Human lung fibroblasts may modulate dendritic cell phenotype and function: results from a pilot in vitro study

International audienceAbstractIn human lung fibrotic lesions, fibroblasts were shown to be closely associated with immature dendritic cell (DC) accumulation. The aim of the present pilot study was to characterize the role of pulmonary fibroblasts on DC phenotype and function, using co-culture of lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and from control patients, with a DC cell line MUTZ-3. We observed that co-culture of lung control and IPF fibroblasts with DCs reduced the expression of specific DC markers and down-regulated their T-cell stimulatory activity. This suggests that pulmonary fibroblasts might sustain chronic inflammation in the fibrotic lung by maintaining in situ a pool of immature DCs

A role for dendritic cells in bleomycin-induced pulmonary fibrosis in mice?

RATIONALE: Lung dendritic cells (DCs) have been shown to accumulate in human fibrotic lung disease, but little is known concerning a role for DCs in the pathogenesis of fibrotic lung. OBJECTIVES: To characterize lung DCs in an in vivo model of bleomycin-induced pulmonary fibrosis in mice. METHODS: We characterized the kinetics and activation of pulmonary DCs during the course of bleomycin-induced lung injury by flow cytometry on lung single-cell suspensions. We also characterized the lymphocytes accumulating in bleomycin lung and the chemokines susceptible to favor the recruitment of immune cells. MEASUREMENTS AND MAIN RESULTS: We show, for the first time, that increased numbers of CD11c(+)/major histocompatibility complex class II(+) DCs, including CD11b(hi) monocyte-derived inflammatory DCs, infiltrate the lung of treated animals during the fibrotic phase of the response to bleomycin. These DCs are mature DCs expressing CD40, CD86, and CD83. They are associated with increased numbers of recently activated memory T cells expressing CD44, CD40L, and CD28, suggesting that fully mature DCs and Ag-experienced T cells can drive an efficient effector immune response within bleomycin lung. Most importantly, when DCs are inactivated with VAG539, a recently described new immunomodulator, VAG539 treatment attenuates the hallmarks of bleomycin lung injury. CONCLUSIONS: These findings identify lung DCs as key proinflammatory cells potentially able to sustain pulmonary inflammation and fibrosis in the bleomycin model

Transcutaneous electrical nerve stimulation for acute pain: A review

Background: This is a second update of a Cochrane Review originally published in Issue 2, 2009. Transcutaneous Electrical Nerve Stimulation (TENS) is a non-pharmacological agent, based on delivering low voltage electrical currents to the skin. TENS is used by people to treat a variety of pain conditions. Objectives: To assess the analgesic effectiveness of TENS, as a sole treatment, for acute pain in adults. Search methods: We searched the following databases up to 3 December 2014: the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; EMBASE; CINAHL; and AMED. We also checked the reference lists of included trials. Selection criteria: We included randomised controlled trials (RCTs) of adults with acute pain (< 12 weeks) if they examined TENS given as a sole treatment and assessed pain with subjective pain scales. Trials were eligible if they compared TENS to placebo TENS, no treatment controls, pharmacological interventions or non-pharmacological interventions. We excluded trials on experimental pain, case reports, clinical observations, letters, abstracts or reviews. Also we excluded trials investigating the effect of TENS on pain during childbirth (labour), primary dysmenorrhoea or dental procedures. Studies where TENS was given with another treatment as part of the formal trial design were excluded. We did not restrict any articles based on language of publication. Data collection and analysis Two review authors independently assessed study eligibility and carried out study selection, data extraction, 'Risk of bias' assessment and analyses of data. We extracted data on the following: types of participants and pain condition, trial design and methods, treatment parameters, adverse effects, and outcome measures. We contacted trial authors for additional information if necessary. Main results: We included 12 trials in the original review (2009) and included no further trials in the first update (2011). An additional seven new trials met the inclusion criteria in this second update. In total, we included 19 RCTs involving 1346 participants at entry, with 11 trials awaiting classification either because the full text was unavailable or information in the full text failed to clarify eligibility. We excluded most trials because TENS was given in combination with another treatment as part of the formal study design or TENS was not delivered using appropriate TENS technique. The types of acute pain included in this Cochrane Review were procedural pain, e.g. cervical laser treatment, venepuncture, screening flexible sigmoidoscopy and non-procedural pain, e.g. postpartum uterine contractions and rib fractures. We pooled data for pain intensity for six trials (seven comparisons) comparing TENS with placebo but the I2 statistic suggested substantial heterogeneity. Mean difference (MD) with 95% confidence intervals (CIs) on a visual analogue scale (VAS, 100 mm) was -24.62 mm (95% CI -31.79 to -17.46) in favour of TENS. Data for the proportion of participants achieving ≥ 50% reduction in pain was pooled for four trials (seven comparisons) and relative risk was 3.91 (95% CI 2.42 to 6.32) in favour of TENS over placebo. We pooled data for pain intensity from five trials (seven comparisons) but the I2 statistic suggested considerable heterogeneity. MD was -19.05 mm (95% CI -27.30 to -10.79) in favour of TENS using a random-effects model. It was not possible to pool other data. There was a high risk of bias associated with inadequate sample sizes in treatment arms and unsuccessful blinding of treatment interventions. Seven trials reported minor adverse effects, such as mild erythema and itching underneath the electrodes and participants disliking TENS sensation. Authors' conclusions: This Cochrane Review update includes seven new trials, in addition to the 12 trials reviewed in the first update in 2011. The analysis provides tentative evidence that TENS reduces pain intensity over and above that seen with placebo (no current) TENS when administered as a stand-alone treatment for acute pain in adults. The high risk of bias associated with inadequate sample sizes in treatment arms and unsuccessful blinding of treatment interventions makes definitive conclusions impossible. There was incomplete reporting of treatment in many reports making replication of trials impossible

The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

In healthy circumstances the immune system coordinates tissue repair responses in a tight balance that entails efficient inflammation for removal of potential threats, proper wound closure, and regeneration to regain tissue function. Pathological conditions, continuous exposure to noxious agents, and even ageing can dysregulate immune responses after injury. This dysregulation can lead to a chronic repair mechanism known as fibrosis. Alterations in wound healing can occur in many organs, but our focus lies with the lung as it requires highly regulated immune and repair responses with its continuous exposure to airborne threats. Dysregulated repair responses can lead to pulmonary fibrosis but the exact reason for its development is often not known. Here, we review the diversity of innate immune cells of myeloid origin that are involved in tissue repair and we illustrate how these cell types can contribute to the development of pulmonary fibrosis. Moreover, we briefly discuss the effect of age on innate immune responses and therefore on wound healing and we conclude with the implications of current knowledge on the avenues for future research

Methodology implementation for multiobjective optimisation for nuclear fleet evolution scenarios

La question de l’évolution du parc nucléaire français peut être considérée via l’étude de scénarios électronucléaires. Ces études présentent un rôle important, compte-tenu des enjeux, de l’ampleur des investissements, des durées et de la complexité des systèmes concernés, et fournissent des éléments d’aide au processus décisionnel. Elles sont menées à l’aide du code COSI (développé au CEA/DEN), qui permet de calculer les inventaires et les flux de matières transitant dans le cycle (réacteurs nucléaires et installations associées), via notamment le couplage avec le code d’évolution CESAR. Les études actuelles menées avec COSI nécessitent de définir les paramètres d’entrée des scénarios simulés, de sorte à satisfaire différents critères comme minimiser la consommation d’uranium naturel, la production de déchets, etc. Ces paramètres portent notamment sur les quantités et l’ordonnancement des combustibles usés au retraitement ou encore le nombre, la filière et les dates de mises en service des réacteurs à déployer. Le présent travail vise à développer, valider et appliquer une méthodologie d’optimisation couplée à COSI pour la recherche de scénarios électronucléaires optimaux pour un problème multicritère. Cette méthodologie repose en premier lieu sur la réduction de la durée d’évaluation d’un scénario afin de permettre l’utilisation de méthodes d’optimisation en un temps raisonnable. Dans ce cadre, des métamodèles d’irradiation par réseaux de neurones sont établis à l’aide de la plateforme URANIE (développée au CEA/DEN) et sont implémentés dans COSI. L’objet du travail est ensuite d’utiliser, adapter et comparer différentes méthodes d’optimisation, telles que l’algorithme génétique et l’essaim particulaire disponibles dans la plateforme URANIE, afin de définir une méthodologie adéquate pour ce sujet d’étude spécifique. La mise en place de cette méthodologie suit une approche incrémentale qui fait intervenir des ajouts successifs de critères, contraintes et variables de décision dans la définition du problème d’optimisation. Les variables ajoutées au problème, qui décrivent la cinétique de déploiement des réacteurs et la stratégie de retraitement des combustibles usés, sont choisies en fonction de leur sensibilité sur les critères définis. Cette approche permet de faciliter l’interprétation des scénarios optimaux, la détection d’éventuelles difficultés liées au processus d’optimisation, et finalement d’émettre des recommandations d’utilisation de la méthodologie mise en place en fonction de la nature du problème. Les études d'optimisation s’appuient sur un scénario de déploiement de réacteurs à neutrons rapides avec recyclage du plutonium, inspiré des études menées dans le cadre de la loi de 2006 sur la gestion des matières et déchets radioactifs. Une illustration des possibilités de la méthodologie est réalisée sur ce scénario, et permet notamment de démontrer le caractère optimal du scénario issu des études menées selon cette loi vis-à-vis de la limitation de l’entreposage de matières fissiles. Ce résultat souligne l’importance de la mise en œuvre d’une gestion dynamique du plutonium via le recours au combustible MOX pour le déploiement progressif des RNR.The issue of the evolution French nuclear fleet can be considered through the study of nuclear transition scenarios. These studies are of paramount importance as their results can greatly affect the decision making process, given that they take into account industrial concerns, investments, time, and nuclear system complexity. Such studies can be performed with the COSI code (developed at the CEA/DEN), which enables the calculation of matter inventories and fluxes across the fuel cycle (nuclear reactors and associated facilities), especially when coupled with the CESAR depletion code. The studies today performed with COSI require the definition of the various scenarios’ input parameters, in order to fulfil different objectives such as minimising natural uranium consumption, waste production and so on. These parameters concern the quantities and the scheduling of spent fuel destined for reprocessing, and the number, the type and the commissioning dates of deployed reactors.This work aims to develop, validate and apply an optimisation methodology coupled with COSI, in order to determine optimal nuclear transition scenarios for a multi-objective platform. Firstly, this methodology is based on the acceleration of scenario evaluation, enabling the use of optimisation methods in a reasonable time-frame. With this goal in mind, artificial neural network irradiation surrogate models are created with the URANIE platform (developed at the CEA/DEN) and are implemented within COSI. The next step in this work is to use, adapt and compare different optimisation methods, such as URANIE’s genetic algorithm and particle swarm methods, in order to define a methodology suited to this type of study. This methodology development is based on an incremental approach which progressively adds objectives, constraints and decision variables to the optimisation problem definition. The variables added, which are related to reactor deployment and spent fuel reprocessing strategies, are chosen according to their sensitivity to the defined objectives. This approach makes optimal scenarios interpretation easier, makes it possible to identify potential difficulties with the optimisation process, and then to provide recommendations on the use of the deployed methodology according to the problem type. The optimisation studies consider a fast reactor deployment scenario with plutonium recycling, which is inspired by studies carried out in the scope of the 2006 Act for Waste Management. An illustration of the possibilities of this methodology is provided with this scenario, demonstrating the optimality of the scenario inspired by the studies that were carried out for the 2006 Act, regarding stored fissile materials limitation. This result highlights the importance of dynamic plutonium management through MOX fuel usage during fast reactor deployment

La numération des érythroblastes circulants, étude comparative de 133 échantillons par trois méthodes (automate compte-globules, cytométrie en flux, microscopie optique)

PARIS-BIUP (751062107) / SudocSudocFranceF

Développement d'une méthodologie pour l'optimisation multicritère de scénarios d'évolution du parc nucléaire

The issue of the evolution French nuclear fleet can be considered through the study of nuclear transition scenarios. These studies are of paramount importance as their results can greatly affect the decision making process, given that they take into account industrial concerns, investments, time, and nuclear system complexity. Such studies can be performed with the COSI code (developed at the CEA/DEN), which enables the calculation of matter inventories and fluxes across the fuel cycle (nuclear reactors and associated facilities), especially when coupled with the CESAR depletion code. The studies today performed with COSI require the definition of the various scenarios’ input parameters, in order to fulfil different objectives such as minimising natural uranium consumption, waste production and so on. These parameters concern the quantities and the scheduling of spent fuel destined for reprocessing, and the number, the type and the commissioning dates of deployed reactors.This work aims to develop, validate and apply an optimisation methodology coupled with COSI, in order to determine optimal nuclear transition scenarios for a multi-objective platform. Firstly, this methodology is based on the acceleration of scenario evaluation, enabling the use of optimisation methods in a reasonable time-frame. With this goal in mind, artificial neural network irradiation surrogate models are created with the URANIE platform (developed at the CEA/DEN) and are implemented within COSI. The next step in this work is to use, adapt and compare different optimisation methods, such as URANIE’s genetic algorithm and particle swarm methods, in order to define a methodology suited to this type of study. This methodology development is based on an incremental approach which progressively adds objectives, constraints and decision variables to the optimisation problem definition. The variables added, which are related to reactor deployment and spent fuel reprocessing strategies, are chosen according to their sensitivity to the defined objectives. This approach makes optimal scenarios interpretation easier, makes it possible to identify potential difficulties with the optimisation process, and then to provide recommendations on the use of the deployed methodology according to the problem type. The optimisation studies consider a fast reactor deployment scenario with plutonium recycling, which is inspired by studies carried out in the scope of the 2006 Act for Waste Management. An illustration of the possibilities of this methodology is provided with this scenario, demonstrating the optimality of the scenario inspired by the studies that were carried out for the 2006 Act, regarding stored fissile materials limitation. This result highlights the importance of dynamic plutonium management through MOX fuel usage during fast reactor deployment.La question de l’évolution du parc nucléaire français peut être considérée via l’étude de scénarios électronucléaires. Ces études présentent un rôle important, compte-tenu des enjeux, de l’ampleur des investissements, des durées et de la complexité des systèmes concernés, et fournissent des éléments d’aide au processus décisionnel. Elles sont menées à l’aide du code COSI (développé au CEA/DEN), qui permet de calculer les inventaires et les flux de matières transitant dans le cycle (réacteurs nucléaires et installations associées), via notamment le couplage avec le code d’évolution CESAR. Les études actuelles menées avec COSI nécessitent de définir les paramètres d’entrée des scénarios simulés, de sorte à satisfaire différents critères comme minimiser la consommation d’uranium naturel, la production de déchets, etc. Ces paramètres portent notamment sur les quantités et l’ordonnancement des combustibles usés au retraitement ou encore le nombre, la filière et les dates de mises en service des réacteurs à déployer. Le présent travail vise à développer, valider et appliquer une méthodologie d’optimisation couplée à COSI pour la recherche de scénarios électronucléaires optimaux pour un problème multicritère. Cette méthodologie repose en premier lieu sur la réduction de la durée d’évaluation d’un scénario afin de permettre l’utilisation de méthodes d’optimisation en un temps raisonnable. Dans ce cadre, des métamodèles d’irradiation par réseaux de neurones sont établis à l’aide de la plateforme URANIE (développée au CEA/DEN) et sont implémentés dans COSI. L’objet du travail est ensuite d’utiliser, adapter et comparer différentes méthodes d’optimisation, telles que l’algorithme génétique et l’essaim particulaire disponibles dans la plateforme URANIE, afin de définir une méthodologie adéquate pour ce sujet d’étude spécifique. La mise en place de cette méthodologie suit une approche incrémentale qui fait intervenir des ajouts successifs de critères, contraintes et variables de décision dans la définition du problème d’optimisation. Les variables ajoutées au problème, qui décrivent la cinétique de déploiement des réacteurs et la stratégie de retraitement des combustibles usés, sont choisies en fonction de leur sensibilité sur les critères définis. Cette approche permet de faciliter l’interprétation des scénarios optimaux, la détection d’éventuelles difficultés liées au processus d’optimisation, et finalement d’émettre des recommandations d’utilisation de la méthodologie mise en place en fonction de la nature du problème. Les études d'optimisation s’appuient sur un scénario de déploiement de réacteurs à neutrons rapides avec recyclage du plutonium, inspiré des études menées dans le cadre de la loi de 2006 sur la gestion des matières et déchets radioactifs. Une illustration des possibilités de la méthodologie est réalisée sur ce scénario, et permet notamment de démontrer le caractère optimal du scénario issu des études menées selon cette loi vis-à-vis de la limitation de l’entreposage de matières fissiles. Ce résultat souligne l’importance de la mise en œuvre d’une gestion dynamique du plutonium via le recours au combustible MOX pour le déploiement progressif des RNR

Signification et validité du test de marche de 6 minutes dans la sclérodermie systémique

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A PROPOS DES TROUBES CHRONOLOGIQUES DE L'ERUPTION DENTAIRE

PARIS7-Odontologie (751062104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF