Rapport final du projet européen CatClay sur les processus de migration des cations dans les roches argileuses indurées

International audienceIn the framework of the feasibility studies on the radioactive waste disposal in deep argillaceous formations, it isnow well established that the transport properties of solutes in clay rocks, i.e. parameter values for Fick’s law, are mainlygoverned by the negatively charged clay mineral surface. While a good understanding of the diffusive behaviour of non-reactiveanionic and neutral species is now achieved, much effort has to be placed on improving understanding of coupledsorption/diffusion phenomena for sorbing cations. Indeed, several cations known to form highly stable surface complexes withsites on mineral surfaces migrate more deeply into clay rock than expected. Therefore, the overall objective of the EC CatClayproject is to address this issue, using a ‘bottom-up’ approach, in which simpler, analogous systems (here a compacted clay,‘pure’ illite) are experimentally studied and modelled, and then the transferability of these results to more complex materials, i.e.the clay rocks under consideration in France, Switzerland and Belgium for hosting radioactive waste disposal facilities, isverified. The cations of interest were chosen for covering a representative range of cations families: from a moderately sorbingcation, the strontium, to three strongly sorbing cations, Co(II), Zn(II) and Eu(III). For the 4 years of this project, much effort wasdevoted to developing and applying specific experimental methods needed for acquiring the high precision, reliable data neededto test the alternative hypotheses represented by different conceptual-numerical models. The enhanced diffusion of the sorbingcations of interest was confirmed both in the simpler analogous illite system for Sr2+, Co(II) and Zn(II), but also in the naturalclay rocks, except for Eu(III). First modelling approach including diffusion in the diffuse double layer (DDL) promisinglysucceeded in reproducing the experimental data under the various conditions both in illite and clay rocks, even though someassumptions made have to be verified. In parallel, actual 3D geometrical pore size distributions of compacted illite, and in lessextent, clay rock samples, were successfully determined by combining TEM and FIB-nt analyses on materials maintained in awater-like saturation state by means of an extensive impregnation step. Based on this spatial distribution of pores, first numericaldiffusion experiments were carried at the pore scale through virtual illite, enabling a better understanding of how transferpathways are organized in the porous media. Finally, the EC CatClay project allowed a better understanding of the migration ofstrongly sorbing tracers through low permeability ‘clay rock’ formations, increasing confidence in our capacity to demonstratethat the models used to predict radionuclide migration through these rocks are scientifically sound

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian childhood obesity treatment trial (MASCOT)

Context. Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. Aim. To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. Methods. Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). Results. The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. Conclusions. Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes

Impact of Periodic Current Pulses on Li-Ion Battery Performance

International audiencePulse charging and pulse discharging have been reported by many authors in the literature to improve the performance of various secondary electrochemical cells. Only a few authors mentioned the effects of such charge and discharge method on lithium-ion batteries. The overall objective of this work is to experimentally investigate the impact of certain current pulse profiles on the electrical performance of Li-ion batteries. The results highlight a detrimental impact of periodic pulses on the cell performance compared to profiles with constant current

Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin.

The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not

Effect of a Successful Intensive Lifestyle Program on Insulin Sensitivity and Glucose Tolerance in Obese Youth

OBJECTIVE—To evaluate the impact on glucose metabolism of a lifestyle program (the Yale Bright Bodies Program) for obese children

Measuring the Similarity of Single Molecular Localisation Microscopy Derived Marked Point-Clouds

Cellular membranes are dynamic, heterogeneous structures where lipid nanodomains (e.g., lipid rafts) play key roles in signalling, membrane trafficking, and protein function. Single-Molecule Localisation Microscopy (SMLM) reveals the spatial organisation of these nanoscale features; however, traditional analyses focus only on spatial patterns and neglect biochemical and biophysical properties critical for membrane function. By combining SMLM with environmentally sensitive fluorescent probes, such as di-4-ANEPPDHQ, we can produce marked point patterns which couple spatial coordinates with environmental information, such as membrane lipid order quantified by generalised polarisation (GP) values. Unfortunately, existing methods do not adequately compare these complex datasets. Here, we introduce a new method, which assesses the similarities of marked point patterns by considering the spatial arrangement as well as the biophysical properties of the data. The method computes three semi-independent Kolmogorov-Smirnov scores which are used to map comparisons between two point-clouds in 3D space. This allows the distance to the origin of a comparison to be used as a metric for similarity. Application to simulated data confirms the reliability of the method, while application to experimental GP-marked point patterns identifies condition-dependent variations in lipid order. This framework thus offers a versatile tool for the study of biochemical and biophysical properties of cellular nano-environments, enabling new insight into membrane organisation and function.</p

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

First numerical analysis of runaway electron generation in tungsten-rich plasmas towards ITER

The disruption and runaway electron analysis model code was extended to include tungsten impurities in disruption simulations with the aim of studying the runaway electron (RE) generation. This study investigates RE current sensitivity on the following plasma parameters and modelling choices: tungsten concentration, magnetic perturbation strength, electron modelling, thermal quench time and tokamak geometry: ITER-like or ASDEX-like. Our investigation shows that a tungsten concentration below 10-3 does not cause significant RE generation on its own. However, at higher concentrations it is possible to reach a very high RE current. Out of the two tested models of electrons in plasma: fluid and isotropic (kinetic), results from the fluid model are more conservative, which is useful when it comes to safety analysis. However, these results are overly pessimistic when compared to the isotropic model, which is based on a more reliable approach. Our results also show that the hot-tail RE generation mechanism is dominant as a primary source of RE in tungsten induced disruptions, usually providing orders of magnitude higher RE seed than Dreicer generation. We discuss best practices for simulations with tungsten-rich plasma, present the dependence of the safety limits on modelling choices and highlight the biggest shortcoming of the current simulation techniques. The obtained results pave the way for a wider analysis of tungsten impact on the disruption dynamics, including the mitigation techniques for ITER in the case of strong contamination of the plasma with tungsten