Development of auditory repetition effects with age : evidence from EEG time-frequency analysis

La présentation répétée d’un son inconnu conduit à des effets de répétition comprenant la suppression (‘repetition suppression’ ou RS) ou l’augmentation (‘repetition enhancement’ ou RE) de l’activité neuronale. Ces phénomènes reflètent des mécanismes cérébraux impliquant un apprentissage perceptuel. L’objectif de ce mémoire de maitrise était d’apporter une perspective développementale de l’activité cérébrale sous-tendant l’apprentissage perceptuel auditif. L’EEG a été enregistré chez 101 participants sains âgés de 3 à 40 ans pendant un paradigme auditif passif durant lequel 30 pseudo-mots étaient répétés 6 fois chacun. Des analyses en temps- fréquence ont été calculées pour chaque répétition. La puissance spectrale enregistrées en EEG entre chaque répétition a été comparée au moyen de modèles linéaires mixtes. Les résultats montrent qu’un effet de répétition survient au cours du développement mais varie en fonction de l’âge et des bandes de fréquences. Du RS et RE ont été observés à tous les âges dans le thêta bas et le gamma respectivement. Un effet développemental a été trouvé de façon plus précoce pour le RS dans le thêta haut et de façon tardive pour le RE dans le thêta bas. Ces résultats montrent que les processus impliquant un apprentissage perceptif auditif, tel que le RS et le RE, suivent une trajectoire développementale spécifique en fonction des rythmes cérébraux. Les effets de répétition reflèteraient différents niveaux de traitement des stimuli qui se développeraient de manière indépendante. Des recherches supplémentaires seront nécessaires pour préciser le rôle fonctionnel des effets de répétitions sur le développement cognitif.The repeated presentation of unfamiliar sounds leads to repetition effects comprising repetition suppression (RS) and enhancement (RE) of neural activity. These phenomena reflect mechanisms involved in perceptual learning and are associated with a decrease or increase in EEG spectral powers. The objective of this Master’s thesis is to provide a developmental perspective of the cortical activity underlying auditory perceptual learning. EEG was recorded in 101 healthy participants ranging from 3 to 40 years during an auditory paradigm comprising 30 pseudowords repeated six times each. EEG time-frequency spectral power was calculated for each presentation and was compared to quantify repetition effects. Linear mixed model analysis revealed that some repetition effects occurred across ages and others varied with age in specific frequency bands. More precisely, RS and RE were found across ages in lower theta and gamma frequency bands respectively between the first and all subsequent pseudoword presentations. Developmental effects were seen in the RS observed in the higher theta/low alpha band and in the later occurring RE in the lower theta band. These results show that processes involved in auditory perceptual learning, such as RS and RE, are modulated by maturation. Further, repetition effects reflect different levels of stimulus processing and these levels seem to develop independently. More research is required to identify the exact functional roles of auditory repetitions effects on cognitive development

Suppression by thimerosal of ex-vivo CD4+ T cell response to influenza vaccine and induction of apoptosis in primary memory T cells.

International audienceThimerosal is a preservative used widely in vaccine formulations to prevent bacterial and fungal contamination in multidose vials of vaccine. Thimerosal was included in the multidose non-adjuvanted pandemic 2009 H1N1 vaccine Panenza. In the context of the analysis of the ex-vivo T cell responses directed against influenza vaccine, we discovered the in vitro toxicity Panenza, due to its content in thimerosal. Because thimerosal may skew the immune response to vaccines, we investigated in detail the ex-vivo effects of thimerosal on the fate and functions of T cells in response to TCR ligation. We report that ex-vivo exposure of quiescent or TCR-activated primary human T cells to thimerosal induced a dose-dependent apoptotic cell death associated with depolarization of mitochondrial membrane, generation of reactive oxygen species, cytochrome c release from the mitochondria and caspase-3 activation. Moreover, exposure to non-toxic concentrations of thimerosal induced cell cycle arrest in G0/G1 phase of TCR-activated T cells, and inhibition of the release of proinflammatory cytokines such as IFN gamma, IL-1 beta, TNF alpha, IL-2, as well as the chemokine MCP1. No shift towards Th2 or Th17 cells was detected. Overall these results underline the proapoptotic effect of thimerosal on primary human lymphocytes at concentrations 100 times less to those contained in the multidose vaccine, and they reveal the inhibitory effect of this preservative on T-cell proliferation and functions at nanomolar concentrations

The physiological burden of the 6-minute walk test compared with cardiopulmonary exercise stress test in patients with severe aortic atenosis

Background Management of aortic stenosis (AS) relies on symptoms. Exercise testing is recommended for asymptomatic patients with significant AS but is often experienced as forbidding and/or technically unrealistic for patients who are often frail, deconditioned, and intimidated by the exercise test. We compared the physiological burden assessed with gas exchange assessments to gauge and respiratory exchange ratio (RER) of a 6-minute walk test (6MWT) to a cardiopulmonary exercise stress test (CPET) in patients with severe AS. peak oxygen utilization Methods Adults with equivocal symptoms and severe AS (1-aortic valve area [AVA] ≤ 1.0 cm2 or AVA index ≤ 0.6 cm2/m2, 2-peak aortic jet velocity ≥ 4.0 m/sec, 3-mean transvalvular pressure gradient ≥ 40 mm Hg by rest or dobutamine stress echocardiography, or 4-aortic valve calcification ≥ 1200 in women or ≥ 2000 AU in men) were studied. All participants completed both a 6MWT and symptom-limited progressive bicycle exercise testing. Breath-by-breath gas analysis and 12-lead electrocardiography were completed during 6MWT and CPET. Results: Eleven patients were studied. Patients walked on average 330 ± 75 m during the 6MWT and achieved a maximal workload of 48 ± 14 watts during the CPET. During the 6MWT, peak maximal oxygen uptake (O2peak) was 12.8 ± 2.5 vs 10.8 ± 4.2 mL/kg/min during the CPET. Respiratory exchange ratio exceeded 1.1 in both the 6MWT and CPET indicating similarly high exertion. Compared with the CPET, a larger proportion of the 6MWT was performed at a high intensity level (78% ± 28% vs 33% ± 24% at > 85% V̇O2peak; P = 0.004). Conclusions The 6MWT with breath-by-breath gas analysis was well tolerated and able to achieve a physiological intense RER and O2peak that are similar to symptom-limited CPET in patients with severe AS.Introduction La prise en charge de la sténose aortique (SA) dépend des symptômes. L’épreuve d’effort est recommandée aux patients asymptomatiques qui ont une SA significative, mais elle est souvent perçue comme dangereuse et/ou théoriquement irréaliste chez ces patients qui sont souvent fragiles, en mauvaise forme et craintifs par l’épreuve d’effort. Nous avons comparé le fardeau physiologique calculé par la consommation maximale de l’oxygène (O2max) et le quotient respiratoire (QR) d’un test de marche de 6 minutes (TM6) et d'une épreuve d’effort maximal chez des patients avec une SA sévère. Méthodes Tous les patients présentaient une SA symptomatique et sévère (1-aire valvulaire aortique [AVA] ≤ 1,0 cm2 ouAVA ≤ 0,6 cm2/m2, 2-une vélocité maximale du flux aortique ≥ 4,0 m/sec, 3-un gradient de pression transvalvulaire moyen ≥ 40 mmHg au repos ou à l’échocardiographie à l’effort sous dobutamine ou 4-une calcification valvulaire aortique (AU) ≥ 1200 chez les femmes ou ≥ 2000 AU chez les hommes). Les participants ont effectué un TM6 et une ’épreuve d’effort maximal de type rampe sur vélo. L’analyse des échanges gazeux respiration par respiration et un électrocardiogramme à 12 dérivations ont été effectués durant le TM6 et l'épreuve d'effort maximal. Résultats Un total de 11 patients ont participé à l'étude. Les patients ont marché en moyenne 330 ± 75 m durant le TM6 et ont atteint une charge de travail maximale de 48 ± 14 watts durant l’épreuve d'effort maximal. Durant le TM6, le O2max était de 12,8 ± 2,5 vs 10,8 ± 4,2 ml/kg/min durant l’épreuve d'effort maximal. Le QR était supérieur à 1,1 au TM6 ainsi qu'à l’épreuve d'effort maximal. Comparativement à l’épreuve d'effort maximal, un pourcentage plus important au TM6 a été réalisée à une intensité élevée (78 % ± 28 % vs 33 % ± 24 % à > 85 % V̇O2max; P = 0,004). Conclusions Le TM6 avec mesure directe des échanges gazeux était bien toléré et susceptible d’atteindre des valeurs physiologiques d'intensité élevée pour le QR et le O2max. Les valeurs atteintes au TM6 étaient semblables à celles de l'épreuve d'effort maximal chez les patients avec une SA sévère

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Coproduction of biofuels and biochar by slow pyrolysis in a rotary kiln

Biochar has been heralded as a promising technology for climate change mitigation that can also benefit soils. Biochar is a carbonaceous solid produced by pyrolysis of biomass – the thermal decomposition of plant and plant-derived matter in the absence of oxygen. When added to soils, biochar has the potential to increase crop yields and suppress soil emissions of greenhouse gases, whilst sequestering carbon in a stable form. In addition to biochar, biomass pyrolysis produces liquids and gases that can serve as biofuels. Biochar production systems that generate excess heat or power are particularly environmentally and economically attractive. Rotary kilns are the favoured process reactor in many industries, given their potential to handle a wide range of feedstocks and provide good process control. This thesis investigates the potential to coproduce biochar and excess biofuels by slow pyrolysis in a pilot-scale rotary kiln. The work attempts to progress towards the ultimate aim of scaling up the rotary kiln and optimising its operating conditions to produce biochar of good quality along with an excess of useful biofuels. Experimental work, involving the development and application of new methodologies, was used to gain a better understanding of the process. The data gathered were then used to support preliminary numerical simulation efforts towards the development of a comprehensive process model. Five biomass feedstocks were considered: softwood pellets, miscanthus straw pellets, wheat straw pellets, oilseed rape straw pellets and raw rice husks. The granular flow of biomass feedstocks was observed in a short closed drum faced with acrylic and resting on rollers. All pelletized feedstocks displayed similar angles of repose, validating the use of softwood pellets as a model biomass for these feedstocks. Bed mixing, which can improve product uniformity, was slow under typical operating conditions, requiring 5 min to complete at 4 rpm for softwood pellets. Mixing quickened considerably at higher rotation rates. A digital image analysis method was developed to measure the distribution of solid residence times inside the rotary kiln. The mean residence time of softwood pellets ranged from 19 to 37 min under typical operating conditions, decreasing with increases in kiln rotation rate, but mostly unaffected by feeding rates. These findings show that kiln rotation rates must be selected to balance the residence time of solids inside the kiln with bed mixing levels. Thermogravimetry and differential scanning calorimetry were performed on samples of ground softwood pellets under five different heating profiles to study the kinetics and heat flows of the pyrolysis process. Both exothermic and endothermic regions were identified, with most reactions taking place between 250°C and 500°C. Results suggest that exothermic pyrolysis reactions can be promoted by altering the process heating rate, thereby improving net biofuel yield from the process. The thermogravimetric data collected was used to develop a distributed activation energy model (DAEM) of the kinetics of softwood pellet pyrolysis for integration into a comprehensive model of the process. The applicability of the kinetic model to large-scale processes was confirmed using a simplified process model developed to simulate biomass pyrolysis inside the pilot-scale rotary kiln. Although crude, the simplified process model produced sufficiently accurate estimates of char yield for preliminary design purposes. The simplified model also allowed important process parameters, such as kiln filling degree, solid residence time and heating rate, to be evaluated. A series of pyrolysis experiments was performed on the pilot-scale rotary kiln to evaluate the yields of biochar and biofuels and determine the temperature profile inside the kiln. This work required the design of a suspended thermocouple system that measures temperatures along the kiln, both in the gas phase and inside the solid bed. For most experiments at 550°C, a region of high temperature gas and solids was observed, possibly indicative of exothermic reactions. Biochar yield varied from 18% to 73% over the range of feedstocks and operating conditions tested. A vapour sampling methodology that relies on the use of a tracer gas was developed to determine the yield of pyrolysis liquids and gases. Due to analytical difficulties, it was not possible to obtain accurate mass closure with this method. However, the methodology revealed significant air ingress into the pilot-scale rotary kiln that is responsible for partially combusting biofuels produced by the process, thereby reducing their calorific value. Energy balances on the kiln confirmed that the calorific content of pyrolysis liquids and gases exceeds the energetic demand of the process, yielding between 0.3 and 11 MJ in excess biofuels per kg of biomass feedstock. An attempt was made to develop a multiphase model of the flow of vapours and solids inside the rotary kiln using computational fluid dynamics (CFD), but the continuous modelling approach was found inadequate to simulate the dense bed of biomass inside the kiln. The discrete element method (DEM) was sought as an alternative to model the granular flow of biomass inside the kiln. Extensive parameter calibration was required to reproduce the experimental behaviour of softwood pellets observed in the short closed drum. A model of the pilot-scale rotary kiln was constructed to simulate particle residence times. Further parameter calibration was required to replicate softwood pellet holdup inside the kiln. The calibrated model was able to reproduce the mean residence time of softwood pellets within 10% under different kiln operating conditions. However, simulated residence time distributions could not be established as a result of the long execution times required for this modelling work. Few data are currently available on large-scale continuous biomass pyrolysis processes; the experimental data gathered in this thesis help to fill this gap. Along with the numerical simulation work presented herein, they provide the foundation for the development of a comprehensive model of biomass pyrolysis in rotary kilns. Such a numerical model would prove invaluable in scaling up the process and maximizing its efficiency. Future work should consider the agronomic value and carbon sequestration potential of biochar produced under different operating conditions. In addition, the performance and efficiency of different conversion technologies for generating heat and power from biofuels need to be investigated

Cancers de l'enfant (données épidémiologiques, prise en charge thérapeutique actuelle et perspectives d'évolution)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

État des connaissances, perceptions et besoins professionnels de psychologues québécois face à la douance : une étude exploratoire

La présente étude descriptive à devis mixte, menée auprès de 224 psychologues québécois, examinait leur niveau de formation et de connaissances, leurs perceptions et leurs besoins professionnels au regard de la douance. Les résultats indiquent qu’une majorité de répondants a reçu de la formation en douance, mais avec un nombre d’heures de formation et des niveaux de connaissances faibles. Ils indiquent également une reconnaissance élevée des besoins particuliers des personnes douées. Des besoins de perfectionnement, de soutien et collaboration, et d’accès aux services pour la clientèle douée sont dégagés. La discussion soulève des pistes pour soutenir le travail des psychologues auprès d’une clientèle douée.This descriptive study, conducted among 224 psychologists in the province of Quebec using a mixed research approach, aimed to examine participants’ level of knowledge and training as well as attitudes and professional needs regarding giftedness. Results show that a majority of participants has received some training about giftedness, but with a low number of hours of training and low levels of knowledge. They also reveal a high level of recognition of the special needs of gifted people. Three categories of professional needs were identified: professional training, professional support and collaboration, and public services for the gifted. Emerging leads to support psychologists’ work with gifted people are discussed