Brain-shift aware risk map for Deep Brain Stimulation Planning

International audienceIn Deep Brain Stimulation surgery, the efficiency of the procedure heavily relies on the accuracy of the placement of the stimulating electrode. Meanwhile, the effectiveness of the placement is difficult due to brain shifts occurring during and after the procedure. We propose an approach to overcome the limitations of current planning software that ignores brain shift. In particular, we consider the motion of vascular structures in order to reduce risks of dissecting a vessel during the procedure. Facing the difficulty to produce an exact brain shift prediction, we propose to build a brain shift aware risk map which embeds the vascular motion risk. This risk map is extrapolated using simulation from clinical studies that provide statistics on the displacement of anatomical landmarks during the procedure. Risk maps can be directly integrated into automatic path planning algorithms to better predict optimal electrode trajectories. The method relies on a physics-based simulation that takes into account brain deformation, electrode placement, cerebrospinal fluid, and vascular motion. The goal is to reproduce the spread of brain shift situations that are noted in clinical studies. Preliminary results show that it is possible to compute safe electrode trajectories even in case of brain shift and yet optimal regarding the placement within the targeted area

Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain

Vertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into A/B compartments. Until now, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late-replicating region for earlier replication. The two origins overlap with a constitutive or a silent tissue-specific promoter. When inserted side-by-side, these modules advance replication timing over a 250 kb region through the cooperation with one endogenous origin located 30 kb away. Moreover, when inserted at two chromosomal sites separated by 30 kb, these two modules come into close physical proximity and form an early-replicating domain establishing more contacts with active A compartments. The synergy depends on the presence of the active promoter/origin. Our results show that clustering of strong origins located at active promoters can establish early-replicating domains

Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease

Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease–associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Physico-chemistry of suspended matter in the Moselle and its tributaries

Afin de caractériser la physico-chimie des matières en suspension de la Moselle et de ses affluents, ce travail s’est appuyé sur une approche géochimique et minéralogique. Notre étude s’est concentrée sur l’analyse des polluants dans les compartiments dissous et particulaire. Ces études ont notamment permis de déterminer (i) la composition des constituants inorganiques dans les particules et colloïdes du milieu aquatique de la Moselle et d’un de ses affluents : la Fensch, (ii) l’évolution des contributions inorganiques le long de la Moselle et de la Fensch ainsi que leur transfert à la confluence Fensch-Moselle, tout en déterminant les sources principales de contamination, (iii) les associations organo-minérales et l’organisation des agrégats présents et (iv) d’étudier la spéciation de certains éléments par des microanalyses. Ce travail a ainsi permis de mettre en évidence l’importance des matières en suspension, souvent négligées par rapport aux autres compartiments Eau et SédimentsThis work uses geochemical and mineralogical approaches to characterize physical and chemical properties of suspended solids in the Moselle and its tributaries. The study focused on analyzing the pollutants in dissolved and particulate compartments. This allowed (i) the identification of inorganic components composition in particles and colloids in the aquatic environment of the Moselle and one of its tributaries: the Fensch, (ii) the determination of the evolution of inorganic contributions along Moselle and the Fensch and their transfer to the confluence Fensch-Moselle in addition to the determination of main contamination sources, (iii) the identification of organo-mineral associations and the determination of the organization of aggregates, (iv) the analysis of the speciation of some elements by microanalysis. This work highlighted the importance of studying suspended solids that are often neglected compared to water and sediments compartment

Lancement d'un observatoire de l'activité des jeunes médecins généralistes en Champagne-Ardenne

REIMS-BU Santé (514542104) / SudocSudocFranceF