Detection of alpha-synuclein conformational variants from gastro-intestinal biopsy tissue as a potential biomarker for Parkinson's disease

Aims Gastrointestinal (GI) a-synuclein (aSyn) detection as a potential biomarker of Parkinson’s disease (PD) is challenged by conflicting results of recent studies. To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in GI biopsies obtained from a longitudinal, clinically wellcharacterized cohort of PD patients and healthy controls (HC). Methods With immunohistochemistry (IHC), we used antibodies reactive for total, phosphorylated and oligomeric aSyn; with aSyn proximity ligation assay (AS-PLA), we targeted oligomeric aSyn species specifically; and with paraffin-embedded tissue blot (AS-PET-blot) we aimed to detect fibrillary, synaptic aSyn. Results A total of 163 tissue blocks were collected from 51 PD patients (113 blocks) and 21 HC (50 blocks). In 31 PD patients, biopsies were taken before the PD diagnosis (Prodromal); while in 20 PD patients biopsies were obtained after diagnosis (Manifest). The majority of tissues blocks were from large intestine (62%), followed by small intestine (21%), stomach (10%) and oesophagus (7%). With IHC, four staining patterns were detected (neuritic, ganglionic, epithelial and cellular), while two distinct staining patterns were detected both with AS-PLA (cellular and diffuse signal) and with AS-PET-blot (aSyn-localized and pericrypt signal). The level of agreement between different techniques was low and no single technique or staining pattern reliably distinguished PD patients (Prodromal or Manifest) from HC. Conclusions Our study suggests that detection of aSyn conformational variants currently considered pathological is not adequate for the diagnosis or prediction of PD. Future studies utilizing novel ultrasensitive amyloid aggregation assays may increase sensitivity and specificity.</p

Vivre ensemble et séparés dans les quartiers nord-est de Paris (ethnologie d'un nouveau monde urbain)

Les quartiers du nord-est de Paris organisés autour des rues de faubourg et des anciens villages sont l objet depuis plusieurs années de processus de gentrification. Dans ce contexte a émergé un monde urbain au sens d un espace social cohérent aux yeux d un certain nombre d acteurs parmi lesquels les nouvelles classes moyennes et supérieures . L objectif de cette thèse qui relève d une anthropologie du familier est d analyser ce monde, c est-à-dire les manières spécifiques dont les acteurs s y comportent quand ils le pratiquent. L observation de diverses situations a permis de dégager trois logiques d action : la quête d un espace urbain singulier à nulle autre pareille ; la participation à des dispositifs favorisant le faire ensemble selon trois modalités, l acteur urbain, l ami et l habitant ; enfin, la pratique de l ethnologie généralisée. Ces manières d agir sont autant de façons d organiser les relations et les rapports sociaux et de vivre ainsi ensemble et séparés.The neighbourhoods of the north-east of Paris, organised around suburban streets and former villages, have for several years now been undergoing a process of gentrification. Within this context has emerged an urban world in the sense of a social space which is coherent in the eyes of certain people, amongst whom the new middle and upper social classes. The aim of this thesis in the anthropology of the familiar is to analyse this world, that is, the specific behaviour patterns of the players who enter it. The observation of diverse situations highlights three logical forms of behaviour: the search for a unique urban environment, different to any other; participation in devices which favour doing things together with interaction in three forms, the urban player, the friend and the inhabitant; and the practice of generalised ethnology. These forms of action constitute the different ways to organise social relations/relationships and consequently to live together and separately.PARIS-Médiathèque MQB (751132304) / SudocPARIS-Fondation MSH (751062301) / SudocSudocFranceF

Managing Planned Disruptions of Mass Transit Systems

TRB Transportation Research Board - 95th annual meeting, Jan 2016, Washington D. C., United StatesUnplanned disruptions of rail transit networks have been studied extensively. Planned disruptions for works essentially are different mainly because of their longer duration, which allows passengers to build alternative route choice strategies. The literature on this topic remains scarce. In this study, a novel methodology was proposed to enable operators to evaluate different disruption management schemes and to obtain explicit estimations of travel times, passenger comfort flows, and levels of service. Statistical tools were used to evaluate the different strategies. The methodology is illustrated here through a large-scale application to a real line disruption in Paris. The disruption took place in July 2015 as the result of network maintenance work and affected Line A of Réseau Express Régional, a major suburban railway line that provides more than 1 million trips on a typical working day. Study results indicated that the disruption would have significantly increased the generalized cost (GC) of passengers if no action had been taken. The operator's disruption management scheme included bus bridging and increases in service frequency on alternative routes. Evaluation showed that this plan restored the average GC across the whole network. Passengers who initially used the disrupted line experienced increased GC when they used the longer, alternative routes. Passengers who initially used those alternative routes experienced lower GC as a result of the increase in service frequency. Finally, capacity problems were observed on the buses that ensured a bridge across the disrupted link

Appropriation des notions de vulnérabilité et de résilience : enseignements de 3 territoires inondables

International audienceFrom about fifty conversations led with professionals and with inhabitants in three sites confronted with a problem of recurring flood, we examine if the words resilience and vulnerability appears spontaneously and which contents the interviewees give to them. The studied sites are the Val de Loire between the municipalities of Angers and Saumur, the peninsula of Ambès in Gironde and the valley of Argens in the Var. It seems the concept of resilience has to be introduced before could be spontaneously used. Using of the word vulnerability is easier. The concept of resilience seems too fuzzy or too complex to be of use to the local dialogue. Some use it all the same with the aim of carrying the idea that the territory and the society have to change. A sliding occurred between the initial concept and the way the local society read it.A partir d'une cinquantaine d'entretiens menés auprès de professionnels et d'habitants dans trois sites confrontés à une problématique d'inondation récurrente, nous examinons si les mots résilience et vulnérabilité apparaissent spontanément dans les témoignages et quel contenu les interviewés leur donnent. Les sites étudiés sont le val de Loire entre les communes d'Angers et de Saumur, la presqu'île d'Ambès en Gironde et la vallée de l'Argens dans le Var. Il apparaît que pour utiliser le concept de résilience spontanément, il faut avoir été initié. L’usage du terme vulnérabilité est plus courant. Le concept de résilience apparaît trop flou ou trop complexe pour servir au dialogue local. Certains l'utilisent quand même dans le but de porter l'idée que le territoire et la société doivent changer. Un glissement s’est produit entre le concept initial et la façon dont il est reçu localement