A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

The Syntax of Nafara DP

This study provides a syntactic analysis of the Senufo Nafara Determiner Phrase. It aims at investigating two major questions that are the status of definite markers, and the underlying structure and derivations leading to the surface word order [N AP Def Dem Num] observed in the language. I argue that the (indefinite) markers occurring in DPs are clitics attaching to the rightmost AP element, and spelling out the fused heads of several functional categories (gender, number, definiteness, and possibly others). In a cartographic approach to DP structure, I argue in favor of multiple Functional Projections occurring above NP. More particularly, I consider AP, DemP, and NumP as their own FPs in which adjectives, demonstratives, and numerals are all functional heads. While A and Dem show overt agreement in definiteness, gender, and number, cardinals do not. I argue that the surfacing word order is the result of roll-up movement with pied-piping, motivated and limited by agreement. Phrasal movement only occurs when required for agreement purposes, and more particularly in order to check uPhi features (and therefore EPP features). For that reason, numerals do not participate in movement, and surface in phrase-final position

Analysing the effects of cover crops on emergence rates and vigor, seedling establishment and verticillium wilt development of sunflower varieties

Sunflower (Helianthus Annuus) faces major production challenges in southern-western France. It is mostly grown in hilly areas, in short rotations and after a long fallow period during which soils are left bare. Crop establishment issues and fungal attacks are recurrent, causing significant yield losses. The effects of agroecological cover crops (CCs) implementation were assessed on the sunflower emergence rates and vigor, its seedling establishment and on the verticillium wilt development. Four sunflower genotypes were sown in an experimental field, following seven CCs treatments containing diverse mixtures of Fabaceae and Brassicaceae. Ecosystem services provided by these crops families sole or combined were evaluated on the measured variables, in a no-till system and without glyphosate. CCs had a significant impact in this one-year experiment. Weather conditions strongly influenced the decrease in emergence and vigor of sunflower seedlings, as well as the early outbreak of verticillium disease. In general, cover crop residues inhibited seedling emergence by reducing soil-seed contact and depleting the seed reserves. Brassicaceae such as radish and mustard also showed a negative impact on sunflower seedling emergence through allelopathy mechanisms, whereas they reduced verticillium wilt development compared to other treatments. The association with Fabaceae did not allow to conclude on a mutualization of the services provided, except that it possibly diluted the negative effects of Brassicaceae at emergence. A positive correlation between soil mineral nitrogen and verticillium was observed. The hypothesis of an increase in microbial activity weakening the sunflower plants was made. Further studies are needed to understand how Brassicaceae et Fabaceae interact at the different stages of the crop cycle, in order to target and maximize ecosystem services provided by them.M-A

Difficultés diagnostiques de l'asthme du nourrisson par les médecins généralistes de Haute-Normandie (enquête qualitative)

L'asthme du nourrisson défini historiquement comme tout épisode dyspnéique avec sibilants qui se reproduit au moins trois fois avant l'âge de 2 ans et ceci quels que soient l'âge de début, l'existence ou non de stigmates d'atopie et la cause apparemment déclenchante est un diagnostic difficile, entraînant un retard diagnostique. Quelles sont les difficultés que rencontrent les médecins généralistes lors du diagnostic de cette pathologie ? Pour répondre à cette question, j'ai réalisé une recherche qualitative en interrogeant des médecins généralistes de Haute-Normandie à leur cabinet. Ainsi, huit grandes difficultés sont observées : l'incertitude de l'évolution de l'asthme du nourrisson, l'absence de certitude diagnostique, la terminologie variée, l'inquiétude parentale, la formation, le diagnostic préférentiel des formes sévères, le déni du diagnostic et le manque de pratique. Toutes ces difficultés sont responsables d'un frein dans la prise en charge de l'enfant. Des solutions peuvent être imaginées : questionnaire clinique stéréotypé, prendre le temps de bien expliquer aux parents la pathologie pour juguler leur inquiétude, rassurer médecins et parents sur l'évolution de l'asthme du nourrisson et bannir le florilège de terminologie ; un schéma synthétique présentant une bonne démarche diagnostique est proposé. Le diagnostic précoce de l'asthme du nourrisson est important pour une meilleure prise en charge de l'enfant, à court terme et en vue de préserver son capital pulmonaire ; cela permet aussi de faire figurer cet antécédent dans son historique médical.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Cadre institutionnel et contexte de la condition étudiante : un demi-siècle d’évolution:Rapport pour l’Observatoire de la vie étudiante, Paris, OSC

Référence interne : 08027 (IREDU

Cadre institutionnel et contexte de la condition étudiante : un demi-siècle d’évolution: Rapport pour l’Observatoire de la vie étudiante, Paris, OSC

Référence interne : 08027 (IREDU

Bibliothèques et société

Si le rôle social des bibliothèques n\u27est plus à prouver, on constate que l\u27innovation peut naître des différentes manières dont la bibliothèque se positionne par rapport à la société

Bibliothèques et société

Si le rôle social des bibliothèques n\u27est plus à prouver, on constate que l\u27innovation peut naître des différentes manières dont la bibliothèque se positionne par rapport à la société