Impact of electrostatic potential on microcapsule-formation and physicochemical analysis of surface structure:Implications for therapeutic cell-microencapsulation

Cell-encapsulation is used for preventing therapeutic cells from being rejected by the host. The technology to encapsulate cells in immunoprotective biomaterials, such as alginate, commonly involves application of an electrostatic droplet generator for reproducible manufacturing droplets of similar size and with similar surface properties. As many factors influencing droplet formation are still unknown, we investigated the impact of several parameters and fitted them to equations to make procedures more reproducible and allow optimal control of capsule size and properties. We demonstrate that droplet size is dependent on an interplay between the critical electric potential (Uc,), the needle size, and the distance between the needle and the gelation bath, and that it can be predicted with the equations proposed. The droplet formation was meticulously studied and followed by a high-speed camera. The X-ray photoelectron analysis demonstrated optimal gelation and substitution of sodium with calcium on alginate surfaces while the atomic force microscopy analysis demonstrated a low but considerable variation in surface roughness and low surface stiffness. Our study shows the importance of documenting critical parameters to guarantee reproducible manufacturing of beads with constant and adequate size and preventing batch-to-batch variations

Rapport final du projet VERT. Le vélo évalué en rabattement dans les territoires. Volume 1

This report is the final report of project VERT (evaluation of the bicycle as a feeder mode to rail outside urban areas). The VERT project aims at studying bicycle use as a feeder mode to railway stations, for regular use, in exurban areas. It focuses first on a state of the art fostered by international and French experience, providing quantitative and qualitative elements for research (T2), second on economic analysis (T3) implemented in several modeled scenarios (T4), making it possible to compare bike and ride solutions with park and ride solutions, and to draw a cost-benefit analysis for users and the community. Third, project includes qualitative analyses (T5) backed by interviews with stakeholders, and is applied in a case study in Amboise (T6), comparing scenarios for developing the bicycle as a feeder mode to train, built from observations of present situation, software development to map catchment areas of bicycles and pedelecs,analysing feeder routes and computing the cost-benefit balance of bike and ride. This very positive balance as well as other results show that the Amboise site possesses characteristics enabling this intermodal development, that are supported by some local stakeholders' projects. This confirms that this intermodal potential must be backed by local policies, as shown by experience in other regions or in other countries.Ce rapport est le rapport final du projet VERT (le vélo évalué en rabattement dans les territoires). Le projet VERT vise à étudier l'utilisation du vélo comme mode d'accès aux gares, pour un usage régulier, dans le milieu périurbain. Il se concentre sur un état de l'art nourri d'expériences étrangères et françaises, fournissant des éléments quantitatifs et qualitatifs pour la recherche (T2), sur un bilan économique (T3) mis en oeuvre dans plusieurs scénarios modélisés (T4) permettant de comparer les solutions de vélo+train à des solutions de voiture+train, et d'en établir un bilan économique pour l'usager et pour la collectivité. Le projet inclut aussi des analyses qualitatives (T5) appuyées par des entretiens avec les acteurs, et comporte une étude de cas sur le terrain d'Amboise (T6), comparant plusieurs scénarios de développement du vélo en rabattement sur la gare, construits à partir d'observations de la situation actuelle, du développement de logiciel cartographiant les zones atteintes par le vélo et le VAE (vélo à assistance électrique), analysant des itinéraires de rabattement et établissant un bilan économique de l'intermodalité vélo-TC. Ce bilan très positif et les autres résultats montrent que le site d'Amboise possède des caractéristiques permettant de développer cette intermodalité, confortées par les projets de certains acteurs locaux. Cela confirme que le potentiel de cette intermodalité doit être appuyé par les politiques locales, comme l'ont montré les expériences d'autres régions ou d'autres pays

Congélation de produits alimentaires : amélioration de la cristallisation par applications de micro-ondes

National audienceLa qualité d'un produit congelé est liée à la cristallisation ; en règle générale, plus la taille des cristaux de glace est petite, meilleure sera la qualité du produit. Un procédé innovant a été évalué dans le cadre du projet européen (FREEZEWAVE). Une assistance micro-ondes (2450 MHz) a été utilisée pour perturber le changement d'état de l'eau. Sur un prototype de laboratoire, les expériences ont confirmé que, quels que soient le mode d'application des micro-ondes et les paramètres du procédé, on observe une réduction de la taille des cristaux. Cet impact positif a été obtenu sur diverses matrices alimentaires, dont des pommes de terre. Un modèle de prédiction a par ailleurs permis de qualifier ces cinétiques. Deux concepts sont avancés pour expliquer ces effets bénéfiques. Abstract FREEZEWAVE project (SUSFOOD ERA-net project 2015-2018

Mémento pour la gestion des projets d'assainissement : fascicule 3 : les eaux pluviales

Ce fascicule aborde la gestion des eaux pluviales à deux niveaux : celui de la planification, du fait de l’importance de cette réflexion amont (fiche « enjeux d’urbanisme et d’aménagement »), et celui du projet d'aménagement, public ou privé, de type rénovation urbaine, création de lotissement, de ZAC, de zone industrielle, … Il ne traite pas le projet pluvial "isolé" du projet d'aménagement (création ou réhabilitation de collecteur, dispositif de traitement des eaux pluviales, …). Il insiste sur l’importance de prendre en compte la gestion des eaux pluviales très à l’amont du projet et en associant très tôt l’ensemble des acteurs de l’aménagement

Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

A majority of MRI procedures requiring intravascular injections of contrast agents are performed with paramagnetic chelates. Such products induce vascular signal enhancement and they are rapidly excreted by the kidneys. Unfortunately, each chelate is made of only one paramagnetic ion, which, taken individually, has a limited impact on the MRI signal. In fact, the detection of molecular events in the nanomolar range using T-1-weighted MRI sequences requires the design of ultra-small particles containing hundreds of paramagnetic ions per contrast agent unit. Ultra-small nanoparticles of manganese oxide (MnO, 6-8 nm diameter) have been developed and proposed as an efficient and at least 1000 x more sensitive “positive” MRI contrast agent. However no evidence has been found until now that an adequate surface treatment of these particles could maintain their strong blood signal enhancement, while allowing their rapid and efficient excretion by the kidneys or by the hepatobiliairy pathway. Indeed, the sequestration of MnO particles by the reticuloendothelial system followed by strong uptake in the liver and in the spleen could potentially lead to Mn2+-induced toxicity effects. For ultra-small MnO particles to be applied in the clinics, it is necessary to develop coatings that also enable their efficient excretion within hours. This study demonstrates for the first time the possibility to use MnO particles as T-1 vascular contrast agents, while enabling the excretion of > 70% of all the Mn injected doses after 48 h. For this, small, biocompatible and highly hydrophilic pegylated bis-phosphonate dendrons (PDns) were grafted on MnO particles to confer colloidal stability, relaxometric performance, and fast excretion capacity. The chemical and colloidal stability of MnO@PDn particles were confirmed by XPS, FTIR and DLS. The relaxometric performance of MnO@PDns as “positive” MRI contrast agents was assessed (r(1) = 4.4 mM(-1) s(-1), r(2)/r(1) = 8.6; 1.41 T and 37 degrees C). Mice were injected with 1.21 mu g Mn per kg (22 mu mol Mn per kg), and scanned in MRI up to 48 h. The concentration of Mn in key organs was precisely measured by neutron activation analysis and confirmed, with MRI, the possibility to avoid RES nanoparticle sequestration through the use of phosphonate dendrons. Due to the fast kidney and hepatobiliairy clearance of MnO particles conferred by PDns, MnO nanoparticles can now be considered for promising applications in T1-weighted MRI applications requiring less toxic although highly sensitive “positive” molecular contrast agents

Antilymphocyte globulin for matched sibling donor transplantation in patients with myelofibrosis

The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft-versus-host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n= 287). The cumulative incidences of grade II-IV acute graft-versus-host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft-versus-host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft-versus-host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P= 0.010) while it did not decrease the risk of chronic graft-versus-host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P-values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft-versushost disease without increasing the risk of relapse.Peer reviewe

Effectiveness of Chest Physiotherapy in Infants Hospitalized with Acute Bronchiolitis: A Multicenter, Randomized, Controlled Trial

Vincent Gajdos and colleagues report results of a randomized trial conducted among hospitalized infants with bronchiolitis. They show that a physiotherapy technique (increased exhalation and assisted cough) commonly used in France does not reduce time to recovery in this population

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Stratégies d'enseignement et d'apprentissage dans une séquence bilingue anglais/français en sciences à l'école primaire (Niveau CM2)

On the basis of an analysis of the benefits of a bilingual approach to language teaching and strategies for second language learning, the aim of the study is to optimise this approach in primary schools for the benefit of all pupils. A post-experimental synthesis after three years of CLIL in different disciplines, raises questions about this innovative and original approach. During an initiation class, pupils at CM2 level are invited to reflect on the strategies they can develop to use, understand and produce language in English, as well as to adhere to a didactic contract with the teacher involving rules about aspects such as code-switching and their confidence. Concommitantly, the teacher deploys efficient bilingual teaching strategies to ensure pupils progress in the two integrated disciplines. The results are shown to be positive for writing, slightly ambiguous for speaking, but nonetheless convincing that the initiation ought to be prolonged for confirmation.Après avoir exploré et analysé l’intérêt et les particularités de l’enseignement bilingue puis les stratégies d’apprentissage d’une langue seconde, l’objectif est de chercher les moyens d’optimiser cet enseignement à l’école primaire afin que tous les élèves puissent en bénéficier et progresser. La synthèse et l’examen à postériori de trois ans d’expérimentation d’enseignement de plusieurs DNL en tant qu’enseignante d’une école entrée dans le dispositif EMILE amène un certain nombre de questions inhérentes à cet enseignement novateur et original. Lors d’une séquence d’initiation, les élèves d’une classe de CM2 sont amenés à réfléchir aux stratégies d’apprentissage qu’ils pourront développer et utiliser pour comprendre et produire en anglais ainsi qu’à établir un contrat didactique avec l’enseignant comprenant des règles sur des sujets comme l’alternance codique ou leur mise en confiance. De façon concomitante, l’enseignant s’efforce d’utiliser des stratégies d’enseignement efficaces pour profiter au mieux des ressorts de l’enseignement bilingue pour faire progresser les élèves dans les deux disciplines intégrées. Les résultats obtenus se révèlent très positifs à l’écrit, en demi-teinte à l’oral mais montrent que cette initiation aurait tout intérêt à être prolongée pour qu’elle prenne tout son sens

X-ray microtomography to study the baking of bread. A dynamic approach to follow crust and crumb formation

International audienc