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The AdaptSgenoLasso, an extended version of the SgenoLasso, for gene mapping and for genomic prediction using the extremes
No full textInternational audienceWe introduce here the AdaptSgenoLasso, a new penalized likelihood method for gene mapping and for genomic prediction, which is an extended version of the SgenoLasso. The AdaptSgeno-Lasso relies on the original concept of a selective genotyping that varies along the genome. The "classical" selective genotyping on which the SgenoLasso is built on, consists in genotyping only extreme individuals, in order to increase the signal from genes. However, since the same amount of selection is applied at all genome locations, the signal is increased of the same proportional factor everywhere. With the AdaptSgenoLasso, we allow geneticists to impose more weights on some loci (i.e. locations) of interest, known to be responsible for the variation of the quantitative trait. The resulting signal is now dedicated to each locus. We propose here a deep theoretical study of the AdaptSgenoLasso, and we show on simulated data the superiority of this new approach over the SgenoLasso
Efficient Biochemical Method for Characterizing and Classifying Related Amyloidogenic Peptides
No full textInternational audienceAmyloidosis is a group of proteinopathies characterized by the systemic or organ-specific deposition of proteins in the form of amyloid fibers. Nearly 40 proteins play a role in these pathologies, and the structures of the associated fibers are beginning to be determined by Cryo-EM. However, the molecular events underlying the process, such as fiber nucleation and elongation, are poorly understood, which impairs developing efficient therapies. In most cases, only a few dozen amino acids of the pathological protein are found in the final structure of the fibers, while amyloid peptides comprising five to 10 amino acids are involved in the fiber nucleation process. The identification and biochemical characterization of these peptides are therefore of major scientific and clinical importance. We demonstrated that in silico approaches are limited due to the peptides’ small size and long-distance intra- and intermolecular interactions that occur during nucleation. To address this problem, we developed a novel biochemical method for characterizing and classifying batches of related peptides. Initial work to optimize our approach is based on the reference peptide PHF6 (β1) from Microtubule-Associated Protein Tau (MAPT) as compared to 22 related peptides. Depending on their biochemical properties and using the Garnier–Delamarche plot we propose, we classified these peptides into three groups: aggregative, amyloid, and soluble (neither aggregative nor amyloid). We emphasize that our biochemical classification method is applicable to any family of peptides and could be scaled up for high-throughput analyses
The effect of pressure on the aluminoborosilicate glass optical basicity
No full textInternational audienceThe glass optical basicity (Λ) is an adequate way of representing a glass composition that has been successfully applied for glasses made under ambient pressure conditions. However, we do not know if the proposed calculation based on the glass structure and the proposed measurement involving the determination of glass refractive index can apply to glasses made under high-pressure conditions.We studied several aluminoborosilicate glass compositions synthesized under high-pressure conditions up to 3 GPa and 1250°C. Recovered glasses were characterized to determine the refractive index (nD) and the density (ρ). The glass structure was determined using 11 B and 27 Al Nuclear Magnetic Resonance. Increasing pressure up to 3 GPa increases nD and ρ for the studied glasses. Change in the glass structure is consistent with previous studies showing an increase in Al coordination, especially for Ca-bearing glass composition; and an increase in the proportion of BO4 species. The glass optical basicity decreases with increasing pressure.From the structural changes, Λ decreases by ~2% from ambient to 1 GPa in pressure for the investigated glass compositions.</p
A biological pharmacology network to secure the risk of drug–drug interaction with nirmatrelvir/ritonavir
No full textInternational audienceNirmatrelvir/ritonavir is a protease inhibitor antiviral drug indicated in the treatment of severe acute respiratory syndrome coronavirus-2 infections in high-risk patients for a severe disease. Unfortunately, ritonavir, used to boost nirmatrelvir pharmacokinetics, can also inhibit or induce the metabolism of other co-administered drugs substrates. This may lead to a subsequent risk of adverse drug reaction and lack of efficacy. In this study, we aimed at describing the expert advices provided by the biological pharmacology network of the SFPT (i.e., the therapeutic drug monitoring specialists working in the laboratories of the pharmacology departments in France/Belgium). From February to August 2022, we collected all specialized advices provided by the biological pharmacology network of the SFPT. Seven pharmacology departments actively participated in the study (Brussels Saint-Luc Hospital in Belgium, Caen, Dijon, Nantes, Nancy, Rennes and Toulouse in France). We collected the following data: patient's age, date of nirmatrelvir/ritonavir initiation, clinical department requiring the expert advice, patient's treatments, and advice provided. One hundred and six expert advice on 753 drugs were provided during the seven months of data collection. Two centers provided 83% of all the expert advice (around 8/month). Patients originated form a transplantation department in 65% of the cases. The most common request were for cardiac drugs (28%), immunosuppressive drugs (24%) and endocrine drugs (18%). The advice were distributed as follows: treatment continuation, treatment discontinuation during the antiviral course, dosage adjustment, and treatment switch in 59%, 28%, 11%, and 1.6% of the cases, respectively. Only 2 pieces of advice (0.3%) constituted treatment contra-indications. Drug monitoring was proposed in 10% of prescription lines. Expert advice provided by the biological pharmacology network of the SFPT allows securing the combination of nirmatrelvir/ritonavir with other concomitant drugs. Most of eligible patients to the antiviral drug can benefit from it despite the risk of drug–drug interaction
Villages en politique. Pouvoirs et sociétés rurales en France (1634-années 1970)
No full textParmi les nombreuses métamorphoses que les campagnes françaises ont connues depuis le XVIIe siècle, la politisation est l’une des plus spectaculaires. Ce numéro spécial de Parlement[s] en prend la mesure. La plupart des pouvoirs sont appréhendés ici : celui de l’État, des seigneurs de l’Ancien Régime, des Églises, des notables et des élus des régimes autoritaires et démocratiques issus de la Révolution, des communautés rurales elles-mêmes et des nombreux acteurs, institutionnels ou informels, qui participent à la « mise en politique » des campagnes. Ce recueil rassemble une vingtaine de sources – textes et images – commentées par des historiennes et historiens spécialistes de ces questions. Comment s’organisent et évoluent, sur la longue durée et à différentes échelles, les multiples modes de domination du sol et des hommes ? Quelles sont les craintes et les attentes des villageois, leurs colères et leurs formes d’adhésion ? Comment agissent-ils, comment s’informent-ils dans des sociétés rurales qui s’alphabétisent, se médiatisent et s’intègrent au sein de l’État nation ? Telles sont les questions auxquelles ces études de cas proposent de répondre.Ce numéro s’inscrit dans le cadre des programmes d’agrégation 2025-2026 en histoire moderne et en histoire contemporaine. Ces documents et leurs commentaires seront aussi très utiles aux collègues de l’enseignement secondaire, qui pourront s’en inspirer dans le cadre de leurs cours
Treatment-free remission in chronic myeloid leukemia with rare ABL1 gene fusions: real-life study from the French CML group Fi-LMC.
No full textInternational audienceTyrosine kinase inhibitors of the BCR::ABL1 oncoprotein can be stopped without subsequent molecular relapse or major safety concerns in 40 to 80% of adult patients with P210BCR::ABL1 positive chronic myeloid leukemia with sustained deep molecular responses. In contrast, ending treatment in patients with rare rearrangements located outside the major BCR region or within the exon 3 of ABL1 remains to be explored. Twenty-four patients with chronic phase disease and diverse uncommon BCR::ABL1 transcripts who obtained sustained molecular residual disease negativity and stopped therapy in a real-life setting for various reasons were retrospectively evaluated for treatment-free remission determinants. Six patients relapsed after a median time of 6 months (range; 3-49), relapse being defined as a rise in molecular residual disease above the 3-log threshold. Treatment-free remission probabilities at 12 and 60 months were 83.3% (95% CI: 68.4-98.2%) and 70.6% (95% CI: 49.5-91.6), respectively. The type of BCR::ABL1 transcript was the only relevant baseline factor associated with durable treatment-free remission and patients with fusions lacking exon a2 sequences had the best outcome. To conclude, treatment-free remission is a reasonably achievable goal in patients with rare ABL1 fusion transcripts. Our results pave the way for recommendations in clinical practice. Nevertheless, further research is needed to determine which patients have highest chances to reach deep molecular response levels and become free from therapy and to decipher the biological impact of the different molecular rearrangements of BCR::ABL1 on treatment-free remission
Elevational range shifts among Bombina toad populations in the Alps in response to future climate change
No full textInternational audienceThe ability of species to cope with climate change depends on both intrinsic and extrinsic factors, for instance dispersal ability and landscape composition. Nevertheless, populations can also differ in their ability to track the shift of suitable areas due to traits developed in response to local environmental pressures. In the south-west part of the distribution area of the yellow-bellied toad (Bombina variegata), two divergent ecotypes, named fast and slow, can be identified along a gradient of anthropization. We investigate the ability of these ecotypes to track the altitudinal shift of suitable habitat in the French Alps at the horizon 2100. First, we modelled future climatic suitability in the Alps according to climatic scenarios, and then we used a process-based model simRShift, to simulate the demographic and colonisation processes in the future accounting for the traits of each ecotype. The fast ecotype may not persist and colonise as many habitats compared to the slow ecotype (e.g. 872.3km2 and 4200.2 km2 under the optimistic scenario in 2100 for the GFDL-ESM4 GCM respectively for fast and slow). We explain these results by the shorter lifespan of the fast ecotype that makes it more vulnerable to stochasticity
Anchoring in Takeovers Under Mandatory Bid Rule: Evidence From an Emerging Market
No full textInternational audienceThis article documents the existence of an anchoring bias in the pricing and acceptance of takeover bids in a blockholder regime where the mandatory bid rule applies. Our analysis, performed on the Romanian market for corporate control, shows that the 52‐week high price of the target and the pricing of direct privatisations conducted by the government are strong predictors of both bid premium and outcome. The tender decision depends also on the scope of expropriation perceived by minority shareholders. Our results suggest that stronger capital market discipline is also important for insuring an effective protection of minority shareholders
Maintaining ventilation with very low tidal volume and positive-end expiratory pressure versus no ventilation during cardiopulmonary bypass for cardiac surgery in adults: a randomized clinical trial
No full textInternational audiencePurpose: Cardiopulmonary bypass (CPB) during cardiac surgery mechanically circulates and oxygenates the blood, bypassing the heart and lungs. Despite limited evidence, maintaining mechanical ventilation (MV) during CPB is recommended, as ventilator strategies during surgery may reduce the occurrence of postoperative infections. We aimed to determine whether maintaining MV for cardiac surgery would decrease postoperative infections compared with stopping MV during CPB.Methods: We conducted a multicenter, single-blind, randomized trial among adult patients undergoing scheduled cardiac surgery with CPB in six hospitals in France. During CPB, the tracheal tube was disconnected from the ventilator in the control group (MV- group). In the MV + group, ventilation was maintained during CPB with very low tidal volume ventilation, using a tidal volume of 2.5 mL/kg of predicted body weight, with 5-7 cmH2O positive end expiratory pressure. The primary outcome was the occurrence of all types of postoperative infections within the first 28 days after surgery. There were six secondary evaluation criteria including the number of days of exposure to antibiotics.Results: A total of 1362 patients were enrolled in the study. Postoperative infection occurred in 74 out of 680 patients (10.9%) in the MV- group, compared to 68 out of 682 patients (10.0%) in the MV + group (relative risk, 0.92; 95% confidence interval [CI] 0.67-1.25; p = 0.58). Antibiotic use was higher in the MV + group than in the MV- group (incidence risk ratio, 1.08; 95% CI 1.02-1.15; p = 0.02). There were no significant differences between the groups for all other secondary outcomes or for the incidence of adverse events.Conclusions: Maintaining very low tidal volume ventilation with positive end-expiratory pressure during CPB did not reduce postoperative infections at 28 days compared to when mechanical ventilation was stopped during CPB. An unexpectedly higher use of antibiotics was observed when ventilation was maintained.Trial registration: ClinicalTrials.gov (NCT03372174