Artificial Intelligence-Assisted Diagnosis of an Unusual Cause of Periodic Epistaxis : A Case Report

International audienceEpistaxis is a common cause of consultation in otolaryngology, manifesting either as isolated episodes or recurrent events. In this paper, we report the history of an 8-year-old African male who presented with periodic epistaxis temporally associated with joint inflammation. The diagnostic work-up, supported by artificial intelligence-based clinical decision support, led to the diagnosis of rheumatic fever. This case describes a very rare etiology of periodic epistaxis and demonstrates the potential usefulness of artificial intelligence as an adjunctive clinical tool. To our knowledge, this is the first reported case of rheumatic fever presenting with periodic epistaxis in the pediatric population

Application de méthode causale pour l'analyse multi-modèles des interactions entre atmosphère, océan et biogéochimie marine et leur évolution dans les scénarios climatiques

Marine ecosystems play a crucial role in the climate system as well as in human activities (e.g., fishing, tourism). However, projections of their dynamics under climate change remain uncertain due to significant inter-model dispersion, particularly pronounced in the Subpolar North Atlantic, a region characterized by substantial phytoplankton blooms.Primary productivity results from a cascade of interactions. The atmosphere influences vertical mixing and horizontal advection, which in turn alter the availability of essential nutrients for productivity. However, each model differs in its design: grid choices, represented processes, and parameterization. After observing the dispersion of primary productivity (NPP) projections in terms of values, a question arises: is the cascade of interactions the same in each model? Is the role of vertical mixing consistent across models? Does horizontal advection play an emerging role under climate change?This thesis proposes a novel causality-based approach to analyze inter-model differences. After defining a conceptual framework grouping key variables to study NPP variability, we apply PCMCI+, a recently developed causal inference method, to analyze differences in causal relationships.The study first focused on pre-industrial simulations, where a model consensus was observed on the role of winter mixed-layer depth in nitrate and silica availability at bloom initiation. Greater disparity was noted for iron. The role of horizontal nutrient transport is much more variable. Causal links have weaker intensities compared to vertical mixing, with many dynamics specific to each model. Finally, stratification during the bloom also appears as a major inhibiting factor for NPP in 2 out of 5 models (IPSL-CM6A-LR, UKESM1-0-LL).This initial study highlights the advantages of a causality-based intercomparison method, as quantifying links within an interaction cascade provides results that a more traditional intercomparison (e.g., statistical analysis, map visualization, correlation analysis) cannot offer. Certain limitations are also discussed, particularly the trade-off in the number of variables: including too many reduces algorithm performance, but omitting key variables can be detrimental.To analyze the temporal evolution of links, historical simulations and three climate scenarios were studied using 100-year sliding windows. The same method was applied to pre-industrial simulations to obtain a reference distribution of link intensities. This approach reveals three types of changes: • Links intensifying beyond the pre-industrial distribution. This is the case for the nutrient-productivity link in 2 models (CanESM5-CanOE, IPSL-CM6A-LR), where nutrient dependence increases under the scenarios. • Links that disappear or decrease in intensity. For example, the CMCC-ESM2 model shows a declining influence of nutrients on productivity. • Links emerging under climate change. In CESM2, which initially showed no significant influence of spring stratification on productivity, a new link emerges under climate change. Similarly, in IPSL-CM6A-LR, horizontal transport emerges as a compensatory factor for the decreasing influence of vertical mixing.This study opens numerous perspectives, discussed in the final chapter, such as model evaluation or application to other conceptual frameworks.Les écosystèmes marins jouent un rôle important dans le système climatique ainsi que pour les activités humaines (e.g. pêche, tourisme). Cependant, les projections de leur dynamique sous changement climatique restent incertaines en raison d'une importante dispersion inter-modèle, particulièrement prononcée dans l'Atlantique Nord Subpolaire, une région caractérisée par d'importantes floraisons phytoplanctoniques.La productivité primaire résulte d'une cascade d'interactions. L'atmosphère influence le mélange vertical et l'advection horizontale, qui altèrent à leur tour la disponibilité en nutriments essentiels à la productivité. Or, chaque modèle diffère par sa conception: sur les choix de grilles, de processus à représenter et de paramétrisation. Après avoir observé la dispersion des projections de la productivité primaire (NPP) en terme de valeurs, une question émerge : la cascade d'interactions est-elle la même dans chaque modèle ? Le rôle du mélange vertical est-il similaire d'un modèle à l'autre ? L'advection horizontale joue-t-elle un rôle émergent sous l'influence du changement climatique ?Cette thèse propose une nouvelle approche basée sur la causalité pour analyser les différences inter-modèles. Après avoir défini un schéma conceptuel regroupant les variables clés pour étudier la variabilité de la NPP, nous appliquons PCMCI+, une méthode d'inférence causale développée récemment, pour analyser les différences de relations causales.L'étude s'est d'abord portée sur des simulations pré-industrielles où nous avons pu observer un consensus des modèles sur le rôle de la profondeur de la couche de mélange hivernale pour la disponibilité des nitrates et de la silice à l'initiation de la floraison. Une plus grande disparité a été observée pour le fer. Le rôle des transports horizontaux de nutriments, est lui beaucoup plus variable. Les liens causaux ont des intensités plus faibles que pour le mélange vertical avec beaucoup de dynamiques spécifiques à chaque modèle. Enfin, la stratification pendant la floraison apparaît également comme un facteur inhibant majeur de la NPP pour 2 modèles sur 5 (IPSL-CM6A-LR, UKESM1-0-LL).Cette première étude a pu mettre en évidence les avantages d'une méthode d'intercomparaison par la causalité, la quantification des liens dans une cascade d'interactions étant un résultat qu'une intercomparaison plus classique (e.g. analyse statistique, visualisation de carte, analyse par corrélation) ne peut fournir. Certaines limitations sont aussi discutées notamment le compromis à trouver sur le nombre de variable. Ne pas mettre trop de variables pour ne pas diminuer les performances de l'algorithme mais ne pas oublier certaines variables clefs.Ensuite, pour analyser l'évolution temporelle des liens, des simulations historiques et trois scénarios climatiques sont étudiés via des fenêtres glissantes de 100 ans . La même méthode est appliquée à la simulation pré-industrielle pour obtenir une distribution de référence des intensités des liens. Cette approche révèle trois types de changements : • Des liens s'intensifiant atteignant des valeurs au-delà de la distribution pré-industrielle. C'est le cas pour le lien nutriments-productivité pour 2 modèles (CanESM5-CanOE, IPSL-CM6A-LR) où la dépendance aux nutriments s'accroit sous les scénarios. • Des liens qui disparaissent ou diminuent en intensité. Par exemple, le modèle CMCC-ESM2 montre une influence décroissante des nutriments sur la productivité. • Des liens émergents sous changement climatique. Le CESM2, initialement sans influence significative de la stratification printanière sur la productivité, a un lien émergent sous changement climatique. Aussi, le transport horizontal émerge dans l'IPSL-CM6A-LR comme facteur compensatoire de la diminution d'influence du mélange vertical.Cette étude ouvre de nombreuses perspectives qui sont discutées dans le chapitre final comme l'évaluation de modèle ou l'application a d'autres schémas conceptuels

Managing drought stress in wheat ( Triticum aestivum L.) production: strategies and impacts

International audienc

Singular walks in the quarter plane and Bernoulli numbers

We consider singular (aka genus 0) walks in the quarter plane and their associated generating functions $Q(x, y, t)$, which enumerate the walks starting from the origin, of fixed endpoint (encoded by the spatial variables $x$ and $y$) and of fixed length (encoded by the time variable $t$). We first prove that the previous series can be extended up to a universal value of $t$ (in the sense that this holds for all singular models), namely $t = 1/2$ , and we provide a probabilistic interpretation of $Q(x, y, 1/2)$. As a second step, we refine earlier results in the literature and show that $Q(x, y, t)$ is indeed differentially transcendental for any $t \in (0, 1/2]$. Moreover, we prove that $Q(x, y, 1/2)$ is strongly differentially transcendental. As a last step, we show that for certain models the series expansion of $Q(x, y, 1/2)$ is directly related to Bernoulli numbers. This provides a second proof of its strong differential transcendence

Evaluer la flexibilité de signification et de contexte des signaux communicatifs chez les animaux non-humains

International audienceThe concept of flexibility in communication is central to reconstructing the evolutionary history of language, and grappling with “contextual flexibility” in particular is pivotal to address implications for pragmatics‐first accounts of language evolution. Despite significant advances in the field, research is hindered by definitional inconsistencies and methodological gaps across modalities. We build on recent frameworks to propose further, detailed methods for studying contextual and functional variability, incorporating modality‐agnostic and standardised terminology to facilitate cross‐species comparisons. Our approach includes a detailed classification of communicative contexts and outcomes, offering practical methods to disentangle context from function and meaning. By integrating insights across behavioural ecology and comparative psychology, we aim to enhance the comparability of findings and provide a robust foundation for exploring the evolutionary trajectory of communicative flexibility and pragmatics

Effect of a 1-month methotrexate delay on pneumococcal vaccine immunogenicity and disease control in patients with early rheumatoid arthritis (VACIMRA): an open-label randomised trial

International audienceBackgroundPneumococcal vaccination is recommended for patients with rheumatoid arthritis. Because immunosuppressant therapies for rheumatoid arthritis hinder vaccine efficacy, vaccination should be administered before initiating immunosuppressive drugs. We aimed to compare humoral responses in patients with rheumatoid arthritis receiving the pneumococcal 13-valent conjugate vaccine (PCV13) before methotrexate initiation or simultaneously.MethodsIn this randomised, multicentre, open-label trial, patients were recruited from 26 rheumatology departments in 22 university hospitals and four general hospitals in France. Adult patients (aged 18–80 years) with active rheumatoid arthritis (Disease Activity Score in 28 joints >3·2), who were naive to targeted disease-modifying anti rheumatic drugs (DMARDs), had not had methotrexate or leflunomide in the past 3 months, and had no previous pneumococcal vaccinations were included. Patients were excluded in case of treatment with methotrexate or with leflunomide within the previous 3 months and absolute or relative contraindications to methotrexate. Patients were vaccinated with PCV13 at randomisation, before being randomly assigned (1:1) to either the immediate group (methotrexate treatment [maximum dose 15 mg per week] initiated at the same time as PCV13 vaccine) or the delay group (methotrexate initiated 1 month after PCV13 vaccine). Randomisation was stratified by sex (self-reported) and DMARD naive status. 2 months later, patients in both groups were vaccinated with the 23-valent pneumococcal polysaccharide vaccine. Humoral responses, disease activity, infections, and adverse events were assessed at baseline and at 1, 3, 6, and 12 months after PCV13. The primary outcome was the responder rate at 1 month, defined by positive responses against at least three of five target serotypes (ie, 1, 3, 5, 7F, and 19A). Responders were defined according to a 2 or more-fold increase in IgG concentrations with ELISA or opsonophagocytic assay compared with baseline. The main analysis was performed in the modified intention-to-treat population, including all randomly assigned patients with a valid measure of the primary endpoint, analysed in their assigned group. There was no involvement of people with lived experience in the study design or implementation. The trial was registered at ClinicalTrials.gov(NCT01942174) and is completed.FindingsBetween Sept 27, 2013, and Oct 10, 2019, 276 patients with rheumatoid arthritis were randomly assigned. 27 patients were excluded, of whom four patients dropped out, and 249 patients were included in the modified intention-to-treat population (126 [51%] in the delay group and 123 [49%] in the immediate group). 174 (70%) patients were female and 75 (30%) were male, the mean age at enrolment was 55·6 years (SD 14·8). Responder rates were higher in the delay group compared with the immediate group for IgG concentrations (relative risk 1·46 [95% CI 1·10–1·92]; p=0·02) and for opsonophagocytic assay activity (1·65 [1·25–2·19]; p=0·01), adjusted for sex and true DMARD naive status. At 12 months, antibody functional activity was significantly higher for eight of 13 serotypes in the delay group. Cumulative doses of corticosteroids and the number of patients who had targeted DMARDs were similar between groups throughout. 72 (11%) of 649 adverse events were serious (including one vaccine-related serious adverse event) in both groups and were equally frequent between groups, and the rheumatoid arthritis disease activity score remained comparable during follow-up.InterpretationIn patients with early rheumatoid arthritis, the PCV13 vaccine administered 1 month before methotrexate allowed for improved immunological responses without significant effect on disease control during one year of follow-up. Future steps are to confirm these results with PCV20 or PCV21 and assess the best time frame for the booster vaccine

Antisense oligonucleotides targeting the SARS-CoV-2 nucleocapsid gene decrease viral titers in hamsters

International audienceSARS-CoV-2 is a positive, single-stranded RNA coronavirus responsible for the COVID-19 pandemic. The emergence of new variants and the limited efficacy of current antivirals demonstrate the need for novel therapeutic strategies. Here, we present the design, screening, and evaluation of antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 genomic and sub-genomic RNA. By employing a combination of luminescence-based reporter assays and quantitative reversetranscription PCR (RT-qPCR) in human cells, we selected ASO-N1, directed against the nucleocapsid RNA, as the best candidate to be validated in vivo. Hamsters infected with SARS-CoV-2 were treated with an initial intranasal ASO dose, followed by daily systemic administration. ASO-treated animals showed significantly improved clinical signs, indicated by increased food consumption and reduced weight loss. ASO-N1 induced a sustained reduction in viral RNA and inflammatory cytokine expression in the nasal mucosa and efficiently decreased infectious viral titers in nasal swabs at day 3 post infection. Further optimization of the ASO-N1 sequence with a combination of RNase-H1-dependent and steric blockage chemistries synergistically increased the antiviral efficacy in vitro. Finally, the target site of ASO-N1 remained completely conserved across all major SARS-CoV-2 variants over the past 4 years, demonstrating the potential of nucleocapsid RNA-targeting ASO as a robust antiviral strategy against SARS-CoV-2

Coupling of X‐AES Transitions and XPS Photopeaks to Assess the Oxide Formation of Ga and in CuIn_0.7Ga_0.3Se₂ Material During Air Aging

International audienceABSTRACTThe solar absorber Cu (In0.7Ga0.3)Se2 (CIGS) undergoes a process of evolution upon exposure to the atmosphere, resulting in the growth of oxide phases. This phenomenon can potentially affect the interfacial properties of CIGS, which in consequence may impact the efficiency of the solar cell. X‐ray photoelectron spectroscopy (XPS) is an appropriate method to analyze the degradation of CIGS upon air aging. However, many photopeaks and Auger lines of the constitutive elements are distributed along the energy scale, and the exact determination of the degradation within the CIGS absorber requires specific care to select peaks to consider to ensure that information arise from similar escape depths. In this study, we propose to investigate the kinetics of degradation of Ga and In at similar depths probed by coupling not only photopeaks but also X‐Auger electron spectroscopy (X‐AES) transitions in the absence of photopeaks in the same energy range. If photopeaks modeling is well established for In and Ga, a decomposition procedure of the X‐AES transitions must be developed. Both linear and nonlinear least square fitting were used and compared, starting to model CIGS, In2O3, and Ga2O3 references to deploy it after on Auger transitions measured on aged samples. Thanks to the determination of the degradation ratios (oxide phase over CIGS phase) at 3, 7, and 9 nm depth, we show that both In and Ga exhibit similar kinetic of oxide formation, which proceeds gradually by O penetration through the subsurface of the material, this penetration being more and more attenuated deeper.</p

Expanded Composite Coral Indices of South Pacific Convergence Zone Oceanographic Variability Since 1848 CE

International audienceAbstract In the South Pacific Convergence Zone (SPCZ), interannual to interdecadal oceanic and atmospheric variability is especially pronounced. The El Niño Southern Oscillation and the Interdecadal Pacific Oscillation significantly influence the SPCZ diagonal axis and salinity front. Regional coral‐based paleo‐environmental reconstructions extend the relatively short and discontinuous instrumental sea surface temperature (SST) and sea surface salinity (SSS) record to elucidate past variability. We present monthly resolved, composite indices of coral skeletal δ 18 O, Sr/Ca, and calculated δ 18 O sw utilizing coral geochemical time‐series from Rotuma, Fiji, Tonga, and Rarotonga, dubbed the SPCZ coral (SPCZ c ) indices. The new indices build upon previous efforts to describe variability and trends in the SPCZ region with expanded coverage due to a new northwestern coral addition from the SPCZ fresh pool. The increased spatial and temporal resolution of the new indices allows for higher‐fidelity sub‐annual reconstructions of SST and SSS in the region dating back to 1848. The results confirm the secular warming trend of 1°C in the SPCZ region and show a 0.4 S p freshening starting in the 1880s. The SPCZ c δ 18 O sw is the first regional reconstruction of δ 18 O sw and provides valuable insights into past SSS variability, including elucidating responses to El Niño and La Niña events, as well as identifying past SPCZ zonal events. The SPCZ c δ 18 O sw reconstruction extends the instrumental records by ∼100 years. The SPCZ c indices prove the utility of the compositing approach in describing regional oceanographic variability with the increased signal‐to‐noise ratio of the obtained coral climatic data

Furosemide and Serum Protein-Bound Uremic Toxin Concentrations in Patients With CKD

International audienceIntroduction: Furosemide is commonly prescribed to patients with chronic kidney disease (CKD) but may impair the kidney's excretion of protein-bound uremic toxins (PBUTs) via the organic anion transporters 1 and 3 (OAT1 and OAT3). We evaluated the association between furosemide prescription (status and dose level) and the serum concentrations of free OAT1/3-inhibiting uremic toxins (UTs) in patients with CKD.Methods: We included 2342 patients with CKD (stages 2-5) from the CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort and with centralized serum UT assay data at baseline. The UTs were assayed using liquid chromatography - tandem mass spectrometry. The OAT1/3-inhibiting UTs identified in a literature review included indoxyl sulphate (IS), kynurenine (Kyn), p-cresyl sulphate (PCS), and indole-3-acetic acid (IAA). Multiple linear regression was used to assess each PBUT or their sum ( ΣUTsfree) as the dependent variable.Results: Patients prescribed furosemide (n = 799, 34%) were older and had a lower estimated glomerular filtration rate (eGFR), a higher C-reactive protein (CRP) concentration, more comorbidities, and more concomitant medications than patients not prescribed furosemide. After adjustment for potential confounders, patients prescribed &gt; 120 mg furosemide had significantly higher serum concentrations of ΣUTsfree (+19.1%), IS (+31.9%), Kyn (+9.3%), PCS (+29.3%), and IAA (+162.9%) than patients not prescribed furosemide. Using a smooth function to model the association between the furosemide dose level and PBUTs, we observed (for ΣUTsfree and each free UT) a steep increase between 80 and 100 mg and then a high plateau.Conclusion: In patients with CKD, furosemide (particularly at a dose level &gt; 120 mg) is independently associated with higher serum free PBUT concentrations. Our findings suggest that drug-UT competition contributes to PBUT accumulation