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

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

Maternal and neonatal outcomes associated with induction of labor after one previous cesarean delivery: A French retrospective study

International audienceBackground: The safety of methods of labor induction in women with previous cesarean deliveries is still debated. We investigated perinatal outcomes associated with labor induction among women with a trial of labor after one cesarean delivery. Methods: This retrospective study included 339 women with a trial of labor after one prior cesarean and a singleton term fetus in cephalic presentation in 2013-2016 in a French maternity unit. Labor induction was performed with oxytocin, artificial rupture of membranes and/or prostaglandin E2, according to the Bishop score. The primary outcome was a composite of uterine rupture, low Apgar score, neonatal resuscitation or admission to a neonatal unit. The secondary outcomes included cesarean delivery after onset of labor, postpartum hemorrhage and maternal hospital stay after delivery. We used logistic regression to estimate odds ratios adjusted (aOR) for potential confounders. Results: In our sample, 67.3% of women had spontaneous labor and 32.7% were induced. More than half of the women received oxytocin during labor regardless of the mode of labor. The proportions of the composite outcome and of cesarean after onset of labor were higher in the induced group compared to the spontaneous group (26.1% vs 15.8%, p = 0.02 and 45.0% vs 27.6%, p<0.01, respectively). There were 9 uterine ruptures (2.6%) and this proportion was higher in the induced group compared to the spontaneous group, although this difference was not statistically significant (3.6% vs 2.2%, p = 0.48). After adjustment, labor induction was associated with higher risks of the composite outcome (aOR = 2.45, 95% CI: 1.29-4.65), cesarean after onset of labor (aOR = 2.06, 95% CI: 1.15-3.68) and maternal hospital stay after delivery ≥6 days (aOR = 6.20, 95% CI: 3.25-11.81). No association was found with postpartum hemorrhage. Conclusion: Labor induction after one prior cesarean was associated with a higher risk of adverse perinatal outcome. Nevertheless, the higher proportion of uterine rupture did not differ significantly from that in the spontaneous labor group

Does the Presence of Risk Factors for Fetal Growth Restriction Increase the Probability of Antenatal Detection? A French National Study

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Does the Presence of Risk Factors for Fetal Growth Restriction Increase the Probability of Antenatal Detection? A French National Study

International audienc

Does the Presence of Risk Factors for Fetal Growth Restriction Increase the Probability of Antenatal Detection? A French National Study

International audienc

World Health Organization fetal growth charts applied in a French birth cohort

International audienceObjective: To evaluate the applicability of World Health Organization (WHO) fetal growth charts for abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) at the second and third trimester ultrasounds in a French birth cohort.Materials and methods: Using the ELFE cohort of live births after 33 weeks' gestation in France in 2011, we selected 7747 singletons with fetal biometric measurements at the second (20-25 weeks) and third (30-35 weeks) trimester routine ultrasounds. We calculated proportions of fetuses 90 th and >97 th percentiles for AC, FL and EFW using WHO charts and two international (Intergrowth and Hadlock) and two national (Salomon and CFEF) charts. Analyses were also carried out in a subsample of 4427 low-risk births.Results: WHO charts classified 2-3% and 8-10% of fetuses 97 th and >90 th percentile in both trimesters. Hadlock and CFEF charts also provided a good fit for third-trimester EFW 90 th and >97 th percentiles. Proportions were slightly lower for low-risk pregnancies.Conclusion: WHO charts provided a good description of the distribution of French fetal biometric measures. Further research is needed to assess the impact of using WHO charts on obstetrical management and perinatal outcomes