Spatially Structured Sparse Morphological Component Separation for Voltage-Sensitive Dye Optical Imaging

International audienceBackground. Voltage-sensitive dye optical imaging is a promising technique for studying in vivo neural assemblies dynamics where functional clustering can be visualized in the imaging plane. Its practical potential is however limited by many artifacts. New Method. We present a novel method, that we call "SMCS" (Spatially Structured Sparse Morphological Component Separation), to separate the relevant biological signal from noise and artifacts. It extends Generalized Linear Models (GLM) by using a set of convex non-smooth regularization priors adapted to the morphology of the sources and artifacts to capture. Results. We make use of first order proximal splitting algorithms to solve the corresponding large scale optimization problem. We also propose an automatic parameters selection procedure based on statistical risk estimation methods. Comparison with Existing Methods. We compare this method with blank subtraction and GLM methods on both synthetic and real data. It shows encouraging perspectives for the observation of complex cortical dynamics. Conclusions. This work shows how recent advances in source separation can be integrated into a biophysical model of VSDOI. Going beyond GLM methods is important to capture transient cortical events such as propagating waves

Which fetal growth charts should be used in France? Position of the French College of Obstetricians and Gynecologists (CNGOF)

Objective: To assess which fetal growth charts best describe intrauterine growth in France defined as the ability to classify 10% of fetuses below the 10th percentile (small for gestational age [SGA]) and above the 90th percentile (large for gestational age [LGA]) in the second and third trimesters. Methods: We analyzed five studies on fetal ultrasound measurements using three French data sources. Two studies used second and third trimester ultrasound data from a nationwide birth cohort in 2011 (the ELFE study, N = 13 197 and N = 7747); one study used third trimester ultrasound data from on a nationwide cross-sectional study (the 2016 French National Perinatal Survey, N = 9940); and the last two studies were from the “Flash study” 2014 which prospectively collected ultrasound data from routine visits in the second and third trimesters (N = 4858 and N = 3522). For each study, we reported the percentage of measurements below the 10th percentile or above the 90th percentile, using French, Hadlock's, WHO and Intergrowth (IG) charts. Results: WHO classified 4.7% and 16.3% of fetuses as having an estimated fetal weight (EFW) 90th percentiles in the second trimester compared to 3.3% and 34.7% with IG. The percentage of fetuses in the third trimester with an EFW 90th percentiles, ranged from 9.1% to 9.4% and from 8.0% to 11.1%, respectively, for WHO, and from 3.9% to 4.1% and from 17.3% to 21.6%, respectively, for IG. The WHO and IG charts for head circumference were very similar and performed well. Compared to the WHO charts, the French and Hadlock's charts deviated more frequently from the target percentiles values for EFW and biometric measures. Conclusion: It is recommended to use the WHO charts for the assessment of EFW and ultrasound biometric measurements in France (strong recommendation; low quality of evidence)

Antiretroviral drug exposure in pregnancy and risk of congenital anomalies: a European case/non-case malformed study

PurposeAntiretroviral drugs are recommended during pregnancy to achieve HIV viral suppression and reduce mother-to-child transmission. Congenital anomaly signals were reported after fetal exposure to antiretroviral drugs in several studies warranting further investigation. We aimed to evaluate the risk of congenital anomalies after fetal exposure to antiretroviral drugs using the European congenital anomaly registry data.MethodsA case/non-case study was performed, using the EUROmediCAT central database. All the congenital anomalies, exposed to any antiretroviral drugs, were included from 1995 to 2019. We explored each signal identified from the literature for associations between congenital anomalies and specific antiretroviral exposures. We compared antiretroviral exposure between the signal anomalies (cases) and all other malformed registrations (controls). Reporting odds ratio (ROR) and their 95% confidence intervals were estimated and adjusted for registry and maternal age.ResultsBetween 1995 and 2019, 173 cases of congenital anomalies were observed after any exposure to antiretroviral drugs. The signal previously identified in the literature between congenital heart defects and exposure to zidovudine was confirmed in the main analysis (aROR 3.66 [1.63–8.23]). Other signals identified in the literature were not confirmed, although two cases of hypospadias and two cases of limb defects were reported after zidovudine and atazanavir exposure, respectively. The signal detection analysis did not reveal any new signal after applying the Bonferroni correction.ConclusionsOur study does not reveal new signals but confirms the previously identified signal between congenital heart defects and fetal exposure to zidovudine. The physio-pathological hypothesis induced by zidovudine exposure should be explored in future studies

Associations between Nitric Oxide Synthase Genes and Exhaled NO-Related Phenotypes according to Asthma Status

International audienceBACKGROUND: The nitric oxide (NO) pathway is involved in asthma, and eosinophils participate in the regulation of the NO pool in pulmonary tissues. We investigated associations between single nucleotide polymorphisms (SNPs) of NO synthase genes (NOS) and biological NO-related phenotypes measured in two compartments (exhaled breath condensate and plasma) and blood eosinophil counts. METHODOLOGY: SNPs (N = 121) belonging to NOS1, NOS2 and NOS3 genes were genotyped in 1277 adults from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Association analyses were conducted on four quantitative phenotypes: the exhaled fraction of NO (Fe(NO)), plasma and exhaled breath condensate (EBC) nitrite-nitrate levels (NO2-NO3) and blood eosinophils in asthmatics and non-asthmatics separately. Genetic heterogeneity of these phenotypes between asthmatics and non-asthmatics was also investigated. PRINCIPAL FINDINGS: In non-asthmatics, after correction for multiple comparisons, we found significant associations of Fe(NO) levels with three SNPs in NOS3 and NOS2 (P ≤ 0.002), and of EBC NO2-NO3 level with NOS2 (P = 0.002). In asthmatics, a single significant association was detected between Fe(NO) levels and one SNP in NOS3 (P = 0.004). Moreover, there was significant heterogeneity of NOS3 SNP effect on Fe(NO) between asthmatics and non-asthmatics (P = 0.0002 to 0.005). No significant association was found between any SNP and NO2-NO3 plasma levels or blood eosinophil counts. CONCLUSIONS: Variants in NO synthase genes influence Fe(NO) and EBC NO2-NO3 levels in adults. These genetic determinants differ according to asthma status. Significant associations were only detected for exhaled phenotypes, highlighting the critical relevance to have access to specific phenotypes measured in relevant biological fluid

Antenatal detection of fetal growth restriction in France : evaluation, determinants and impact on perinatal outcomes

Le retard de croissance intra-utérin (RCIU) est une complication responsable d’une importante mortalité et morbidité périnatales. Son dépistage représente un enjeu important de la surveillance prénatale. Les objectifs de la thèse étaient d’évaluer la performance du dépistage anténatal du RCIU, d’identifier ses déterminants et de mesurer son impact sur les issues périnatales. Dans une première partie, nous avons utilisé les données de l’Enquête Nationale Périnatale de 2010 (N=14 100 enfants uniques) : 21,7% des enfants de poids <10ème percentile étaient suspectés avec un RCIU en anténatal tandis que la moitié des enfants suspectés avait un poids normal à la naissance (faux positifs). Le risque de naissance induite était élevé en cas de suspicion, indépendamment de l’existence d’un faible poids, suggérant des interventions iatrogènes. Les issues néonatales n’étaient pas différentes selon la suspicion. Dans une seconde partie, nous avons utilisé les données d’une cohorte nationale d’enfants nés avant 32 SA en 2011, EPIPAGE 2 (N=3698 enfants uniques sans anomalie congénitale). La prise en charge active pour indication fœtale en cas de RCIU était initiée à partir de 26 SA. Pour 14% des enfants, il existait une discordance entre la suspicion d’un RCIU en anténatal et un faible poids à la naissance. En cas de discordance, le poids de naissance était le paramètre le plus important pour évaluer le pronostic néonatal. Nos travaux soulèvent des questions sur l’efficacité du dépistage du RCIU en France. Ils montrent la nécessité de développer de nouvelles stratégies de dépistage et de poursuivre les recherches pour mesurer leur impact sur les décisions médicales et sur la santé.Fetal growth restriction (FGR) is a pregnancy complication that is responsible for significant perinatal mortality and morbidity. Screening for FGR is a key component of prenatal care. The objectives of this thesis were to evaluate the performance of prenatal screening for FGR, to identify the determinants of antenatal suspicion of FGR and to measure its impact on perinatal outcomes. For the first part of the thesis, we used data from the nationally representative French National Perinatal Survey of births (N=14,100 singleton pregnancies): 21.7% of infants with a low birthweight <10th percentile were suspected with FGR during pregnancy and half of infants suspected with FGR had a normal birthweight (false positives). The risk of indicated delivery was higher when FGR was suspected, regardless of the existence of low birthweight, suggesting possible iatrogenic effects. Outcomes were not different for suspected versus unsuspected low birthweight infants. In the second part of the thesis, we used data from the EPIPAGE 2 national cohort of children born before 32 weeks of GA in 2011 (N=3698 singleton non-anomalous infants). Active management for fetal indications in cases of suspected FGR was initiated at 26 weeks. Antenatal and postnatal assessments of FGR were discordant for 14% of infants. When assessments were discordant, birthweight was a better predictor of adverse neonatal outcome. Our results raise questions about the effectiveness of screening strategies for FGR in France. New strategies for the detection of FGR are needed as well as research to measure the impact of screening on medical decisions and health

Facteurs associés à la réussite d’une tentative voie basse après une césarienne : une étude observationnelle rétrospective monocentrique

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Higher evolutionary dynamics of gene copy number for Drosophila glue genes located near short repeat sequences

Abstract Background During evolution, genes can experience duplications, losses, inversions and gene conversions. Why certain genes are more dynamic than others is poorly understood. Here we examine how several Sgs genes encoding glue proteins, which make up a bioadhesive that sticks the animal during metamorphosis, have evolved in Drosophila species. Results We examined high-quality genome assemblies of 24 Drosophila species to study the evolutionary dynamics of four glue genes that are present in D. melanogaster and are part of the same gene family - Sgs1, Sgs3, Sgs7 and Sgs8 - across approximately 30 millions of years. We annotated a total of 102 Sgs genes and grouped them into 4 subfamilies. We present here a new nomenclature for these Sgs genes based on protein sequence conservation, genomic location and presence/absence of internal repeats. Two types of glue genes were uncovered. The first category (Sgs1, Sgs3x, Sgs3e) showed a few gene losses but no duplication, no local inversion and no gene conversion. The second group (Sgs3b, Sgs7, Sgs8) exhibited multiple events of gene losses, gene duplications, local inversions and gene conversions. Our data suggest that the presence of short “new glue” genes near the genes of the latter group may have accelerated their dynamics. Conclusions Our comparative analysis suggests that the evolutionary dynamics of glue genes is influenced by genomic context. Our molecular, phylogenetic and comparative analysis of the four glue genes Sgs1, Sgs3, Sgs7 and Sgs8 provides the foundation for investigating the role of the various glue genes during Drosophila life