Evaluation of a Vibrotactile Device For Outdoor and Public Transport Pedestrian Navigation Using Virtual Reality

International audienceIt can be difficult to find your way in public transport, especially when the journey combines indoor and outdoor trans-portation. We designed an innovative vibrotactile device dedicated to guide a pedestrian in public transport. This multi-modal interface can be used to guide a pedestrian in unknown public transport. The device can be used by visually impaired person. The device has been tested during two main phases. The first step was to test the device using virtual reality while the second step test was to test the device in a real environment. This paper presents the first part of the evaluation of the device. We have developed a virtual reality scenario to assess the objective and subjective utility of the device. The results showed that the device could properly guide users. We also evaluated the usefulness of a warning vibration preceding a message. It was found that the vibration seems to introduce confusion to the pattern recognition by the user

Classification non supervisée d'un graphe de co-expression avec des méta-données pour la détection de micro-ARNs

National audienceNous présentons dans cet article une méthode de classification non supervisée de sommets d'un graphe qui est utilisée dans un contexte biologique particulier. La problématique est de détecter de manière non supervisée des micro-ARNs probables. Pour ce faire, nous utilisons une approche multi-noyaux permettant d'intégrer des informations sur le graphe de co-expression et des informations supplémentaires sur les sommets de ce graphe. Cette approche est rendue robuste par une technique de bagging de classifications. Les résultats obtenus donnent des groupes de miRNAs potentiels dont certains permettent de discriminer avec une bonne confiance les vrais miRNAs des faux positifs

Effect of aneurysm size on procedure-related rupture in patients with subarachnoid hemorrhage treated with coil occlusion

Objective: Procedure-related rupture is one of the most feared complications in treating patients with cerebral aneurysm. The primary aim of this study was to estimate the effect of aneurysm size on procedure-related rupture. We also estimated its effect on peri-procedural thromboembolic events. Methods: This observational study was conducted using routinely-collected health data on patients admitted for subarachnoid hemorrhage and treated with aneurysm coil occlusion in the CHU de Québec — Enfant-Jésus hospital from January 1st, 2000 until sample size was reached. Patients were identified from the Discharge Abstract Database using the Canadian Classification of Health codes. Assessment of complications was blind to aneurysm size. Logistic regression models were performed to test associations between aneurysm size and procedure-related rupture or peri-procedural thromboembolic events, and between both procedure-related rupture and thromboembolic events and patients' outcomes. Results: This study included 532 aneurysms treated with coil occlusion in 505 patients. Procedure-related rupture occurred in 34 patients (6.7%) and thromboembolic events in 53 (10.5%) patients. Aneurysms of 2 to 3 mm inclusively were not more significantly associated with procedure-related rupture or thromboembolic events than those larger than 3 mm (OR 1.02, 95% CI: 0.9–1.16, p = 0.78 and OR 1.06, 95% CI: 0.96–1.17, p = 0.3, respectively). However, procedure-related rupture had a significant effect on patient mortality (OR 3.86, 95% CI: 1.42–10.53, p < 0.01). Conclusions: Very small aneurysm size should not preclude aneurysm coil occlusion. Every measure should be taken to prevent procedure-related rupture as it is strongly associated with higher mortality

Comparison of Drosophila melanogaster Embryo and Adult Proteome by SWATH-MS Reveals Differential Regulation of Protein Synthesis, Degradation Machinery, and Metabolism Modules.

An important area of modern biology consists of understanding the relationship between genotype and phenotype. However, to understand this relationship it is essential to investigate one of the principal links between them: the proteome. With the development of recent mass-spectrometry approaches, it is now possible to quantify entire proteomes and thus relate them to different phenotypes. Here, we present a comparison of the proteome of two extreme developmental states in the well-established model organism Drosophila melanogaster: adult and embryo. Protein modules such as ribosome, proteasome, tricarboxylic acid cycle, glycolysis, or oxidative phosphorylation were found differentially expressed between the two developmental stages. Analysis of post-translation modifications of the proteins identified in this study indicates that they generally follow the same trend as their corresponding protein. Comparison between changes in the proteome and the transcriptome highlighted patterns of post-transcriptional regulation for the subunits of protein complexes such as the ribosome and the proteasome, whereas protein from modules such as TCA cycle, glycolysis, and oxidative phosphorylation seem to be coregulated at the transcriptional level. Finally, the impact of the endosymbiont Wolbachia pipientis on the proteome of both developmental states was also investigated.BBSR

Dual Suppression of the Cyclin-Dependent Kinase Inhibitors CDKN2C and CDKN1A in Human Melanoma

Resistance to BRAFV600E inhibitors is associated with reactivation of mitogen-activated protein kinase (MAPK) signaling at different levels in melanoma. To identify downstream effectors of MAPK signaling that could be used as potential additional therapeutic targets for BRAFV600E inhibitors, we used hTERT/CDK4R24C/p53DD-immortalized primary human melanocytes genetically modified to ectopically express BRAF V600E or NRAS G12D and observed induction of the AP-1 transcription factor family member c-Jun. Using a dominant negative approach, in vitro cell proliferation assays, western blots, and flow cytometry showed that MAPK signaling via BRAFV600E promotes melanoma cell proliferation at G1 through AP-1-mediated negative regulation of the INK4 family member, cyclin-dependent kinase inhibitor 2C (CDKN2C), and the CIP/KIP family member, cyclin-dependent kinase inhibitor 1A (CDKN1A). These effects were antagonized by pharmacological inhibition of CDKN2C and CDKN1A targets CDK2 and CDK4 in vitro. In contrast to BRAF V600E or NRAS G12D-expressing melanocytes, melanoma cells have an inherent resistance to suppression of AP-1 activity by BRAFV600E- or MEK-inhibitors. Here, CDK2/4 inhibition statistically significantly augmented the effects of BRAFV600E- or MEK-inhibitors on melanoma cell viability in vitro and growth in athymic nude Foxn1 nu mice (P = .03 when mean tumor volume at day 13 was compared for BRAFV600E inhibitor vs BRAFV600E inhibitor plus CDK2/4 inhibition; P = .02 when mean tumor volume was compared for MEK inhibitor vs MEK inhibitor plus CDK2/4 inhibition; P values were calculated by a two-sided Welch t test; n = 4–8 mice per group)

Efficacité de biofilms de bactéries As-oxydantes pour l'étape de traitement biologique d'eaux potabilisables arséniées

L'arsenic est un métalloïde toxique dont la présence, relativement fréquente, dans les eaux et les sols est liée soit au fond géochimique, soit aux activités humaines. En ce qui concerne les eaux destinées à la consommation, la législation impose une concentration maximale en arsenic de 10 µg.L-1. Les effets nocifs de l'arsenic sur la santé humaine rendent nécessaire le développement de technologies efficaces et peu couteuse pour éliminer cet élément des eaux potables, ainsi que dans les aquifères pollués et dans les effluents miniers (Wang et Zhao, 2009). Une unité de traitement biologique d'eaux potabilisable faiblement arséniée (As< 50µg/L), couplée à une unité de piégeage de l'As en sortie du bioréacteur, a été mise en œuvre sur un site réel afin d'étudier la robustesse du bioprocédé. Un bioréacteur contenant de la pouzzolane (matériau utilisé dans les traitements d'eaux) a été préalablement ensemencé par une souche bactérienne As(III) oxydante autotrophe (Thiomonas arsenivorans) (Battaglia-Brunet et al., 2002, Michon et al., 2010 ; Wan et al., 2010) puis alimenté par l'eau issue du forage à température ambiante (15-17°C) avec un fonctionnement discontinu (asservissement de l'alimentation du bioréacteur à la pompe du forage d'alimentation en eau). Le suivi du développement du biofilm As(III) oxydant au cours du traitement biologique a été réalisé par la recherche des gènes codant pour l'ARNr 16S (diversité bactérienne totale) et ceux codant pour une arsénite oxydase (aoxB) (diversité des bactéries As(III)-oxydantes). Ce suivi a montré une colonisation rapide et stable du support minéral par des bactéries endogènes de l'eau à traiter. Le rendement d'oxydation de l'étape d'oxydation biologique est compris entre 54 et 100 % avec des temps de séjour de 30 minutes à 7 minutes qui sont comparables à des temps de séjour de techniques classiques de traitement. Les concentrations résiduelles en As en sortie du procédé complet (oxydation biologique + piégeage) sont inférieures à 1 µg/L, et qui sont donc très encourageants pour une application industrielle

Hypovitaminosis D is associated with depression and anxiety in schizophrenia: results from the national FACE-SZ cohort. Running title: hypovitaminosis D, depression and anxiety in schizophrenia

International audienceBackground. Guidelines have been edited for the treatment of schizophrenia (SZ) and bipola

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen