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Low-Tidal-Volume Ventilation and Mortality in Patients With Acute Brain Injury: A Secondary Analysis of an International Observational Study
No full textInternational audienceBackground: Low-tidal-volume ventilation (LTVV) improves outcomes in critically ill patients, but its impact in patients with acute brain injuries (ABIs) is less certain.Research question: What is the association between LTVV and mortality in mechanically ventilated patients with ABI?Study design and methods: We did a secondary analysis of a prospective observational study (NCT03400904; https://clinicaltrials.gov/study/NCT03400904). We compared LTVV (≤ 8 mL/kg predicted body weight [PBW]) with tidal volumes > 8 mL/kg PBW over the first 7 days of mechanical ventilation. Alternate analyses used lower thresholds for LTVV. Marginal structural Cox models were used to evaluate the association between LTVV and ICU mortality up to 60 days. Stabilized inverse probability treatment and censoring weights were generated using multivariable logistic regression adjusted for baseline and time-dependent confounders.Results: A total of 1,510 patients from 73 ICUs across 18 countries were included. The mean age was 52 years, 513 patients (34.0%) were female, and the most common ABI etiology was traumatic brain injury (n = 726; 48.1%). ARDS developed in 137 patients (9.2%). In patients receiving LTVV, adjusted incidence of ICU mortality was 40.2% (95% CI, 19.2%-61.1%), vs 59.7% (95% CI, 44.0%-75.4%) in patients receiving tidal volumes > 8 mL/kg PBW (marginal hazard ratio, 0.54; 95% CI, 0.33-0.88). There was no heterogeneity of treatment effect in subgroup analyses, and sensitivity analyses for unmeasured confounding yielded similar results. However, associations were less clear at lower thresholds of LTVV.Interpretation: In this predominantly non-ARDS cohort of patients with ABI, LTVV over the first 7 days of mechanical ventilation was associated with lower ICU mortality up to 60 days, vs tidal volumes > 8 mL/kg PBW. Future research should investigate effects in patients with ABI and ARDS, use of lower LTVV thresholds, and impact on additional end points including functional outcomes and adverse events
Diagnosis and management of superficial arteriovenous malformations: French healthcare network’s recommendations
No full textInternational audienceSuperficial arteriovenous malformations are rare fast-flow lesions. They consist of arteriovenous shunts, without cellular hyperplasia or proliferation, which develop in the surrounding tissues (cutaneous, subcutaneous, muscular, bone). Although benign, they are among the most severe of superficial malformations. Their evolution can be life-threatening in exceptional cases. With the aim of optimizing diagnosis and management worldwide, this protocol offers a state of the art for the diagnosis and management of these diseases. To this end, the French healthcare network specialized in these diseases have drawn on literature data and experience. Developed from the French National Diagnosis and Care Protocol, it presents the patient journeys for initial and differential diagnoses, and personalized therapeutic strategies. This requires a multidisciplinary team, with specialized professionals in handling genetic, treatment and psychosocial issues
Novel VA opsin transcript variant in tissues linked to photoperiodic time-measurement in Svalbard rock ptarmigan
No full textInternational audiencePhotoperiodic time-measurement (PTM) is a process describing how environmental light information is perceived, assessed, and ultimately translated into physiological and behavioral responses. Unlike mammals, which detect photoperiod exclusively through the eyes, birds possess multiple photoreceptive sites including the eyes, pineal gland, and deep brain photoreceptors (DBPs) located within the hypothalamus. The cellular and molecular identity of the DBPs mediating PTM remains a matter of debate, however. Vertebrate ancient opsin (VA opn) is considered a strong DBP candidate, based on its anatomical localization and spectral sensitivity. Here, we used three different RNA sequencing methods to evaluate tissue-specific patterns of VA opn expression across photoreceptive structures in the Svalbard rock ptarmigan (SRP), a highly photoperiodic galliform species adapted to the extreme light conditions of the High Arctic. In the pineal gland, over 60% of VA opn transcripts encoded a full-length VA opn, containing all seven transmembrane domains considered necessary for photoreceptor function. In vitro analysis demonstrated that this variant has peak spectral sensitivity at approximately 500 nm, consistent with published work in other galliform species. By contrast, in the hypothalamus fewer than 2% of VA opn transcripts encoded a full-length VA opn, with the majority variant predicted to lack three out of seven transmembrane domains. This novel VA opn variant, termed SRPVA, was predominantly expressed in cells of the oligodendrocytic lineage. These data support a model in which VA opn contributes to the photosensitivity of the pineal gland, but not to DBP function in the SRP
Placebo in paediatric clinical trials for alopecia areata: friend or foe?
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LHR and Gαs trafficking drive sustained cAMP signalling from endosomes to control steroidogenesis
No full text1. Summary A growing number of G protein-coupled receptors (GPCRs) signal through G proteins from intracellular compartments following endocytosis. While for few receptors the physiological relevance of such mechanism has been established, the relationships between the spatio-temporal organization of cellular signalling and the physiological responses are still to be elucidated for most receptors. Signalling by the luteinizing hormone receptor (LHR) is essential to regulate sex steroids production in gonads, but how G protein-dependent signals from endosomes are functionally important for steroidogenesis remains unexplored. Here, we demonstrate that transient LHR activation promotes a prolonged Gαs/cAMP signalling from endosomes, which requires ligand-induced independent receptor and Gαs trafficking. We show that endosomal trafficking is specifically required for ligand-induced cAMP accumulation in the nucleus and gene expression, as well as for steroids production in Leydig cells. Thus, this study contributes to further understand the molecular mechanisms by which LHR, through signalling compartmentalization, controls gonadal steroidogenesis
Super-résolution stochastique et problèmes inverses : de l'échantillonnage conditionnel gaussien aux modèles de diffusion
No full textThis thesis investigates the stochastic resolution of inverse problems in imaging, through Gaussian conditional sampling and diffusion models. It primarily focuses on super-resolution, which aims to enhance the resolution of an image from a low-resolution version, and deblurring, which seeks to restore the sharpness of a blurred image.In contrast to classical deterministic approaches, we adopt a probabilistic perspective, with the goal of modeling and sampling the set of plausible images consistent with a degraded observation.The objective is to study this paradigm within a mathematically rigorous and well-founded framework. To this end, we examine Gaussian image distributions, including Gaussian microtextures associated with the Asymptotic Discrete Spot Noise (ADSN) model.We formulate the problem in a Bayesian framework, emphasizing the challenges related to conditional sampling in the Gaussian setting. We then discuss recent advances in generative modeling, particularly diffusion probabilistic models (DDPMs), which involve reversing a progressive noising process using a learned model. More specifically, we first study, via a kriging-based reasoning, the exact sampling of inverse problems for Gaussian microtextures, with a particular focus on super-resolution. This leads to the construction of an efficient and exact sampler within this restricted setting.Next, we investigate diffusion models applied to Gaussian distributions in a generative context, in order to assess their ability to provide a meaningful prior distribution over images. By leveraging the reformulation of diffusion models as stochastic differential equations (SDEs), we derive the governing equations in the linear and Gaussian case, and analyze their properties.This allows us to establish explicit results on sampling errors, notably in terms of Wasserstein distances, and to gain a better understanding of the nature of the approximations induced by the models used.Finally, we study algorithms for solving inverse problems based on diffusion models in the context of Gaussian microtexture deblurring. This enables us to highlight undesired behaviors of a sampler intended to approximate the theoretical posterior distribution.Cette thèse étudie la résolution stochastique des problèmes inverses en imagerie, à travers l'échantillonnage conditionnel gaussien et les modèles de diffusion. Elle s'intéresse principalement à la super-résolution, qui consiste à améliorer la résolution d'une image à partir d'une version basse résolution, ainsi qu'au déflouage, qui vise à restaurer la netteté d'une image floue. Contrairement aux approches déterministes classiques, nous adoptons une perspective probabiliste dont le but est de modéliser et d'échantillonner l'ensemble des images plausibles compatibles avec une observation dégradée de l'image.L'objectif est d'étudier ce paradigme dans un cadre mathématique rigoureux et bien fondé. Pour cela, nous étudions les distributions gaussiennes d'images, qui incluent les microtextures gaussiennes associées au modèle Asymptotic Discrete Spot Noise (ADSN).Nous formulons le problème dans un cadre bayésien, en mettant en avant les enjeux liés à l'échantillonnage conditionnel dans le contexte gaussien. Nous discutons ensuite des modèles génératifs récents, et en particulier des modèles de diffusion probabilistes (DDPM), qui consistent à inverser un processus de bruitage progressif à l'aide d'un modèle appris.Plus précisément, dans un premier temps, nous étudions, par un raisonnement de krigeage, l'échantillonnage exact de problèmes inverses pour les microtextures gaussiennes, avec un accent particulier sur la super-résolution. Cela nous a permis de construire un échantillonneur efficace et exact dans ce cadre restreint.Ensuite, nous étudions les modèles de diffusion appliqués aux distributions gaussiennes dans un cadre génératif, afin d'évaluer leur capacité à fournir une distribution a priori sur les images. En exploitant la reformulation des modèles de diffusion comme équations différentielles stochastiques (SDE), nous dérivons les équations en jeu dans le cas linéaire et gaussien, et en étudions les propriétés.Cela nous permet d'établir des résultats explicites sur les erreurs d'échantillonnage, notamment en termes de distances de Wasserstein, et de mieux comprendre la nature des approximations induites par les modèles utilisés. Enfin, nous étudions les algorithmes de résolution des problèmes inverses liés aux modèles de diffusion, dans le cadre du déflouage de microtextures gaussiennes. Cela nous permet de mettre en évidence des comportements non souhaités d'un échantillonneur censé approximer la probabilité a posteriori théorique
Behaviour of ewes and lambs in response to human emotional odours
No full textInternational audienceThis study investigated whether sheep (Ovis aries) discriminate the body odour of unfamiliar humans subjected to a contrastive emotion-inducing procedure. Axillary secretions were collected from 38 humans after they watched fearful or joyful films. The behavioural responses of adult ewes (n = 35) and 6-day-old lambs (n = 22) to these odours were assessed using a habituation-dishabituation paradigm validated in this species. Both ewes and lambs exhibited habituation (reduced tactile-olfactory investigation), but no significant dishabituation, limiting strong conclusions about odour discrimination. However, ewes displayed ear postures suggestive of differential emotional reactivity to assumed valence, but these effects were subtle and potentially influenced by test conditions. The lambs exposed to fear odour (FO), relative to those exposed to joy odour (JO), showed increased escape attempts and oral grasping of the odour pad, a conflicting pattern of responses that complicates interpreting FO as aversive. In sum, these results suggest that lambs may react to FO as a distinct stimulus, but they may not clearly associate it with negative valence. Ewes showed behavioural differences in response to odours, yet the absence of clear dishabituation makes it difficult to confirm discrimination ability. Further research including physiological measures is needed to clarify ovine perception of human emotional odours
"Délai d’exécution d’une ordonnance sur requête en matière probatoire : une discussion à clore"
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Regards croisés sur la culture matérielle rurale : retour sur les communications du colloque AGER XVI
No full textInternational audienceLa seizième édition du colloque AGER, organisée à Nantes du 13 au 16 novembre 2024, a interrogé les marqueurs de statuts sociaux dans les campagnes romaines des Gaules et de leurs périphéries. Cinq communications ont particulièrement abordé la question du mobilier et de son potentiel informatif pour l’analyse des hiérarchies sociales en milieu rural.Nous proposons un bilan critique de ces interventions, enrichies des autres mobilisant du mobilier archéologique dans leur réflexion comme celle présentée par les auteurs, afin de dégager des pistes de réflexion méthodologiques. Ce panorama permettra de mieux cerner les outils dont disposent les archéologues pour identifier les signes d’aisance ou de modestie dans les espaces ruraux.Les communications discutées ont abordé divers marqueurs matériels des statuts sociaux en milieu rural. Les objets en ivoire témoignent d’un luxe ostentatoire, mais leur rareté en contexte rural impose de nuancer leur valeur d’indicateur social. Dans l’ouest de la Gaule, les artefacts personnels ou d’agrément révèlent des indices modestes et variés de distinction sociale. En Rhône-Alpes, une approche quantitative croise la céramique, le verre, les soins du corps ou le jeu pour établir des référentiels différenciant les niveaux d’aisance. Dans le nord de la Gaule, certains équipements agricoles ou bâtiments peuvent être interprétés comme des objets économiques et symboliques, porteurs d’une mise en scène sociale. Enfin, en Île-de-France, l’étude du mobilier non céramique montre que la définition des statuts sociaux doit tenir compte des contextes de découverte et des biais de conservation. Ce retour d’expérience mettra en évidence les limites et les apports des approches, en posant la question de la pluralité des critères (quantitatifs, qualitatifs, contextuels) pour interpréter le statut social à partir du mobilier. Il ouvrira aussi la discussion sur les perspectives d’intégration de ces données
Comparative analysis of PIPAC nozzle designs: ex vivo evaluation of aerosol distribution, penetration, and tissue concentration
No full textInternational audienceBackgroundA comparative ex vivo study was conducted to evaluate the impact of different nebulizer designs on spatial distribution, tissue concentration, and penetration depth of drugs delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC).Materials and MethodsThree nebulizer designs were evaluated in a PIPAC box: group 1 [full spray cone-multidirectional nebulizer (FSC-MDN)], group 2 [full spray cone-single directional nebulizer], and group 3 [hollow spray cone-single directional nebulizer]. Spatial aerosol deposition was measured using methylene blue for three-dimensional gravimetry in gram (g). PIPACs with doxorubicin and cisplatin were performed to assess penetration depth (mu m) and drug concentrations (mu g/g) in porcine peritoneal tissue samples from the bottom, sides, and top of the box. Doxorubicin penetration was evaluated using fluorescence microscopy, and cisplatin concentrations were quantified using inductively coupled plasma mass spectrometry.ResultsGroup 3 had significantly higher methylene blue deposition at the bottom (35.59 +/- 1.46 g) compared with group 1 (24.2 +/- 0.23 g, p = 0.0022) and group 2 (31.47 +/- 0.52 g, p = 0.0001). Conversely, group 1 showed significantly greater side and top deposition (10.11 +/- 0.26 g) than groups 2 (5.01 +/- 0.68 g, p = 0.0022) and 3 (3.99 +/- 0.42 g, p = 0.0022). Group 1 also demonstrated higher cisplatin concentrations (6.254 +/- 2.57 mu g/g, p = 0.05) and deeper doxorubicin penetration (179.9 +/- 78.77 mu m, p = 0.05) than the other groups.ConclusionsCompared with the other single directional nebulizers, group 1 (FSC-MDN) achieved greater side and top deposition, along with enhanced doxorubicin penetration and platinum concentration in the ex vivo PIPAC model