur les mesures de modules de Young reste limitée (de l'ordre de 35 %).Le deuxième système modèle est constitué de brosses de polymères greffées (PDMS) par une extrémité à la surface de wafers de silicium et gonflées dans un bon solvant (47V20). Nous avons analysé la réponse mécanique dans plusieurs régimes de distance et de fréquence en utilisant un appareil à forces de surface (SFA) dans lequel on contrôle l'approche d'une sphère millimétrique d'un plan sur lequel sont greffées les polymères. En statique, nous avons vérifié que la réponse en compression était celle d'une brosse de type Alexander-de Gennes. En mode dynamique, quand la sphère est loin de la couche gonflée, nous avons vérifié que la réponse dissipative était celle d'un écoulement de Reynolds qui décrit normalement l'écoulement d'un fluide simple newtonien entre une sphère et un plan solide. Ceci nous a permis de montrer que l'écoulement du solvant pénètre partiellement à l'intérieur de la couche greffée sur une profondeur de l'ordre du tiers de l'épaisseur gonflée de la couche. Dans le régime ou les brosses sont comprimées, il n'y a pas d'accord entre les mesures réalisées et le modèle classique de Fredrickson et Pincus. Ceci s'explique par les expériences que nous avons réalisées sur un substrat nu (sans polymère) montrant pour la première fois la déformation des substrats solides qui sont indentés par l'écoulement de liquide et qu'il faut prendre en compte cette déformation dans les analyses de nanorhéologie. Finalement, une annexe est consacrée à la fabrication de surfaces hydrophobes silanisées optimisées en vue d'étudier le glissement d'un liquide simple et d'électrolytes à la paroi.
It is essential to fight against malnutrition and dehydration in elderly people in care facilities. They result in the deterioration of the general status, a risk of a fall, a risk of wounds, an ...increased risk of infection and mortality in geriatrics. In addition, swallowing disorders due to ageing increase the risk of food going down the wrong way. Those involved in the multidisciplinary care management pool their skills in support of the elderly person.
BACKGROUND:Streptococcus pneumoniae remains an important cause of bacterial meningitis in children younger than 2 years. Here, we analyzed data from an active surveillance network established 12 ...years ago by the Pediatric Infectious Disease Group and the Pediatric Clinical and Therapeutical Association to analyze the impact of pneumococcal conjugate vaccine (PCV7 implemented in 2002 and PCV13 in 2010) on pneumococcal meningitis (PM).
METHODS:Two hundred twenty-seven pediatric wards working with 168 microbiology departments throughout France were asked to report all cases of PM.
RESULTS:From 2001 to 2012, among 4808 bacterial meningitis cases, 1406 cases of PM (29.2%) were reported. After PCV13 implementation, from 2009 to 2012, the number of cases significantly decreased by 27.4% (P = 0.041, Cuzick trend test). For children younger than 2 years, the decrease was 28.2% (P = 0.039, Cuzick trend test). In the same period, the decrease was 66.7% in cases due to 6 additional PCV13 types, and the number of cases due to nonvaccine types remained stable. In 2012, the non-PCV13 serotype represented 67.6% of cases and were mainly represented by 12F (15%), 24F (15%), 22F (7%) and 15B/C (7%). For 88.6% of cases, initial antibiotic treatment was vancomycin with a third-generation cephalosporin. Overall mortality was 10.6%, most deaths (86.4%) occurred before day 15.
CONCLUSIONS:Two years after the PCV13 implementation, we found an impact on PM cases particularly for children younger than 2 years.
The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in France since June 2010. The aim of this study was to evaluate the trends in the incidence of invasive pneumococcal disease ...(IPD) resulting in hospitalization of children younger than 18 years of age, to identify the vaccination status of these patients and to analyze the serotypic evolution of the pneumococci involved in the various types of IPD.
This multicenter retrospective study reviewed all admissions of children younger than 18 years of age for IPD from 2014 through 2018 in all hospitals with a pediatric or neonatal unit in northern France. Data completeness was obtained by matching 3 independent databases. The incidence of IPD resulting in hospitalization was calculated per age group. The clinical course and the vaccine and nonvaccine types were described overall and by the IPD type.
One hundred thirty cases of IPD were identified: 51 with bacteremia, 45 meningitis, 28 pneumonia or pleuropneumonia and 6 arthritis. The IPD incidence ranged from 2.4 to 3.0/100,000 in children under 18 years of age (95% confidence intervals, 1.4-3.3 and 1.9-4.1, respectively), and from 9.5 to 15.9/100,000 in children under 2 years of age, with no significant differences over time. Nonvaccine types were predominant (81%), mainly 24F, 23B and 10A. Vaccine serotype 3 was involved in 10 cases of IPD, 2 of which were in correctly vaccinated children. Two cases of IPD could have been prevented by vaccination. Neurologic sequelae affected 26% of these children (62% of those with meningitis). Six children died from IPD (5%).
The incidence of IPD resulting in hospitalization remained stable in northern France during the study period, with no significant increase in nonvaccine types. Further surveillance is needed to adjust the vaccination strategy if necessary.
Azithromycin was rapidly adopted as a repurposed drug to treat coronavirus disease 2019 (COVID-19) early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19.
In a ...series of randomised, open-label, phase 2 proof-of-concept, multicentre clinical trials (Direct Antivirals Working against the novel coronavirus (DAWn)), several treatments were compared with standard of care. In 15 Belgian hospitals, patients hospitalised with moderate to severe COVID-19 were allocated 2:1 to receive standard of care plus azithromycin or standard of care alone. The primary outcome was time to live discharge or sustained clinical improvement, defined as a two-point improvement on the World Health Organization (WHO) ordinal scale sustained for at least 3 days.
Patients were included between April 22 and December 17, 2020. When 15-day follow-up data were available for 160 patients (56% of preset cohort), an interim analysis was performed at request of the independent Data Safety and Monitoring Board. Subsequently, DAWn-AZITHRO was stopped for futility. In total, 121 patients were allocated to the treatment arm and 64 patients to the standard-of-care arm. We found no effect of azithromycin on the primary outcome with a hazard ratio of 1.044 (95% CI 0.772-1.413; p=0.7798). None of the predefined subgroups showed significant interaction as covariates in the Fine-Gray regression analysis. No benefit of azithromycin was found on any of the short- and longer-term secondary outcomes.
Time to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19.
The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the ...hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19.
DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician's discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days.
The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context.
EU Clinical trials register EudraCT Nb 2020-001614-38 . Registered on 22 April 2020.
IMPORTANCE: In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises ...concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. OBJECTIVE: To assess the long-term outcome of PCV13 implementation on CAP in children. DESIGN, SETTING, AND PARTICIPANTS: This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography–confirmed CAP were included. EXPOSURES: Community-acquired pneumonia. MAIN OUTCOMES AND MEASURES: The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed using a segmented regression model, adjusted for influenza-like illness syndromes. RESULTS: We enrolled 12 587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (−0.8% per month 95% CI, −1.0% to −0.5% per month), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month 95% CI, 0.4%-1.4% per month), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (−48% 95% CI, −84% to −12%), CAP requiring hospitalization (−30% 95% CI, −56% to −5%), and CAP with high inflammatory biomarkers (−30% 95% CI, −54% to −6%), without any rebound thereafter. CONCLUSIONS AND RELEVANCE: The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.
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