Institute for Radiation Protection and Nuclear Safety (IRSN)
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The Secretome of Human Dental Pulp Stem Cells and Its Components GDF15 and HB-EGF Protect Amyotrophic Lateral Sclerosis Motoneurons against Death
No full textInternational audienceAmyotrophic lateral sclerosis (ALS) is a fatal and incurable paralytic disorder caused by the progressive death of upper and lower motoneurons. Although numerous strategies have been developed to slow disease progression and improve life quality, to date only a few therapeutic treatments are available with still unsatisfactory therapeutic benefits. The secretome of dental pulp stem cells (DPSCs) contains numerous neurotrophic factors that could promote motoneuron survival. Accordingly, DPSCs confer neuroprotective benefits to the SOD1 G93A mouse model of ALS. However, the mode of action of DPSC secretome on motoneurons remains largely unknown. Here, we used conditioned medium of human DPSCs (DPSCs-CM) and assessed its effect on survival, axonal length, and electrical activity of cultured wildtype and SOD1 G93A motoneurons. To further understand the role of individual factors secreted by DPSCs and to circumvent the secretome variability bias, we focused on GDF15 and HB-EGF whose neuroprotective properties remain elusive in the ALS pathogenic context. DPSCs-CM rescues motoneurons from trophic factor deprivation-induced death, promotes axon outgrowth of wildtype but not SOD1 G93A mutant motoneurons, and has no impact on the spontaneous electrical activity of wildtype or mutant motoneurons. Both GDF15 and HB-EGF protect SOD1 G93A motoneurons against nitric oxide-induced death, but not against death induced by trophic factor deprivation. GDF15 and HB-EGF receptors were found to be expressed in the spinal cord, with a two-fold increase in expression for the GDF15 low-affinity receptor in SOD1 G93A mice. Therefore, the secretome of DPSCs appears as a new potential therapeutic candidate for ALS
En quête d'archives : Tchernobyl par l'image, le point de vue soviétique
No full textL’IRSN dispose dans ses archives de nombreuses cassettes vidéo au format VHS encore non numérisées. Parmi celle-ci, une vidéo intitulée « 26 avril 1986 » a intrigué Michaël Mangeon, consultant et chercheur associé au laboratoire Environnement Ville Société (EVS) de l’université de Lyon.Cette vidéo de 15 min présente le déroulé de l’accident nucléaire de Tchernobyl et quelques vues post-accidentelles. Présentée par une voix-off masculine française avec un fort accent russe, elle est introduite par un Copyright du Comité d'Etat de l'Union soviétique pour l'utilisation de l'énergie atomique. Accompagné de l’archiviste Camille Bouchain, Michaël Mangeon a mené l’enquête pour le service de partage de la connaissance et de l’archivage (SEARCH) de l’IRSN et réalisé une étude pour répondre à une série de questions : d’où vient cette vidéo ? Dans quel contexte a-t-elle été produite ? Pourquoi s’est-elle retrouvée dans les archives de l’IRSN ? Que contient ce film ?L’idée est donc de réaliser une analyse et de valoriser cette archive remarquable de l’IRSN. Pour analyser cette vidéo, en plus de la littérature disponible sur le sujet, ce travail a mobilisé des archives de l’IRSN, d’EDF et de l’AIEA
Reconstructing a River Temporal Trajectory Through the Metal Composition of Historical Floodplain Deposition (Upper Rhine)
No full textInternational audienceReconstructing temporal evolution of geochemical composition of highly anthropized rivers is essential to evaluate and model the impact of regulations taken to reduce water pollution but also to predict their future trajectory. Hydrogeochemical monitoring performed by water agencies only goes back to a few decades (> 80’s). Moreover, datasets usually are heterogeneous and merely focus on a few contaminants of environmental concern at that time. Geochemical analysis of well-dated floodplain sediments allows reconstructing the chemical evolution of rivers over the last century -or more- since most contaminants associate with solid particles transferred by rivers. The potential of this approach is illustrated in this study by the accurate dating and analysis of fine sediments collected along a 105 cm-deep profile from the Upper Rhine floodplain (Rhinau Island). The combination of historical planimetric (old maps) and hydrological data with geochronological constraints (IRSL single grain, 137Cs, 210Pb xs ) provides a robust chronological framework for this sedimentary archive. The analysis of major and trace element concentrations within the collected sediments highlight metal enrichments along the profile (e.g., Pb, Zn, Cu). For most of them, enrichments reached a maximum in the late 1970s-early 1980s followed by a decrease until today, although enrichment peaks may have been earlier for some other metals. For metals such as Pb, Zn and Cu, the progressive decrease from 1980s likely results from both the evolution of human activities in the upstream basin as well as the implemented regulations reducing industrial and urban metallic releases into the Rhine River. We suggest here that interdisciplinary studies of fluvial sedimentary archives, including hydro-geomorphology, can greatly help reconstructing the history of metal pollution in the world's largest rivers and to understand their evolution in response to human pressure, including industrial, urban and agricultural activities
Influence of non-equilibrium and nonlinear sorption of 137Cs in soils. Study with stirred flow-through reactor experiments and quantification with a nonlinear equilibrium-kinetic model
No full textInternational audienceThis paper addresses the modelling of cesium sorption in non-equilibrium and nonlinear conditions with a two-site model. Compared to the classical Kd approach, the proposed model better reproduced the breakthrough curves observed during continuous-flow stirred tank reactor experiments conducted on two contrasted soils. Fitted parameters suggested contrasted conditions of cesium sorption between 1) equilibrium sites, with low affinity and high sorption capacity comparable to CEC and 2) non-equilibrium sites, with a fast sorption rate (half-time of 0.2–0.3 h), a slow desorption rate (half-time of 3–9 days) and a very low sorption capacity (0.02–0.04% of CEC). Comparison of EK sites densities with sorption capacities derived from the literature suggests that the EK equilibrium and kinetic sites might correspond to ion exchange and surface complexation of soil clay minerals respectively. This work stresses the limits of the Kd model to predict 137Cs sorption in reactive transport conditions and supports an alternative non-equilibrium nonlinear approach
Long-term hydromechanical behaviour of a deep cavity taking into account a simplified sequence of life stages
No full textInternational audienceThis study first presents an analytical approach for the hydromechanical behaviour of a deep spherical cavity during different stages of its simplified life cycle. The underground cavity is assumed to be excavated in a dilatant poro-viscoplastic rock mass, and viscoplasticity is modelled based on the Perzyna’s overstress concept. The dilation is incorporated by assuming that the volumetric viscoplastic strain rate is a linear function of the Frobenius norm of the deviatoric plastic strain rate. Some numerical examples are performed to examine the applicability of the model. Then, a sensitivity analysis is conducted on the time-dependent development of the Excavation Damaged Zone (EDZ) around an unsupported deep cavity. The von Mises equivalent strain is used as a criterion to assess the time–dependent extension of the damaged area. The conclusions provide some useful guidelines for the engineering design of underground openings
Brain cancer after radiation exposure from CT examinations of children and young adults: results from the EPI-CT cohort study
No full textInternational audienceSummaryBackground The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer.Methods We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination.Findings We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4–10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51–2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36–2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded.Interpretation The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible
An Elliptic Blending explicit algebraic Reynolds-stress model for wall-bounded flows
No full textA new explicit algebraic Reynolds stress model is derived based on the elliptic blending strategy to account for near-wall blocking effects. The resulting model inherits some of the most important features of the underlying elliptic blending Reynolds stress model, especially the two-component limit of turbulence, but involves only one elliptic equation for the blending coefficient in addition to the standard two-equation k-ε model which serves here as a platform for the model. The algebraic relationship is developed following a direct solution method for two-and three-dimensional mean flows rather than using a projection over a truncated integrity basis. The resulting algebraic relation remains formally similar to standard expressions based on a linear pressure-strain model with the addition of a tensor related to wall orientation. An analytical solution of the nonlinear consistency equation for the production to dissipation ratio is provided for two-dimensional cases that serves as an initial guess to an iterative approach depending on the flow situation. The computations carried out on fully developed turbulent flows to validate the algebraic model demonstrate the good model performances and confirm the effectiveness of the iterative approach to reach self consistency
Analyse de la relation entre le risque de cancer et l'exposition médicale diagnostique aux rayonnements ionisants pendant l'enfance, au sein de la cohorte « Enfant Scanner »
No full textComputed tomography (CT) has been used increasingly over the last decades. However, concerns have been raised about potentially radiation-related cancer risks, particularly after exposure to CT in childhood, due to the greater radiation sensitivity of children. The French CT cohort includes almost 100,000 children who received at least one CT between 2000 and 2011 in one of the 21 participating university hospitals. Examinations and radiological protocols were retrieved to estimate cumulative absorbed doses. The aim of this work is to estimate accurate cancer risks following CT scans (i.e. central nervous system tumors, leukemia and lymphoma) and their related uncertainties from the French CT cohort data. A first analysis showed a statistically significant positive association between the absorbed organ dose and the incidence of central nervous system tumors and leukemia. However, several sources of uncertainty in the calculation of organ dose exist but have not been accounted for in risk estimates. Bayesian hierarchical models were proposed and compared to simultaneously account for several sources of dose uncertainty when estimating the risk of childhood cancer following CT scans. Finally, we aimed at quantifying the effect of childhood CT exposure on the estimation of the cumulative incidence function of each radiation- induced cancer of interest. For this purpose, we proposed an original Bayesian mixture model accounting for competing risks, a time-dependent exposure covariate and a weak signal in the data.Les enfants présentent une radiosensibilité plus élevée aux rayonnements ionisants (RIs) que les adultes. De plus, il a été observé, ces dernières décennies, une multiplication des examens diagnostiques utilisant les RIs. Cependant, les effets à long terme de ces expositions médicales sont peu connus. La cohorte Enfant Scanner inclut environ 100 000 enfants exposés à au moins un examen scanner entre 2000 et 2011 dans les 21 CHUs participants. Des doses individuelles de RIs attribuables à chaque examen scanner ont été estimées au niveau de la moelle et du cerveau à partir des protocoles utilisés dans les CHUs. L’objectif de cette thèse est d’estimer le plus finement possible les risques de cancers radio-induits (i.e., tumeurs du système nerveux central, leucémie et lymphome) ainsi que l’incertitude associée à partir des données de la cohorte Enfant Scanner. Dans un premier temps, il a été mis en évidence des associations positives statistiquement significatives entre la dose absorbée à l’organe et l’incidence de tumeurs du système nerveux central et de leucémie. Toutefois, l’incertitude sur le calcul de la dose à l’organe n’a pas été considérée dans cette première analyse. Des modèles hiérarchiques bayésiens ont alors été proposés et comparés afin de décrire conjointement différentes sources d’in- certitude inhérentes au calcul de la dose à l’organe et d’en tenir compte dans les estimations du risque de cancer. Enfin, nous souhaitions quantifier l’impact de l’exposition aux examens scanners pendant l’enfance sur l’estimation de la fonction d’incidence cumulée de chaque cancer radio-induit d’intérêt. Nous proposons un modèle de mélange bayésien original qui permet d’apporter une réponse en présence de risques compétitifs, d’une variable d’exposition d’intérêt dépendante du temps et d’un signal faible dans les données disponibles
Response to Tsuda et al. “demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the toolkit for detecting misused epidemiological methods”
No full textInternational audienceBackground The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) European project was conducted in 2015-2017 to review the lessons learned from the experience of past nuclear accidents and develop recommendations for preparedness and health surveillance of populations affected by a nuclear accident. Using a toolkit approach, Tsuda et al. recently published a critical review of the article by Cléro et al. derived from the SHAMISEN project on thyroid cancer screening after nuclear accident. Main body We address the main points of criticism of our publication on the SHAMISEN European project. Conclusion We disagree with some of the arguments and criticisms mentioned by Tsuda et al. We continue to support the conclusions and recommendations of the SHAMISEN consortium, including the recommendation not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it
The extremely shallow Mw 4.9 2019 Le Teil earthquake, France: main ground motion features highlighted by comparison with ground motion models
No full textInternational audienceOn November 11th, 2019, a moderate Mw 4.9 earthquake occurred in Le Teil in the southeast of France, inducing significant damage (VIII on the EMS98 intensity scale in some localities). This moderate earthquake occurred at a very shallow depth of 1-2 km and induced a surface rupture up to 15 cm uplift. Good quality recordings of this earthquake are available at numerous stations well distributed around the epicentre, with the nearest station 8 km from the rupture. These recordings were analysed to highlight any specific ground motion features related to the shallow depth of the earthquake with a focus on the residuals between observations and ground motion model predictions. The first trend emerging from the residual analysis is that observations are higher than predictions at 0.5 Hz and on the contrary, they are lower, above 5 Hz. Looking at the spatial distribution of residuals, we highlight that their amplitude is closely related to their location. For example, at high frequencies, residuals are lower for sites in the southeast of France, which is consistent to the first order with regional attenuation maps. Source properties and regional geological characteristics could also be explored to explain the residual amplitudes in different frequency ranges. Finally, different phenomena could be involved to explain residuals, but it is not straightforward to conclude that one factor is dominant