Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14 gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300 range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14 RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14 represents one of the most common genetic causes of LOCA uncovered to date.

We study the influence of a membrane filter's internal pore structure on its flow and adsorptive fouling behaviour. Membrane performance is measured via (1) comparison between volumetric flow rate and throughput during filtration and (2) control of concentration of foulants at membrane pore outlets. Taking both measures into account, we address the merits and drawbacks of selected membrane pore structures. We first model layered planar membrane structures with intra-layer pore connections, and present comparisons between non-connected and connected structures. Our model predicts that membrane filters with connected pore structures lead to higher total volumetric throughput than those with non-connected structures, over the filter lifetime. We also provide a sufficient criterion for the concentration of particles escaping the filter to achieve a maximum in time (indicative of a membrane filter whose particle retention capability can deteriorate). Additionally, we find that the influence of intra-layer heterogeneity in pore-size distribution on filter performance depends on the connectivity properties of the pores.

Cognitive impairment is central to many psychiatric conditions and is a determinant factor of functioning. The evaluation of cognition is time-consuming and recourse to it limited by cost, accessibility of expertise, and, in the case of computerized batteries, equipment. The SCIP is a 15 minute paper and pencil evaluation of cognitive function which can be integrated into clinical practice. It is thus a tool which can assist in determining which patients require a more extensive evaluation and can inform the elaboration of a personalized treatment plan. Our group (Groupe Comorbidité psychiatrique et Dimensions) has validated a french translation of the SCIP and is testing the acceptability of its integration into clinical practice in selected clinical populations. We will present preliminary data regarding the use of the SCIP in adult attention deficit disorder. Forty adult patients with attention deficit disorder were invited to participate in the study. In order to maintain a sample representative of clinical practice the only exclusion criteria were inability to speak french and inability to give informed consent. Demographic characteristics were collected, and a multiaxial DSM-IV diagnosis determined by the treating physician, SCIP was administered. The time to administer the SCIP was recorded, and a qualitative questionnaire of patient impressions was completed. We will present preliminary results of this study.

Background: Mutations in the gene encoding Ubiquilin-2 (UBQLN2) are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). UBQLN2 plays a central role in ubiquitin proteasome system (UPS) and UBQLN2 up-regulation exacerbates TDP-43 cytoplasmic aggregates. Methods: To analyse interaction between UBQLN2 and TDP-43 and to produce a relevant ALS animal model, we have generated a new transgenic mouse expressing UBQLN2P497H under the neurofilament heavy (NFH) gene promoter. The mice were then bred with our previously described TDP-43G348C mice to generate double transgenic mice. Results: With low expression UBQLN2, the double transgenic mice developed TDP-43 cytosolic accumulations in motor neurons starting at 5 months of age. These double transgenic mice exhibited motor neuron loss, muscle atrophy, as well as motor and cognitive deficits during aging. The microglia from double transgenic mice were hyperresponsive to lipopolysaccharide (LPS). In vivo and in vitro analyses suggested that extra UBQLN2 proteins can exacerbate cytoplasmic TDP-43 accumulations by competing with the UPS for binding to ubiquitin. Thus, increasing the pool of ubiquitin promoted the UPS function with ensuing reduction of TDP-43 aggregation. Conclusions: In conclusion, the double transgenic UBQLN2P497H; TDP-43G348C mice provides a unique mouse model of ALS/FTD with enhanced TDP-43 pathology that can be exploited for drug testing.

Introduction: In the province of Québec, roughly 20% of the population lives in rural areas. Rural emergency departments (EDs) face different challenges than their urban counterparts. Yet, few studies have sought to understand these challenges. This study aims to survey Québec’s emergency physicians to: 1) identify problems specific to rural EDs, 2) find solutions for improving accessibility and quality of care offered in rural regions and, 3) rank solutions in order of priority. These results will allow data triangulation with other of our studies that seek to identify challenges faced by rural EDs and potential solutions. Methods: During the 2016 annual conference of the Québec Emergency Physicians’ Association, we asked physicians and residents (including those from urban EDs), to complete a survey about the challenges faced by rural EDs. The survey contained two sections. The first took the form of open-ended questions in which respondents could write three challenges about accessibility and quality of care in rural EDs (objective 1) and three solutions to address these challenges (objective 2). The second section listed 11 potential solutions identified in our previous study. The solutions were ranked based on their priority level on a five-point Likert scale that ranged from “not a priority” to “an absolute priority” (objective 3). We added the total number of points for each solution and produced a ranking list. Results: Ninety-one physicians out of the 417 at the conference completed the survey; 58% came from urban EDs and 42% from rural EDs. Open-ended questions suggest that access to specialists and interfacility transfers are the principal challenges faced by rural EDs. The top five solutions identified as the highest priorities were: 1) care protocols, 2) improvement of interfacility transfers, 3) training with simulators, 4) targeted ultrasound and, 5) implementation of staff retention and recruitment strategies. Conclusion: This study is relevant and useful as roughly a quarter of attendants at the conference spontaneously volunteered to help identify and prioritize solutions to foster the accessibility and quality of care in rural EDs. Furthermore, it represents a stepping stone for our recently-launched wide-scope study, Urgences Rurales 360, that aims to explore problems faced by every of the 28 rural EDs in Québec and the solutions that could be implemented to resolve them.

Objectives: Relatively few studies have investigated relationships between performance on clinical memory measures and indexes of underlying neuropathology related to Alzheimer’s disease (AD). This study investigated predictive relationships between Free and Cued Selective Reminding Test (FCSRT) cue efficiency (CE) and free-recall (FR) measures and brain amyloid levels, hippocampal volume (HV), and regional cortical thickness. Methods: Thirty-one older controls without memory complaints and 60 patients presenting memory complaints underwent the FCSRT, amyloid imaging using [F18]-flutemetamol positron emission tomography, and surface-based morphometry (SBM) using brain magnetic resonance imaging. Three groups were considered: patients with high (Aβ+P) and low (Aβ− P) amyloid load and controls with low amyloid load (Aβ− C). Results: Aβ+P showed lower CE than both Aβ− groups, but the Aβ− groups did not differ significantly. In contrast, FR discriminated all groups. SBM analyses revealed that CE indexes were correlated with the cortical thickness of a wider set of left-lateralized temporal and parietal regions than FR. Regression analyses demonstrated that amyloid load and left HV independently predicted FCSRT scores. Moreover, CE indexes were predicted by the cortical thickness of some regions involved in early AD, such as the entorhinal cortex. Conclusions: Compared to FR measures, CE indexes appear to be more specific for differentiating persons on the basis of amyloid load. Both CE and FR performance were predicted independently by brain amyloid load and reduced left HV. However, CE performance was also predicted by the cortical thickness of regions known to be atrophic early in AD. (JINS, 2016, 22, 991–1004)

Background: It has been hypothesized that [18F]-sodium fluoride (NaF) uptake imaged with positron emission tomography (PET) binds to hydroxyapatite molecules expressed in regions with active calcification. Therefore, we aimed to validate NaF as a marker of hydroxyapatite expression in high-risk carotid plaque. Methods: Eleven patients (69 ± 5 years, 3 female) scheduled for carotid endarterectomy were prospectively recruited for NaF PET/CT. One patient received a second contralateral endarterectomy; two patients were excluded (intolerance to contrast media and PET/CT misalignment). The bifurcation of the common carotid was used as the reference point; NaF uptake (tissue to blood ratio - TBR) was measured at every PET slice extending 2 cm above and below the bifurcation. Excised plaque was immunostained with Goldner’s Trichrome and whole-slide digitized images were used to quantify hydroxyapatite expression. Pathology was co-registered with PET. Results: NaF uptake was related to the extent of hydroxyapatite expression (r=0.45, p<0.001). Upon classifying bilateral plaque for symptomatology, symptomatic plaque was associated with cerebrovascular events (3.75±1.1 TBR, n=9) and had greater NaF uptake than clinically silent asymptomatic plaque (2.79±0.6 TBR, n=11) (p=0.04). Conclusion: NaF uptake is related to hydroxyapatite expression and is increased in plaque associated with cerebrovascular events. NaF may serve as a novel biomarker of active calcification and plaque vulnerability.

The most common method of vibration control is the use of the dynamic absorbers. Two types of absorbers can be found: Linear and nonlinear. The use of linear absorbers allows reducing vibration but only at the resonance frequency, whereas nonlinear absorbers attenuate vibration on a wide band of frequency. In this paper, a nonlinear two degrees of freedom (DOF) model is developed. A cubic nonlinearity induced by a gap is considered. The objective of the paper is to characterize nonlinear vibration of the system by applying explicit formulation (EF). An experimental study is performed to validate the numerical results. The jump phenomenon is the principal nonlinear dynamic phenomenon observed on both numerical and experimental investigations.

In this paper we present the design of a compact active cardiac stabilizer based onplanar compliant mechanisms and piezoelectric actuators. Considering an assembly of planarmanufactured structures helps to simplify the manufacturing process and may increase thecompactness. Parallel architectures constitute interesting solutions for their intrinsicstiffness properties, but in a planar configuration parallel manipulators often exhibitkinematic singularities. Two design approaches for planar parallel compliant mechanismsare presented in this paper. One design approach consists in designing a passive compliantmechanism in a configuration close to the singularity by introducing some asymmetriesduring the manufacturing process. The second design approach consists in taking advantageof the singularities of parallel manipulators to obtain non-trivial solutions. The newproposed active stabilizer, composed of planar compliant mechanisms, is introduced and itsperformances are discussed.

Afin d’évaluer les conséquences des rejets radioactifs provenant des réacteursaccidentés de la centrale nucléaire de Fukushima-Daichi sur l’environnement terrestrefrançais, l’IRSN a renforcé son plan de surveillance en échantillonnant notamment de lavégétation de prairie, du lait et de la viande des troupeaux en pâture entre avril etnovembre 2011. Ces prélèvements et ces mesures ont, entre autres, permis d’évaluer dansdes conditions de dépôts réels la chronologie des transferts du césium-134 de l’herbe aulait et à la viande. Les premières mesures significatives en 134Cs apparaissentdans l’herbe et dans le lait cinq à sept jours après la première mesure significative dansl’air. Les activités maximales atteignent 0,4 Bq.kg–1 d’herbe fraiche et0,028 Bq.L–1 dans le lait. Dans la viande, les premières mesuressignificatives apparaissent mi-avril avec une activité maximale mesurée de 0,036Bq.kg–1, avec de fortes variations d’une espèce animale à une autre. Lescoefficients de transfert moyens calculés sont proches de ceux disponibles dans lalittérature avec 0,22 j.kg–1 pour la viande de mouton, et de 0,09 et0,0014 j.L–1 pour le lait de chèvre et de vache, respectivement.

Acanthocephaloides geneticus sp.nov. is described from Arnoglossus laterna (Bothidae) from the Mediterranean littoral (Sète-France). The new species most closely resembles Acanthocephaloides propinquus (Dujardin, 1845) Meyer, 1932, whose type host is Gobius niger (Gobiidae). A genetic comparison of the parasites collected from these two Teleostean fishes has confirmed the value of morphological differences which seemed too slight to raise the populations to species status.

In the eastern Mediterranean, the copepod Lepeophtheirus thompsoni Baird, 1850, has been reported to infest turbot, brill and flounder. By combining several methods, including enzyme electrophoresis, we show that this species is found only in turbot. By contrast, brill and flounder are infested by a species of Lepeophtheirus that corresponds to no other species reported in the literature. We propose that the species be designated as L. europaensis and we describe the characteristics of the gravid female. This study was extended to the Atlantic populations of flatfishes and includes an investigation of L. pectoralis (Muller, 1776), which infects flounder in the North Sea; we also confirmed the presence of L. thompsoni (Baird, 1850) over the whole geographic range of turbot. Lastly, we discuss the specificity and distribution of these species along the European coasts.

Nançay radio astronomy station teams are involved in several aspects of the Research and Development (R&D) for radio astronomy detectors and systems: i) Microelectronics: Low Noise Amplifiers (LNA), receiver on chip and system in package. The long-term goal is to provide sub-systems for the future Square Kilometer Array and its Pathfinders. A beamformer chip has been integrated in the FP6 SKADS dense aperture array technology demonstrator EMBRACE. Wide band SiGe LNAs are developed, beamformers with in-chip control are studied and more complex integrated receivers are designed for the european Aperture Array Verification Programme demonstrator. ii) Digital signal processing: EMBRACE beamforming has been implementedin the digital backend and RFI-mitigation oriented signal processing has been designed for realtime systems,including work for FP6 SKADS and FP7 PrepSKA. iii) A study of Phased Array Feeds has started in 2008, in order to study the radio electric properties of PAFs at the focus of large F/D telescopes, such as the Nançay Radio Telescope, as well as to test PAFsystems in collaboration with the SPP/IRFU and LAL/IN2P3 laboratories.

Airborne 137Cs level in France is not decreasing significantly anymore (mean yearly value around 0,25 µ Bq.m-3 contrarily to what was noticed in the past decades. This observation points out the role of processes that delay the atmospheric cleaning and participate to the persistence of radionuclide in the air at ground-level after a deposit, in the frame of medium as well as long-dated post-accidental contexts. The current background level also yields to consider 137Cs in the atmosphere as a tracer of atmospheric processes like resuspension and re-emission from biomass burnings. This allows us to explain 2/3 of the peaks observed over the last six years. The remaining 1/3 is mainly noticed in winter when spreading of pollutants in the atmosphere is often weak due to temperature gradient inversion. On average, continental air masses are responsible for increases by a factor of 3 while oceanic air masses are characterised by levels 3 times lower, compared to the mean value. Feeding of 137Cs in air at ground-level is the result of both local resuspension that signs 137Cs activity levels in soils to which is added a remote contribution from time to time (resuspension of Saharan dust or re-emission from fires occurring in eastern territories with high 137Cs deposition level). Finally, 137Cs activity levels in air masses crossing over France can be described on average by a longitudinal gradient.

This paper is devoted to the exact resolution of a strongly NP-hard resource-constrained scheduling problem, the Process Move Programming problem, which arises in relation to the operability of certain high-availability real-time distributed systems. Based on the study of the polytope defined as the convex hull of the incidence vectors of the admissible process move programs, we present a branch-and-cut algorithm along with extensive computational results demonstrating its practical relevance, in terms of both exact and approximate resolution when the instance size increases.