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Comprehensive analysis of CNOT3-related neurodevelopmental disorders: phenotypic and genotypic characterization
No full textInternational audienceThe CCR4-NOT complex, crucial in gene expression regulation, includes CNOT3, a subunit linked to neurodevelopmental disorders when mutated. This study investigates 51 patients from 42 families with heterozygous CNOT3 variants, aiming to expand the understanding of CNOT3-related neurodevelopmental disorders and explore genotype-phenotype correlations. Patients originated from various countries, reflecting the disorder's global significance. All patients exhibited developmental delays, particularly in the language area. Intellectual disability was found in 87% of patients and was typically mild to moderate. Behavioral issues, including autism spectrum disorders and attention deficits, were common, affecting over half of the patients. Dysmorphic features were highlighted and may help establishing the diagnosis. Epilepsy was uncommon (10%). Twenty-eight novel variants were identified, including missense, nonsense, frameshift, intronic variations and a deletion of 12 exons. Missense variants clustered at the N- and C-terminal regions of the protein, indicating critical functional roles. No clear genotype-phenotype correlation was observed, suggesting that all identified variants resulted in a loss-of-function effect. Finally, this work delineates the clinical and molecular spectrum of CNOT3-related disorders thanks to an in-depth characterization of a large cohort. Further research will be necessary to understand the functional consequences of the variants and enhance patient long-term outcomes
Enjeux de collaboration entre consultants-techniciens et décideurs publics : le cas de la Convention Citoyenne pour le Climat
No full textInternational audienceThis contribution proposes to study the role of the consultant-technician in the deployment of participatory systems. Thus, our research is based on the analysis of the internal organization of Civic Tech start-ups and on the issues of collaboration between consultant-technicians and public decision-makers. We will focus on the start-up Open Source Politics on the grounds of the Citizens’ Climate Convention. From a methodological point of view, this research is structured around a series of semi-structured interviews. This is to understand how the profession of consultanttechnician works in a context of state platformization.La présente contribution propose d'étudier le rôle du consultant-technicien dans le déploiement des dispositifs participatifs. Ainsi, notre recherche s'appuie sur l'analyse de l'organisation interne des start-ups de la Civic Tech et sur les enjeux de collaboration entre les consultants-techniciens et les décideurs publics. Nous placerons la focale du côté de la start-up Open Source Politics sur le terrain de la Convention Citoyenne pour le Climat. D'un point de vue méthodologique, cette recherche se structure autour d'une série d'entretiens semi-directifs. Ceci pour comprendre le fonctionnement du métier de consultant-technicien dans un contexte de plateformisation de l'État
Unraveling Ceftriaxone Dosing: Free Drug Prediction, Threshold Optimization, and Model Validation
No full textInternational audienceCeftriaxone is pivotal in treating severe infections; however, predicting unbound plasma ceftriaxone (CEFu) from total ceftriaxone (CEFtot) remains challenging. This study aimed to (1) predict CEFu from CEFtot, (2) determine optimal target for CEFtot trough concentration in plasma, (3) perform an external validation of published models, and (4) to ascertain whether the CEF dosing regimen was sufficient to achieve the therapeutic objectives. CEFu predictions based on CEFtot were evaluated using previously published models. Optimal CEFtot targets for an MIC of 1mg/L were calculated to achieve CEFu concentrations above MIC and 4xMIC 100% of the time. External validation was conducted assessing serum albumin, CEFtot and CEFu and comparing predicted CEFu across models. Retrospective data, comprising 408 CEFtot from 222 patients, were analyzed to assess the probability of target attainment (PTA) based on model predicted CEFu. CEFu predictions based on CEFtot were evaluated using previously published models. Optimal CEFtot targets for an MIC of 1mg/L were calculated to achieve CEFu concentrations above MIC and 4xMIC 100% of the time. External validation was conducted assessing serum albumin, CEFtot and CEFu and comparing predicted CEFu across models. Retrospective data, comprising 408 CEFtot from 222 patients, were analyzed to assess the probability of target attainment (PTA) based on model predicted CEFu. Optimal CEFtot trough concentration targets ranged from 2.0 mg/L to 16.9 mg/L (1xMIC) and from 7.9 mg/L to 56.2 mg/L (4xMIC) across models. Some models accurately predicted CEFu obtained from prospective external validation. In the retrospective cohort, PTA ranged from 94.4% to 98.7% for 1xMIC and from 66.9% to 97.3% for 4xMIC. Modeling or direct quantification of CEFu may improve patient outcomes, but achieving this requires standardized analytical approaches and further research to assess the ability of published models to accurately predict CEFu
Musculoskeletal disorders in type 1 diabetes: Clinical phenotyping and associations with quality of life and glucose control - The French SFDT1 cohort study
No full textInternational audienceBackgroundMusculoskeletal disorders (MSDs) are common, but overlooked, complications of type 1 diabetes mellitus (T1DM). This study aims to describe MSD phenotypes (clinical, lifestyle, socio-economic) in adults with T1DM.MethodsWe analyzed adult participants in the SFDT1 cohort study. We assessed the following MSDs: stress fractures, non-traumatic upper-limb disorders, and entrapment syndromes. We performed a cross-sectional analysis of the association between MSDs and various factors. After applying multiple imputations for missing data, we computed logistic regression models with progressive adjustments on confounding factors.ResultsOf 1832 participants (53 % men, median age 38 (IQR 22) years), 34 % reported at least one personal history of MSD: 8 % for stress fractures, 24 % for upper-limb disorders and 15 % for entrapment syndromes. A higher prevalence of MSDs was found in women, with aging and with diabetes duration. In a fully adjusted model, we observed a positive association between current smoking (OR [95 %CI] = 1.50 [1.14;1.97]), non-excessive alcohol consumption (1.45 [1.14;1.85]), neuropathy (1.70 [1.35;2.15]), retinopathy (1.30 [1.02;1.65]), use of automated insulin delivery systems (1.53 [1.06;2.21]) and MSDs. MSDs were associated with reduced global quality of life (0.97 [0.95;0.98]). MSDs were not associated with HbA1c, social vulnerability or physical activity.ConclusionWe have shown that MSDs are found in 1 in 3 people with T1DM. They are associated with several lifestyle factors, diabetes complications and the use of automated insulin delivery systems. MSDs should be considered in the T1DM assessment to optimize quality of life
High Mortality Due to Pneumococcal Meningitis in Children With Sickle Cell Disease: A French Multicenter Observational Study From 2001 to 2021
No full textInternational audienceBackground: Sickle cell disease (SCD) predisposes children to bacterial infections, particularly invasive pneumococcal disease. Pneumococcal immunization associated with antibiotic prophylaxis reduced the incidence of invasive pneumococcal disease in these patients. However, the risk remains higher than in the general population. Our main objective was to describe the features of pneumococcal meningitis and estimate the case-fatality rate in children with SCD. The secondary objective was to assess serotype distribution and resistance patterns and the proportion of cases related to vaccine failure. Methods: This nationwide multicenter observational study was conducted in France between 2001 and 2021. All cases of pneumococcal meningitis in children with SCD < 18 years old from the French National Registry of Pediatric Pneumococcal Meningitis were included. Results: Of 2145 pneumococcal meningitis, 25 cases (1.2%, 95% CI: 0.8–1.7) occurred in children with SCD [mean age = 4.6 years (±4)], with a high case-fatality rate (28%, n = 7, 95% CI: 10.4–45.6). Nonvaccine serotypes were predominant (n = 15, 65%, 95% CI: 45.8–84.7) over vaccine serotypes (n = 8, 35%, 95% CI: 15.3–54.3). One case of vaccine failure (4%, n = 1/23) and 2 breakthrough cases (n = 2/23, 9%) were observed. Penicillin-non-susceptible Streptococcus pneumoniae strains were identified in 39% (n = 7). Conclusions: The occurrence of pneumococcal meningitis in children with SCD during the pneumococcal conjugate vaccines era was associated with a high case-fatality rate and a predominance of nonvaccine serotypes. The implementation of new serotype-expanded PCV may have a potentially positive impact on this vulnerable population
Investigation of hydrogen-plasticity interactions in Fe-bcc using finite element method
No full textInternational audiencePrediction of Hydrogen embrittlement needs to develop reliable numerical simulations accounting for interactions between hydrogen transport and mechanical behavior at different scales. Focus is made here on understanding hydrogen-plasticity interactions in bcc iron at the polycrystal scale using the finite element method.A suitable crystal plasticity model (CPFEM) for bcc-iron is chosen and is implemented in Abaqus software. This implementation is then validated with the literature. The influence of hydrogen on parameters of this model is also evaluated, allowing for the future coupling of Crystal Plasticity with Hydrogen diffusion. Some very first results in coupled model H-CPFEM are presented
Measurement of Casimir-Polder interaction for slow atoms through a material grating
No full textInternational audienceWe present a method utilizing atomic diffraction patterns and statistical analysis tools to infer the Casimir-Polder interaction between argon atoms and a silicon nitride nanograting. The quantum model that supports the data is investigated in detail, as are the roles of nanograting geometry, finite-size effects, slit width opening angles, Lennard-Jones potentials, and patch potentials. Our findings indicate that the atom-surface potential strength parameter is C3=6.9±1.2meVnm3. This value is primarily constrained by the knowledge of the nanograting geometry. The high sensitivity of our method paves the way for precise determination of the Casimir-Polder potential and exploration of new short-distance forces
Rendre visible la construction sociale de l’espace par la méthode Topino
No full textInternational audienceLa méthodologie Topino sert à rendre visible des constructions sociales des espaces par la représentation des rôles assignés aux femmes et aux hommes.Nous présentons deux approches pour lesquelles cette méthodologie permet un comptage selon une lecture genrée, qui permet de rendre visibles des dynamiques spatiales et sociales. Dans le premier cas, l’accent est mis sur la socialisation de l’observateurice et sa subjectivité face aux rôles socio-sexués performés dans l’espace public. Dans le second cas, l’analyse se concentre sur la socialisation des producteurices d’images — photoreporters ou créateurs et créatrices de signalétique (communication, graphisme), qui sont également pris·es dans des normes sociales et des cadres de représentation propres à leur métier
