The NAOMI GAZL multispecies differential absorption lidar: realization and testing on the TADI gas leak simulation facility

International audienceWe report on a differential absorption lidar, designed for remote detection of CH 4 and CO 2 , based on a single-frequency 1.57-1.65 µm parametric oscillator/amplifier system. The lidar is tested on a controlled gas release facility

Projet SELPHUV : personnaliser la prévention solaire au moyen de la photographie UV

Les rayons ultraviolets (UV) solaires sont le principal facteur causal des cancers de la peau (mélanome et cancer épithélial de la peau) et les personnes ayant des activités de loisirs ou professionnelles à forte exposition aux UV courent un risque accru de cancer. Malgré des campagnes de prévention variées et de longue date, l'incidence du cancer de la peau en Suisse continue d’augmenter et reste parmi les plus élevées d'Europe. Ceci suggère que de nouvelles approches de prévention sont nécessaires. Cette étude visait à démontrer la faisabilité et l'acceptabilité d'un service de prévention du cancer de la peau utilisant la photographie UV et des messages de prévention personnalisés, ciblant les groupes ayant une exposition chronique aux UV solaires. Ainsi, 440 personnes dans 13 sites publics et privés répartis dans le canton de Vaud ont rempli un questionnaire électronique pour recueillir des informations sur leurs habitudes de protection au soleil et effectuer une prise de photographie de leur visage. Pour ce faire, l'appareil photo VISIA7 (Canfield®) a été utilisé pour compter et montrer la présence de taches UV et de rides aux participant.e.s. Sur la base de ces données et de la photographie, un message de prévention personnalisé a été délivré sur place par une infirmière formée. Un questionnaire de suivi a été envoyé 3 mois plus tard aux participant.e.s pour évaluer leur satisfaction ainsi qu’un éventuel changement dans leurs habitudes de protection solaire. Les entités visitées ont également répondu à un bref questionnaire de satisfaction quelques mois après la prestation, et montré leur haut degré de satisfaction, et le cas échéant une volonté de faire participer d’autres collaborateurs/élèves/usagers. Les participant.e.s (âge médian 44 ans ; 58% d'hommes ; 52% de travailleuse.eur.s en extérieur) ont, dans l'ensemble, déclaré un niveau relativement élevé de satisfaction avec la prestation. Leur niveau de protection solaire était relativement élevé avant la prestation, en accord avec les études précédentes, allant de 9% de port de manches longues à 72% de port de lunettes de soleil. Une moyenne de 343 taches UV a été mesurée par personne (étendue : 0 à 590 taches). Les principaux déterminants d'un nombre plus élevé de taches UV étaient le fait d'avoir un niveau d'éducation plus élevé, un phototype plus clair, fréquenté le solarium, un nombre d’années plus élevé de travail en extérieur, reçu des coups de soleil dans la jeunesse et pris des bains de soleil. Une majorité des 274 (62% du total) participant.e.s ayant répondu au second questionnaire ont indiqué avoir amélioré leur protection solaire (n=167, 61%). Dans le détail, chaque moyen de protection investigué a été significativement davantage utilisé dans les trois mois suivant la prestation, la plus forte progression étant pour le port de chapeau passant de 54% à 71% tant en loisirs qu’au travail. Cependant, aucun déterminant spécifiquement associé à ces changements positifs n’a pu être identifié. La raison principale perçue par l'individu pour un changement favorable du comportement de protection contre les UV semble être liée au message de protection personnalisé. Toutefois, comme la photographie renforçait le message délivré par les infirmières et que le protocole ne comportait pas de groupes de comparaisons, aucune conclusion définitive ne peut être tirée sur l’impact seul de la photo ou du message. Quant aux raisons de non-changement, outre une protection déjà jugée convenable, les travailleuse.eur.s en extérieur ont souligné l’impossibilité de suivre certaines recommandations dans le cadre professionnel. Quelques pistes d’amélioration générale de la prestation sont proposées. Une analyse financière des conditions de pérennisation de cette prestation complète ce rapport

An empirical resource for discovering cognitive principles of discourse organisation: the ANNODIS corpus

International audienceThis paper describes the ANNODIS resource, a discourse-level annotated corpus for French. The corpus combines two perspectives on discourse: a bottom-up approach and a top-down approach. The bottom-up view incrementally builds a structure from elementary discourse units, while the top-down view focuses on the selective annotation of multi-level discourse structures. The corpus is composed of texts that are diversified with respect to genre, length and type of discursive organisation. The methodology followed here involves an iterative design of annotation guidelines in order to reach satisfactory inter-annotator agreement levels. This allows us to raise a few issues relevant for the comparison of such complex objects as discourse structures. The corpus also serves as a source of empirical evidence for discourse theories. We present here two first analyses taking advantage of this new annotated corpus --one that tested hypotheses on constraints governing discourse structure, and another that studied the variations in composition and signalling of multi-level discourse structures

ANNODIS : une approche outillée de l'annotation de structures discursives

International audienceThe ANNODIS project has two interconnected objectives: to produce a corpus of texts annotated at discourse-level, and to develop tools for corpus annotation and exploitation. Two sets of annotations are proposed, representing two complementary perspectives on discourse organisation: a bottom-up approach starting from minimal discourse units and building complex structures via a set of discourse relations; a top-down approach envisaging the text as a whole and using pre-identified cues to detect discourse macro-structures. The construction of the corpus goes hand in hand with the development of two interfaces: the first one supports manual annotation of discourse structures, and allows different views of the texts using NLP-based pre-processing; another interface will support the exploitation of the annotations. We present the discourse models and annotation protocols, and the interface which embodies them.Le projet ANNODIS vise la construction d'un corpus de textes annotés au niveau discursif ainsi que le développement d'outils pour l'annotation et l'exploitation de corpus. Les annotations adoptent deux points de vue complémentaires : une perspective ascendante part d'unités de discours minimales pour construire des structures complexes via un jeu de relations de discours ; une perspective descendante aborde le texte dans son entier et se base sur des indices pré-identifiés pour détecter des structures discursives de haut niveau. La construction du corpus est associée à la création de deux interfaces : la première assiste l'annotation manuelle des relations et structures discursives en permettant une visualisation du marquage issu des prétraitements ; une seconde sera destinée à l'exploitation des annotations. Nous présentons les modèles et protocoles d'annotation élaborés pour mettre en œuvre, au travers de l'interface dédiée, la campagne d'annotation

Meta-analyses identify DNA methylation associated with kidney function and damage

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms