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An international observational study validating gene-expression sepsis immune subgroups
No full textInternational audienceBackground Sepsis gene-expression sub-phenotypes with prognostic and theranostic potential have been discovered. These have been identified retrospectively and have not been translated to methods that could be deployed at the bedside. We aimed to identify subgroups of septic patients at high-risk of poor outcome, using a rapid, multiplex RNA-based test. Methods Adults with sepsis, in the intensive care unit (ICU) were recruited from 17 sites in the United Kingdom, Sweden and France. Blood was collected at days 2–5 (S1), 6–8 (S2) and 13–15 (S3) after ICU admission and analyzed centrally. Patients were assigned into ‘high' and ‘low' risk groups using two models previously developed for the Immune-Profiling Panel prototype on the bioMérieux FilmArray® system. Results 357 patients were recruited (March 2021–November 2022). 69% were male with a median age of 67 years, APACHE II score of 21 and a 30% 90-day mortality rate. The proportions of high-risk patients decreased over the three sampling times (model 1: 53%, 40%, 15% and model 2: 81%, 74%, 37%). In model 1, 90-day mortality was higher in a high-risk group at each time (S1: 35% vs 24%, p = 0.04; S2: 43% vs 20%, p < 0.001; S3: 52% vs 24%, p = 0.007). In model 2, mortality was only significantly different at the second sampling time (S1: 30% vs 27%, p = 0.77; S2: 34% vs 14%, p = 0.002; S3: 35% vs 23%, p = 0.13). Conclusions Gene-expression diagnostics can identify patients with sepsis at high-risk of poor outcomes and could be used to identify patients for precision medicine trials. Registration ISRCTN11364482 Registered 24th September 2020
Aerosol spectral optical properties in the Paris urban area and its peri-urban and forested surroundings during summer 2022 from ACROSS surface observations
No full textInternational audienceAbstract. The complex refractive index (CRI; n−ik) and the single scattering albedo (SSA) are key parameters driving the aerosol direct radiative effect. Their spatial, temporal, and spectral variabilities in anthropogenic–biogenic mixed environments are poorly understood. In this study, we retrieve the spectral CRI and SSA (370–950 nm wavelength range) from in situ surface optical measurements and the number size distribution of submicron aerosols at three sites in the greater Paris area, representative of the urban city, as well as its peri-urban and forested rural environments. Measurements were taken as part of the ACROSS (Atmospheric Chemistry of the Suburban Forest) campaign in June–July 2022 under diversified conditions: (1) two heatwaves leading to high aerosol levels, (2) an intermediate period with low aerosol concentrations, and (3) an episode of long-range-transported fire emissions. The retrieved CRI and SSA exhibit an urban-to-rural gradient, whose intensity is modulated by the weather conditions. A full campaign average CRI of 1.41−0.037i (urban), 1.52−0.038i (peri-urban), and 1.50−0.025i (rural) is retrieved. The imaginary part of the CRI (k) increases and the SSA decreases at the peri-urban and forest sites when exposed to the influence of the Paris urban plume. Values of k > 0.1 and SSA < 0.6 at 520 nm are related to a black carbon mass fraction larger than 10 %. Organic aerosols are found to contribute to more than 50 % of the aerosol mass and up to 10 % (urban), 17 % (peri-urban), and 22 % (forest) of the aerosol absorption coefficient at 370 nm. A k value of 0.022 (370 nm) was measured at the urban site for the long-range-transported fire episode
How and Why Do Multimorbid Patients Decide to Follow Their Multiple Medication Prescriptions? Looking Beyond the Risk–Benefit Scale
No full textInternational audienceCurrent public health guidelines emphasize the necessity to optimize medication prescriptions for multimorbid patients with multiple medications to ensure patient adherence while minimizing harm and waste. Nevertheless, there is limited understanding of how these patients choose to follow their medication regimen. This study aimed to describe the variations in the way patients account for their adherence (and non-adherence) to multiple medications and to draw links between these variations and patients’ socioeconomic status. Twenty semi-structured interviews were conducted with patients aged 47–82 years with cardiovascular disease and multiple medically treated chronic conditions. They were transcribed and analyzed using reflexive thematic analysis. We first describe shared concerns about multiple medication taking and situations of medical uncertainty which arose when patients encounter conflicting medical instructions. We then highlight two overarching approaches through which patients conceptualized following their medical prescriptions. Some patients predominantly deferred the choice of medication to their physicians, while others steered the decision-making process and closely monitored what they were prescribed. These styles reflected different ways of engaging with doctors, dealing with side effects, and evaluating prescriptions and were linked to patients’ socioeconomic status. We discuss our results by borrowing from Hirschman’s theory of voice, exit, and loyalty. Findings argue in favor of better coordinated care to reduce prescription ambiguities and highlight the importance of patients with multimorbidity being given sufficient time and space to voice their concerns.Les directives de santé publique actuelles soulignent la nécessité d'optimiser les prescriptions de médicaments pour les patients multimorbides qui prennent plusieurs médicaments, afin de garantir l'adhésion du patient tout en minimisant les dommages et le gaspillage. Néanmoins, on comprend mal comment ces patients choisissent de suivre leur régime médicamenteux. Cette étude vise à décrire les variations dans la manière dont les patients expliquent leur adhésion (et leur non-adhésion) à plusieurs médicaments et à établir des liens entre ces variations et leur statut socio-économique. Vingt entretiens semi-structurés ont été menés avec des patients âgés de 47 à 82 ans souffrant d'une maladie cardiovasculaire et de plusieurs maladies chroniques traitées médicalement. Ils ont été transcrits et analysés à l'aide d'une analyse thématique réflexive. Nous décrivons tout d'abord les préoccupations communes concernant la prise de plusieurs médicaments et les situations d'incertitude médicale qui sont apparues lorsque les patients ont été confrontés à des instructions médicales contradictoires. Nous mettons ensuite en évidence deux approches globales à travers lesquelles les patients conceptualisent le respect de leurs prescriptions médicales. Certains patients s'en remettaient principalement à leur médecin pour le choix des médicaments, tandis que d'autres dirigeaient le processus de décision et surveillaient de près ce qui leur était prescrit. Ces styles reflètent différentes manières de s'engager avec les médecins, de gérer les effets secondaires et d'évaluer les prescriptions, et sont liés au statut socio-économique des patients. Nous discutons nos résultats en nous inspirant de la théorie de l'engagement de Hirschman (exit, voice and loyalty). Les résultats plaident en faveur d'une meilleure coordination des soins afin de réduire les ambiguïtés des prescriptions et soulignent l'importance pour les patients atteints de multimorbidité de disposer de suffisamment de temps et d'espace pour exprimer leurs préoccupations
Outcome of high-grade B-cell lymphoma compared to other large B-cell lymphoma after CAR-T rescue. A DESCAR-T LYSA study
No full textInternational audienceHigh-grade-B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (double hit [HGBL-DH] or triple hit [HGBL-TH]), or not otherwise specified (HGBL-NOS), are considered to be more aggressive diseases among large B-cell lymphomas (LBCL). CD19-targeting Chimeric Antigen Receptor (CAR) T-cells have changed the prognosis of chemoresistant LBCL. Clinical and pathological data of patients treated for relapsed/refractory LBCL or HGBL in third line or more, all characterized by FISH, were collected from the French DESCAR-T registry. Between January 2018 and November 2022, 228 patients were included across 14 centers, 73 with HGBL (28 HGBL-DH MYC-BCL2, 14 HGBL-TH, 8 HGBL-DH MYC-BCL6, 23 HGBL-NOS) and 155 with non-HGBL. Median follow-up was 18.5 months [95% CI, 14.3-23.4] from the date of infusion. Progression-free survival (PFS) and overall survival (OS) were not significantly different between HGBL and non-HGBL, at respectively 3.2 months [95% CI, 2.8-6.0] vs 4.5 months [95% CI, 3.1-8.7] (p = 0.103) and 15.4 months [95% CI, 5.6-32.4] vs 18.3 months [95% CI, 8.5-NR]. From the date of eligibility, the median OS was inferior for patients with HGBL-TH/DH MYC-BCL2 at 6.6 months vs 18.5 months for HGBL-NOS vs 13.6 months for HGBL-DH MYC-BCL6 vs 11.8 months for LBCL (p = 0.037). However, infused patients presented the same outcome. CAR T-cell therapy used in third line or more seems to overcome the poor prognosis of HGBL subtypes, especially in HGBL-TH/DH MYC-BCL2. This observation supports considering the potential benefit of using CAR-T earlier in the course of the disease
Promising multi-component cubic alloys for hydrogen storage: Insights from first-principles calculations and machine learning
No full textInternational audienceAn extensive exploration of the chemical space was conducted to design and identify promising multi-component cubic alloys with appropriate enthalpy of reaction for hydrogen storage applications. We aim to identify alloys with suitable hydrogen absorption conditions for ambient conditions, according to favorable thermodynamic criteria, while addressing computational challenges in modeling large-scale systems. 18 elements were selected, leading to the systematic investigation of over 8,000 quinary alloy systems across four distinct crystal phases (within solid-solution alloys, mono-and dihydrides). This effort resulted in a comprehensive dataset of more than 34,000 equimolar M H x structures, where M represents a combination of 5 elements chosen among the 18 selected atoms. To handle the computational demands of Density Functional Theory (DFT) calculations on such a large scale of disordered supercells, designed by the Special Quasirandom Structure (SQS) method, a Machine Learning (ML) approach 1 was introduced to accurately predict the enthalpy of hydride formation. By training the ML model on a strategically chosen subset of the data, high predictive accuracy was achieved while significantly reducing computational costs. By applying filtering parameters constrained by thermodynamic considerations, such as the value of plateau pressure or the presence of a single plateau, the integrated DFT-SQS-ML framework successfully identified 568 quinary alloy systems as ideal candidates for hydrogen storage. The findings establish a solid foundation for experimental validation and further advancements in the field of hydrogen storage materials
Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection
No full textInternational audienceIn 2005-2006, a chikungunya epidemic of unprecedented magnitude hit Reunion Island, which raised a public health concern through the substantial proportions of long-lasting manifestations. To understand the pathophysiology underlying chronic chikungunya (CC), we designed the CHIKGene cohort study and collected blood samples from 133 subjects diagnosed with CC and from 86 control individuals that had recovered within 3 months, 12-to-15 years after exposure.We conducted bulk RNAseq analysis on peripheral blood mononuclear cells to find differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) and gene ontologies to uncover top-level enriched terms associated with DEGs, and weighted gene correlation network analysis (WGCNA) to elucidate underlying cellular processes.Among 1549 DEGs, gene expression analysis identified 10 top genes including NR4A2 and TRIM58 (upregulated in CC), IGHG3 and IGHV3-49 (downregulated in CC) linked to immune regulation, OSBP2 (upregulated in CC) and SEMA6B (downregulated in CC) linked to neuronal homeostasis and axon guidance, respectively. GSEA and WGCNA unveiled cellular processes such as "Metabolism of RNA" and "Cell Cycle”.This study uncovers a shift in gene expression of CC subjects. IGHG3 and IGHV3-49 gene shut-offs spotlight the importance of neutralizing antibodies against chikungunya virus in the progression to chronic disease. Human diseases associations highlight connections to rheumatoid arthritis, nervous and cardiac systems. GSEA and WGCNA bounce the hypotheses of a persistent viral reservoir or an increased susceptibility to RNA viral pathogens with new onset infections. Together, our findings might offer potential targets for therapeutic options aimed at alleviating chronic chikungunya
The Role of Paraglacial and Periglacial Processes in Shaping Glacial Valleys: Example from NW Iceland
No full textInternational audienceAre U-shaped valleys, long regarded as the exclusive result of glacial erosion, significantly shaped by processes occurring during interglacial periods? This study challenges conventional glacial geomorphology by quantifying the sedimentary contributions of interglacial sequences.Focusing on the Nesdalur valley in Iceland's Westfjords—a U-shaped valley sculpted by repeated glaciation-deglaciation cycles and marked by its Tertiary basalt structure—we investigate the role of slope dynamics. The valley’s geomorphological evolution is analyzed through a volumetric approach using high-resolution (2m x 2m) Digital Elevation Models (DEM) to estimate sediment production from paraglacial rock-slope failures (RSFs) and periglacial scree over the current interglacial period.Our results show that interglacial processes, including slope retreat driven by 11 identified RSFs, have contributed between 1% and 4% of the valley's present volume: mainly paraglacial RSF (68%) and periglacial scree (32%). By extrapolating these data, we estimate that approximately 22 interglacial periods could account for up to 48% of the valley’s denudation. While glacial activity remains essential for sediment evacuation, this study highlights the substantial sedimentary impact of interglacial sequences in valley widening.These findings advocate for a more integrative understanding of U-shaped valleys, positioning interglacial sedimentary dynamics as key drivers of valley morphology. By quantifying the sedimentary contributions of interglacial sequences, this research highlights the complementary roles of glacial and interglacial processes in shaping valleys
Value of tacrolimus 0.1% in the treatment of vitiligo in the era of targeted therapy
No full textInternational audienceBackground: Vitiligo, a prevalent depigmenting condition, affects both adults and children, significantly impacting their quality of life. The standard treatment approach involves the application of topical corticosteroids in conjunction with narrow-band ultraviolet B (UVB) phototherapy. A novel topical treatment, ruxolitinib (a Janus kinase inhibitor), has recently received approval. Notwithstanding the absence of marketing authorization for this particular indication in France, numerous practitioners have adopted the use of tacrolimus ointment 0.1% for the treatment of vitiligo, frequently in conjunction with phototherapy. The objective of this study is to present the benefit/risk ratio of tacrolimus in the treatment of vitiligo.Methods: A comprehensive literature search was conducted by the Centre of Evidence (CDP) of the French Society of Dermatology (SFD) to ascertain the efficacy and safety of topical calcineurin inhibitors (TCIs) in vitiligo. The search strategy encompassed meta-analyses (MAs) and prospective multicentric cohort studies.Results: Literature data - in particular three meta-analyses and one randomised controlled trial - confirm the superiority of tacrolimus versus placebo and its non-inferiority versus super-potent topical corticosteroids. In a subgroup analysis, tacrolimus suggests superior efficacy in children and in facial vitiligo. The combined use of tacrolimus and phototherapy exhibited synergistic efficacy.Conclusion: Notwithstanding the market access of topical ruxolitinib, tacrolimus remains a viable treatment option for vitiligo, as substantiated by extant efficacy and safety in the literature. A recent decision of the French National Agency for the Safety of Medicines and Health Products (ANSM) authorized the compassionate prescription of tacrolimus and its reimbursement for patients
Questioning normality: a study of wavelet leaders distribution
No full textThe motivation of this article is to estimate multifractality classification and model selection parameters : the first-order scaling exponent c 1 and the secondorder scaling exponent (or intermittency coefficient) c 2 . These exponents are built on wavelet leaders, which therefore constitute fundamental tools in applied multifractal analysis. While most estimation methods, particularly Bayesian approaches, rely on the assumption of log-normality, we challenge this hypothesis by statistically testing the normality of log-leaders. Upon rejecting this common assumption, we propose instead a novel model based on log-concave distributions. We validate this new model on well-known stochastic processes, including fractional Brownian motion, the multifractal random walk, and the canonical Mandelbrot cascade, as well as on real-world marathon runner data. Furthermore, we revisit the estimation procedure for c 1 , providing confidence intervals, and for c 2 , applying it to fractional Brownian motions with various Hurst indices as well as to the multifractal random walk. Finally, we establish several theoretical results on the distribution of log-leaders in random wavelet series, which are consistent with our numerical findings.</div
Le mémoire professionnel : un projet collaboratif de professionnalisation transformative
No full textInternational audienceNotre recherche s’inscrit dans le cadre de la formation en alternance de niveau master, où le mémoire professionnel valide les compétences acquises en sciences de gestion. Un point aveugle des dispositifs d’accompagnement concerne l’impact transformateur de ces compétences pour les entreprises.Nous proposons d’analyser le partenariat entre étudiant.e, université/école et institution/entreprise à travers la construction du mémoire, en valorisant ses bénéfices économiques et sociétaux. Mobilisant les principes d’une recherche collaborative, nous intégrons divers acteurs (universités, entreprises, institutions) pour produire des connaissances appliquées et favoriser des changements organisationnels durables.Si l’apprentissage transformatif de l’alternance est reconnu pour les étudiant.es, et que le mémoire nourrit aussi les enseignants, son apport aux institutions/entreprises reste peu étudié. Nous suggérons qu’un cadre collaboratif structuré pourrait renforcer cet impact.Notre analyse repose sur trois axes : le rôle transformateur du mémoire pour l’étudiant.e, l’évaluation des compétences en recherche et leur mise en œuvre, et la recherche collaborative comme levier organisationnel. Pour cela, nous avons encadré trois cohortes en master GRH, en leur proposant d’auto-évaluer leurs compétences, formaliser des preuves et les valider avec enseignant.es et professionnel.les