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    Long-acting muscarinic antagonists (LAMA) in asthma: What is the best strategy?

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    International audienceThe use of long-acting muscarinic antagonists (LAMA) in asthma is supported by their mechanism of action and evidence of drug synergy with inhaled corticosteroids § long-acting b-agonists. This review discusses the scientific rationale, clinical data, and recommendations for the use of LAMA in the asthma therapeutic strategy. Adding a LAMA to a dual therapy with an inhaled corticosteroid and long-acting b-agonist has been shown to reduce exacerbations, increase asthma control, and improve quality of life, with a good safety profile. In addition, using a single inhaler device containing multiple drugs enhances patients' adherence to therapy. Some predictive factors of the efficacy of this triple therapy have been suggested in the literature: patients with a history of at least one exacerbation within the past 12 months, male patients, those younger than 65 years, and non-smokers have been reported to have a greater improvement from baseline forced expiratory volume in 1 second (FEV1) compared with patients without these characteristics, while patients with high bronchial hyperresponsiveness and persistent airway limitations (PAL) seem to show better gains in the exacerbation rate. However, eosinophil levels do not seem to predict the efficacy of LAMA. The role and long-term benefits of LAMA combined with biologic therapy in severe asthma remain uncertain, with more clinical data needed

    Développement d'une puce microfluidique de PCR quantitative pour suivre la dynamique d'une communauté synthétique de microorganismes sur vigne ayant un potentiel effet de biocontrôle contre le mildiou

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    National audienceA synthetic microbial community with potential biocontrol effects against downy mildew was developed as part of Aarti Jaswa’s PhD research. To monitor the establishment of this community on grapevine leaves, a microfluidic quantitative PCR (qPCR) chip was developed. Primers targeting each microorganism individually were designed to enable absolute quantification of each strain over time. This chip is also intended for use on environmental samples, particularly those collected by spore traps from the VISA network. It could thus provide insight into the “health status” of the vineyard by indicating the presence or absence of sentinel microorganisms targeted by the chip.Une communauté synthétique de microorganismes ayant un potentiel effet de biocontrôle contre le mildiou a été développée dans le cadre de la thèse d'Aarti Jaswa. Afin de suivre l’établissement de cette communauté sur les feuilles de vigne, une puce microfluidique de PCR (Polymerase Chain Reaction) quantitative a été mise au point. Des amorces ciblant individuellement chacun des microorganismes présents sur la puce ont été développées, dans l’objectif de pouvoir obtenir une quantification absolue des souches à tout temps. Cette puce vise aussi a être utilisée sur des échantillons environnementaux, notamment ceux récoltés par les capteurs de spores du réseau VISA. Elle pourrait ainsi donner une idée de la « bonne santé » du vignoble en indiquant la présence ou non de microorganismes sentinelles ciblés par la puce

    Protocol for real-time measurement of mitochondrial bioenergetics in 3D-cultured brain tumor stem cells using the Resipher system

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    International audienceAberrant mitochondrial function can lead to severe human diseases, including neurodegenerative diseases and cancer. Here, we describe a cell-based protocol for measuring different mitochondrial respiratory parameters using the high-resolution real-time Resipher system. We optimized this protocol on brain tumor stem cells cultured in three-dimensional spheroids. We provide essential optimization steps for cell seeding density, mitochondrial respiration modulator concentrations, running the assay, and data analysis

    Linear and nonlinear optical periodic microstructures in niobium germanate glasses by thermal poling

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    International audienceOptical microstructures imprinted in niobium germanate glasses by thermal poling were investigated by correlating Raman, phase contrast imaging, Second Harmonic Generation (SHG) and Atomic Force Microscopy (AFM) measurements. Structural characterizations by Raman microscopy have shown the presence of gradient in-plane poling effects. By varying the microscale anode designs, it has been observed that the difference between the size of the in-plane gradient poling effect and the pitch dimension of the electrode patterns can explain the refractive index contrast at the micrometer scale. SHG signals were localized in microregions located at the edges of the micropatterned anode electrode and the electro-optical origin of the second-order optical responses has been confirmed. Finally, the SHG responses of second-order optical diffraction gratings were studied. The observation of well-defined SHG optical diffraction peaks demonstrates the potential of these EFISH structuration in niobium germanate glasses for the development of nonlinear optical (NLO) micro-scale periodical designs. In this perspective, this paper demonstrated the implementation of NLO properties in germanate glasses containing a wide transmission window and promising for NLO photonic applications such as infrared wavelength conversion and electro-optical devices

    Un an de droit de la responsabilité administrative. 2nde partie : Responsabilité extracontractuelle

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    International audienc

    Landscape heterogeneity and pesticide reduction favor predation, but also grape infestation by Lobesia botrana

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    International audienceBiological pest control is a major ecosystem service and is known to depend on landscape heterogeneity. The composition and configuration of landscapes can affect natural enemy communities, trophic interactions, and pest density within agroecosystems. However, local agricultural management can interfere with natural enemy activity, so the positive effects of landscape heterogeneity may be disrupted by farming practices. Here, we studied the influence of landscape context and management options on the biological control of Lobesia botrana , one of the main insect pests of grapes. We focused on two complementary measures: predation rates, which reflect part of biological control potential, and plant damage, which reflects pest density and the associated infestation. We used a set of sentinel prey (eggs, caterpillars, pupae) to quantify predation rates across different developmental stages of the pest. The study was carried out in a landscape‐scale experimental set‐up consisting of 38 vineyards in Southwestern France. Using structural equation models, we show that predation rates on sentinel prey were affected by both landscape heterogeneity and local management practices. Higher pest predation rates were observed in landscapes with smaller vineyards and in vineyards with low applications of synthetic pesticides. We observed limited relationships between predation rates and grape infestation levels. However, our results suggest that predation rates at the pest pupae stage are significantly shaping infestation levels. Additionally, pest damage in spring and summer was primarily influenced by the intensity of local pesticide use and the grass cover in the field and exacerbated by the decreasing size of vineyards, while semi‐natural habitats had no effect on pest damage. We conclude that links between L. botrana infestation and biological control potential appear tenuous in our study region. This is likely due to the high local management intensity, as evidenced by the negative association observed between pesticide applications and predation rates. Nevertheless, both predation and infestation respond to landscape or field heterogeneity and pesticide use. Reducing the use of pesticides should be combined with multi‐scale diversification measures at field and landscape levels to amplify the predation potential

    Euclid: Early Release Observations -- Programme overview and pipeline for compact- and diffuse-emission photometry

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    International audienceThe Euclid ERO showcase Euclid's capabilities in advance of its main mission, targeting 17 astronomical objects, from galaxy clusters, nearby galaxies, globular clusters, to star-forming regions. A total of 24 hours observing time was allocated in the early months of operation, engaging the scientific community through an early public data release. We describe the development of the ERO pipeline to create visually compelling images while simultaneously meeting the scientific demands within months of launch, leveraging a pragmatic, data-driven development strategy. The pipeline's key requirements are to preserve the image quality and to provide flux calibration and photometry for compact and extended sources. The pipeline's five pillars are: removal of instrumental signatures; astrometric calibration; photometric calibration; image stacking; and the production of science-ready catalogues for both the VIS and NISP instruments. We report a PSF with a full width at half maximum of 0.16" in the optical and 0.49" in the three NIR bands. Our VIS mean absolute flux calibration is accurate to about 1%, and 10% for NISP due to a limited calibration set; both instruments have considerable colour terms. The median depth is 25.3 and 23.2 AB mag with a SNR of 10 for galaxies, and 27.1 and 24.5 AB mag at an SNR of 5 for point sources for VIS and NISP, respectively. Euclid's ability to observe diffuse emission is exceptional due to its extended PSF nearly matching a pure diffraction halo, the best ever achieved by a wide-field, high-resolution imaging telescope. Euclid offers unparalleled capabilities for exploring the LSB Universe across all scales, also opening a new observational window in the NIR. Median surface-brightness levels of 29.9 and 28.3 AB mag per square arcsec are achieved for VIS and NISP, respectively, for detecting a 10 arcsec x 10 arcsec extended feature at the 1 sigma level

    Are oldest old patients with diffuse large B-cell lymphoma different than their younger counterparts: Results from the REALYSA real-life cohort

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    International audienceINTRODUCTION: Over a half of diffuse large B-cell lymphoma (DLBCL) cases are diagnosed in adults aged 65 years and older. Older adults are a heterogeneous group, and few studies reported differences in care management and survival in the oldest old. We aimed to describe characteristics, care management, and survival of older adults aged 60 and over included in the REal-world dAta in LYmphoma and Survival in Adults (REALYSA) study. MATERIALS: and methods: Patients newly diagnosed with DLBCL, aged over 60 years, included in REALYSA cohort between 2018/11 and 2021/12 and receiving therapy (RCHOP/miniRCHOP/Other) were included. Sociodemographic, living area and clinical characteristics, as well as the type of care center and pathway during the first year after diagnosis were described by age (60-69 y/70-79 y/≥80 y). Survival was described using Kaplan-Meier curves, the Cox model for adjusted survival, and net survival (Pohar-Perme estimator). RESULTS: A total of 560 DLBCL patients with a median age at diagnosis of 72 years (IQR=67-77) were included. R-CHOP was the main curative treatment in patients aged 60-79, and R-miniCHOP in the oldest old. More than half of the patients were male, married or in a relationship, living in urban and low deprived area. With increasing age, the proportion of patients with performance status 0-1 or no Charlson comorbidity at diagnosis decreased. Two thirds of patients were diagnosed at advanced stage with comparable trends between age groups. However, the oldest patients were more likely to have high-risk disease and geriatric frailty at diagnosis. One-year net survival, in contrast to OS (91 %vs 95 % and 75 % for each age group), showed no significant reduction in survival for 80 + (93 %, 100 % and 87 % for each age group). CONCLUSION: As the fastest-growing age group in developed countries, the oldest old require a special attention and further work on this population is needed

    Les cartes nous mentent-elles ?

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    Régulation des urgences bucco-dentaires au sein du service de médecine bucco-dentaire et chirurgie orale du Centre hospitalier de Mayotte, de juin 2020 à mai 2024

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    In a context of significant healthcare inequalities, this thesis explores the organization and effectiveness of dental emergency regulation at the Centre Hospitalier de Mayotte (CHM) between June 2020 and May 2024. Mayotte, a French overseas department, is marked by rapid demographic growth, widespread poverty, limited healthcare access, and a critical shortage of dental surgeons. To address the overwhelming demand, the CHM implemented a telephone regulation system supervised by a dentist. This descriptive epidemiological study is based on 28,295 calls registered through a structured questionnaire. Results show that pain is the leading reason for calls (61%), followed by abscesses (24%) and dental trauma (3%). The regulation process prioritizes infectious and traumatic cases, ensuring prompt care despite constrained resources. This study highlights the importance of structured regulation in a vulnerable, underserved context. It also explores the social, linguistic, and territorial determinants of oral health in Mayotte. It concludes with recommendations to enhance the efficiency and equity of emergency dental care delivery in remote and precarious settings.Dans un contexte de fortes inégalités d’accès aux soins, cette thèse s’intéresse à l’organisation et à l’efficacité du tri des urgences dentaires au Centre Hospitalier de Mayotte (CHM) entre juin 2020 et mai 2024. Mayotte, département français d’outre-mer, se caractérise par une démographie explosive, une grande précarité, un accès difficile aux soins et une pénurie marquée de chirurgiens-dentistes (2,8 pour 100 000 habitants en 2024). Face à un afflux constant de patients, le CHM a mis en place un système de régulation téléphonique supervisé par un chirurgien-dentiste. Cette étude épidémiologique descriptive repose sur l’analyse de 28 295 appels enregistrés via un questionnaire structuré. Les résultats révèlent que la douleur constitue le premier motif d’appel (61 %), suivie par les abcès (24 %) et les traumatismes (3 %). La hiérarchisation des urgences favorise la prise en charge rapide des infections et des traumatismes, avec une capacité de réponse satisfaisante malgré les moyens limités. Cette étude met en lumière les enjeux d’un tri structuré en contexte de précarité et de tension sanitaire. Elle interroge également les déterminants sociaux, linguistiques et territoriaux de la santé à Mayotte. Elle propose enfin des pistes d’amélioration pour une prise en charge plus équitable et efficiente des urgences bucco-dentaires

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