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Background: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe tinnitus in patients with extreme phenotype. Methods: for this extreme phenotype study, we used three different cohorts with European ancestry (Spanish with Meniere disease (MD), Swedes tinnitus and European generalized epilepsy). In addition, four independent control datasets were also used for comparisons. Whole-exome sequencing was performed for the MD and epilepsy cohorts and whole-genome sequencing was carried out in Swedes with tinnitus. Findings: we found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2 (p < 2E 04), when they were compared with reference datasets. This burden was replicated for ANK2 gene in a Swedish cohort with 97 tinnitus individuals, and in a subset of 34 Swedish patients with severe tinnitus for ANK2, AKAP9 and TSC2 genes (p < 2E 02). However, these associations were not significant in a third cohort of 701 generalized epilepsy individuals without tinnitus. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, including membrane trafficking and cytoskeletal protein binding in neurons. Interpretation: a burden of rare variants in ANK2, AKAP9 and TSC2 is associated with severe tinnitus. ANK2, encodes a cytoskeleton scaffolding protein that coordinates the assembly of several proteins, drives axonal branching and influences connectivity in neurons.

We present a numerical study of the time-dependent motion of a two-dimensional vesicle in a channel under an imposed flow. In a Poiseuille flow the shape of the vesicle depends on the flow strength, the mechanical properties of the membrane, and the width of the channel as reported in the past. This study is focused on the centered snaking (CSn) shape, where the vesicle shows an oscillatory motion like a swimmer flagella even though the flow is stationary. We quantify this behavior by the amplitude and frequency of the oscillations of the vesicle's center of mass. We observe regions in parameter space, where the CSn coexists with the parachute or the unconfined slipper. The influence of an amplitude modulation of the imposed flow on the dynamics and shape of the snaking vesicle is also investigated. For large modulation amplitudes transitions to static shapes are observed. A smaller modulation amplitude induces a modulation in amplitude and frequency of the center of mass of the snaking vesicle. In a certain parameter range we find that the center of mass oscillates with a constant envelope indicating the presence of at least two stable states., Comment: 10 pages, 7 figures

International audience; Ageing populations have become a major concern over the past fifty years, drawing the attention of both politics and science. The target of a raft of health and social policies, older people are often identified as a specific, and vulnerable, population. At the same time, ageing has become a specialisation in disciplines such as medicine and sociology, and a discipline of its own: gerontology. Questioning this framing of old age, this book unpacks the politicaland moral dimensions of scientific research on ageing. It brings together a range of multidisciplinary, European perspectives, and will be of use to all those interested in old age and the social sciences.

International audience; This paper presents sufficient conditions for the robust asymptotical stabilization of uncertain descriptor fractional-order systems with the fractional order α satisfying 0 < α < 2. The results are obtained in terms of linear matrix inequalities. The parameter uncertainties are assumed to be time-invariant and norm-bounded appearing in the state matrix. A necessary and sufficient condition for the normalization of uncertain descriptor fractional-order systems is given via linear matrix inequality (LMI) formulation. The state feedback control to robustly stabilize such uncertain descriptor fractional-order systems with the fractional order α belonging to 0 < α < 2 is derived. Two numerical examples are given to demonstrate the applicability of the proposed approach.

The understanding of domain structures, specifically domain walls, currently attracts a significant attention in the field of (multi)-ferroic materials. In this article, we analyze contrast formation in full field electron microscopy applied to domains and domain walls in the uniaxial ferroelectric lithium niobate, which presents a large 3.8 eV band gap and for which conductive domain walls have been reported. We show that the transition from Mirror Electron Microscopy (MEM – electrons reflected) to Low Energy Electron Microscopy (LEEM – electrons backscattered) gives rise to a robust contrast between domains with upwards (Pup) and downwards (Pdown) polarization, and provides a measure of the difference in surface potential between the domains. We demonstrate that out-of-focus conditions of imaging produce contrast inversion, due to image distortion induced by charged surfaces, and also carry information on the polarization direction in the domains. Finally, we show that the intensity profile at domain walls provides experimental evidence for a local stray, lateral electric field.

International audience; This paper introduces an effective Static ProbabilisticTiming Analysis (SPTA) for multi-path programs. The analysis estimates the temporal contribution of an evict-on-miss, random replacement cache to the probabilistic Worst-Case Execution Time (pWCET) distribution of multi-path programs. The analysis uses a conservative join function that provides a proper overapproximation of the possible cache contents and the pWCET distribution on path convergence, irrespective of the actual path followed during execution. Simple program transformations are introduced that reduce the impact of path indeterminism while ensuring sound pWCET estimates. Evaluation shows that the proposed method is efficient at capturing locality in the cache, and substantially outperforms the only prior approach to SPTA for multi-path programs based on path merging. The evaluation results show incomparability with analysis for an equivalent deterministic system using an LRU cache.

Background School is a multi-cultural setting where students need social, material, physical, and mental resources to attain school achievement. But they are often lacking, especially for immigrant students. In an early adolescence context, this study assessed risk for school difficulties among European and non-European immigrants and the roles of socioeconomic characteristics, physical health, psychological health, social relationships, living environment, and unhealthy behaviours. Methods This cross-sectional study included 1,559 middle-school adolescents from north-eastern France, who completed a self-administered questionnaire including socioeconomic characteristics (gender, age, family structure, father’s occupation, and family income), WHO-Quality of life (measuring the four dimensions physical health, psychological health, social relationships, and living environment), unhealthy behaviours (last-30-day uses of tobacco, alcohol, cannabis, and other illicit drugs and no regular sports/physical activities), grade repetition, low school performance ( Results Grade repetition affected 14.8% of students, low school performance 8.2%, and school dropout ideation 3.9%. European immigrants had a higher risk for grade repetition only with a gender-age-adjusted odds ratio (OR) of 2.44, vs. French students. This odds ratio decreased to 1.76 (contribution 47%) with further adjustment for all confounders (family structure, father’s occupation, family income, physical health, psychological health, social relationships, living environment, and unhealthy behaviours). Non-European immigrants had a statistically higher risk for all grade repetition, low school performance, and school dropout ideation with ORs of 3.29, 3.02, and 3.42, respectively vs. French students. These odds ratios decreased to 1.76, 1.54, and 1.54, respectively (contributions 66%, 73%, and 78%) with further adjustment for all confounders. Conclusions Compared with French students, European immigrant students were more affected only by grade repetition while non-European immigrant students by all grade repetition, low school performance, and school dropout ideation. The contribution of socioeconomic characteristics, physical health, psychological health, social relationships, living environment, and unhealthy behaviours was very high and much higher for non-European than for European immigrant students. Public policy should focus on these factors and services to reduce school difficulties.

International audience