Search

Objectif : Évaluer la satisfaction des usagers du Samu 47 à la suite de leur appel dans le cadre de l’aide médicale urgente. Matériel et méthodes : Étude de cohorte observationnelle, monocentrique, prospective, menée entre le 25 août et le 13 septembre 2020 par un même opérateur, à partir d’un questionnaire téléphonique. Le critère de jugement principal était le niveau de satisfaction générale des requérants après leur appel. Les critères secondaires étaient le ressenti du délai de décroché ARM (assistant de régulation médicale) et médical, le niveau de satisfaction de la prise en charge ARM et médicale, le ressenti du délai d’arrivée des effecteurs envoyés, le niveau de satisfaction de leur prise en charge, la mise en application du conseil formulé par le médecin régulateur et la suggestion d’axes d’amélioration. Résultats : Parmi les 596 requérants inclus, 419 (70 %) étaient « très satisfaits », 132 (22 %) « assez satisfaits », 25 (4 %) « peu satisfaits » et 20 (3 %) « pas du tout satisfaits ». Les analyses univariées montraient que cela était lié à l’entretien avec l’ARM et le médecin régulateur, à la prise en charge des secours, à certaines attentes, à la suite donnée à l’appel, au délai ressenti d’arrivée des secours et au délai ressenti de décroché. L’analyse multivariée révélait que les éléments liés à l’insatisfaction étaient l’attente « faire venir les secours » (RC : 5,71, IC 95 % : 2,56–13,01), le fait de recevoir un conseil à l’issue de l’appel (RC : 9,28, IC 95 % : 4,15–21,96) et le délai ressenti de décroché de l’appel jugé « long » (RC : 3,64, IC 95 % : 1,06–10,75). Conclusion : Les usagers sont globalement satisfaits à la suite de leur appel au Samu 47.

BOLD variability (SDBOLD) has emerged as a unique measure of the adaptive properties of neural systems that facilitate fast, stable responding, based on claims that SDBOLDis independent of mean BOLD signal (meanBOLD) and a powerful predictor of behavioural performance. We challenge these two claims. First, the apparent independence of SDBOLDand meanBOLDmay reflect the presence of deactivations; we hypothesize that while SDBOLDmay not be related to raw meanBOLDit will be linearly related toabsolutemeanBOLD. Second, the observed relationship between SDBOLDand performance may be an artifact of using fixed-length trials longer than response times. Such designs provide opportunities to toggle between on- and off-task states, and fast responders likely engage in more frequent state-switching, thereby artificially elevating SDBOLD. We hypothesize that SDBOLDwill be higher and more strongly related to performance when using such fixed-length trials relative to self-paced trials that terminate upon a response. We test these two hypotheses in an fMRI study using blocks of fixed-length or self-paced trials. Results confirmed both hypotheses: (1) SDBOLDwas robustly related withabsolutemeanBOLD; and (2) toggling between on- and off-task states during fixed-length trials reliably contributed to SDBOLD. Together, these findings suggest that a reappraisal of the functional significance of SDBOLDas a unique marker of cognitive performance is warranted.

The influence of a Ni plating surface treatment on transient liquid phase bonding (TLPB) of superalloys was investigated through a comparison of BNi-2 filler metal joints made with IN718 base metals (BM) with and without a Ni plating surface treatment. Interdiffusion between the BM and Ni plating occurred during initial heating, creating a compositional gradient at the faying surface. This resulted in the formation of a boride free denuded zone immediately below the BM faying surface. In parallel, the Ni plating acted as a diffusion barrier against the filler metal, preventing BM dissolution (BMD). The lack of BMD was accompanied by a reduced initial boron uptake by the BM and little gap widening in Ni-plated samples. The rate of IS was approximately the same regardless of surface preparation. Overall, the presence of a Ni plating reduced the time to complete isothermal solidification by approximately 25 pct, primarily due to the prevention of BMD and the associated gap widening.

Motile cells such as immune and cancer cells experience large deformation events that result from the physical constraints they encounter while migrating within tissues or circulating between organs. It has become increasingly clear that these cells can survive and adapt to these changes in cell shape using dedicated shape sensing pathways. However, how shape sensing impacts their function and fate remains largely unknown. Here we identify a shape sensing mechanism that couples cell motility to expression of CCR7, the chemokine receptor that guides immune cells to lymph nodes. We found that this mechanism is controlled by the lipid metabolism enzyme cPLA2, requires an intact nuclear envelop and exhibits an exquisitely sensitive activation threshold tuned by ARP2/3 and its inhibitor Arpin. We further show that shape sensing through the ARP2/3-cPLA2axis controls Ikkβ-NFκB-dependent transcriptional reprogramming of dendritic cells, which instructs them to migrate to lymph nodes in an immunoregulatory state compatible with their homeostatic tolerogenic function. These results highlight that the cell shape changes experienced by motile cells evolving within the complex environment of tissues can dictate their behavior and fate.

Funding Information: This material is based upon work supported by the US Department of Energy, Office of Science, Office of Fusion Energy Sciences, using the DIII-D National Fusion Facility, a DOE Office of Science user facility, under Awards DE-FC02-04ER54698 and DE-AC52-07NA27344. Publisher Copyright: © 2022 IAEA, Vienna. DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.

The influence of chromium and iron’s absence (BNi-3) and presence (BNi-2) in boron-containing filler metals (FM) on the TLPB behavior of IN718 base metal (BM) was examined. Results indicate that the absence of Cr and Fe in the FM significantly aggravated BM dissolution and gap widening, particularly when similar degrees of brazing beyond the FM liquidus temperature occurred. This led to a higher complete isothermal solidification time, despite a higher rate of isothermal solidification (IS) and initial boron uptake displayed by the IN718/BNi-3 joint. EDS and quantitative image analysis performed within the DAZ concluded that differences observed in the rate of IS were related to the amount and type of borides forming in the DAZ. The lack of Cr in the BNi-3 favored the formation of Cr-poor:B-rich Cr(Mo,Nb)B borides, leading to a higher rate of B uptake by the base metal. Joints made from the Cr containing BNi-2 FM displayed a combination of Cr-rich:B-poor CrB and Cr(Mo,Nb)B borides leading to lower rates of B uptake.

The TLPB behavior of Ni/Ni-Si-B and Ni-Cr-Fe/Ni-Si-B base metal/braze joints was examined to determine the role chromium in the base metal has during joining of Ni-based alloys using a boron-bearing braze metal. The isothermal solidification (IS) rate in these two braze joints at 1075 °C was measured using DSC. Microstructural evolution within the diffusionally affected zone (DAZ) was examined both in terms of the type of borides formed and their volume fraction, using image analysis and phase equilibria predictions. Overall, the results show that when the base metal (BM) contains an appreciable concentration of Cr the IS rate decreases significantly. This was due to the formation of a low volume fraction of CrB within the DAZ, dictated by phase equilibria. Conversely, in the pure Ni base metal (BM) the thermodynamically favored boride was Ni3B, present at high volume fractions, resulting in rapid IS. A direct link between the boride microstructure of the DAZ and the rate of IS was established.

The present work details a quantitative investigation into the braze gap width dependence on the initial boron uptake (IBU) phenomena—an event which manifests during the initial stages of brazing of boron-containing filler metals. This was accomplished using in situ cyclic DSC of both full- and half-joint TLPB couples, i.e., IN625/xBNi2/IN625 and IN625/xBNi2. All joints demonstrated a linear relationship between the isothermally solidified gap width with the square root of time which were in excellent agreement with conventional metallographic analysis methods. A conceptual model designed to quantify both the extent of isothermal solidification and IBU during TLPB in terms of the redistribution of boron as borides was implemented. The investigation demonstrated excellent agreement with microstructural and DSC results further supporting the crucial role boride formation has on the kinetics of TLPB.

Summary Dendritic cells (DCs) patrol tissues and transport antigens to lymph nodes to initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population composed of distinct subsets that can exhibit different activation states and functions. How tissue-specific cues orchestrate DC diversification remains elusive. Here, we show that the small intestine included two pools of cDC2s originating from common pre-DC precursors: (1) lamina propria (LP) CD103+CD11b+ cDC2s that were mature-like proinflammatory cells and (2) intraepithelial cDC2s that exhibited an immature-like phenotype as well as tolerogenic properties. These phenotypes resulted from the action of food-derived retinoic acid (ATRA), which enhanced actomyosin contractility and promoted LP cDC2 transmigration into the epithelium. There, cDC2s were imprinted by environmental cues, including ATRA itself and the mucus component Muc2. Hence, by reaching distinct subtissular niches, DCs can exist as immature and mature cells within the same tissue, revealing an additional mechanism of DC functional diversification., Graphical abstract, Highlights • Epithelial colonization by gut cDC2s leads to their transcriptional reprograming • Unlike lamina propria cDC2s, intraepithelial cDC2s show an immature-like phenotype • Intraepithelial cDC2s trigger T cell hyporesponsiveness • The phenotype of intraepithelial cDC2s is imprinted by both retinoic acid and mucus, Gut cDC2s have been described to migrate into the epithelium, but whether this event modifies their phenotype is unknown. Rivera et al. show that upon epithelium colonization, cDC2s adopt an immature-like phenotype, revealing the existence of subtissular niches able to shape cDCs' fate and function.

International audience; Cell migration is an essential process that controls many physiological functions ranging from development to immunity. In vivo, cells are guided by a combination of physical and chemical cues. Chemokines have been the center of attention for years, but the role of physical properties of tissues has been under-investigated. This despite the fact that these properties can be drastically modified in pathology. Here, we discuss the role of one important tissue physical property, hydraulic resistance, in cell guidance, a phenomenon referred to as barotaxis, and describe the underlying physical principles and molecular mechanisms. Finally, we speculate on the putative role of barotaxis in physiological processes involving immune and cancer cells.

Dendritic cells (DCs) devoid of the actin regulator Wiskott-Aldrich syndrome protein (WASp) show reduced directed migration and decreased formation of podosome adhesion structures. We examined DCs expressing a gain-of-function mutation in WASp, WASp L272P, identified in X-linked neutropenia patients. Analysis of WASp L272P DCs was compared to WASp-deficient DCs to examine how WASp activity influences DC migratory responses. In confined space, WASp-deficient DCs had increased migration speed whereas WASp L272P DCs had similar average speed but increased speed fluctuations, reduced displacement, and atypical rounded morphology, compared to wild-type (WT) DCs. Using an ear inflammation model and flow cytometry analysis, WT, WASp-deficient, and WASp L272P DCs were found to migrate in comparable numbers to the draining lymph nodes (LNs). However, histology analysis revealed that migratory DCs of WASp deficient and WASp L272P mice were mainly located in the collagenous capsule of the LN whereas WT DCs were located inside the LN. Analysis of ultrastructural features revealed that WASp L272P DCs had reduced cell area but formed larger podosome structures when compared to WT DCs. Together, our data suggest that WASp activity regulates DC migration and that loss-of-function and gain-of-function in WASp activity lead to different and phenotype-specific DC migratory behavior.

Diffusion path analysis was applied to the Ni-Si-B system to explain the deviation from classical transient liquid-phase bonding observed when using multicomponent systems containing Boron as a melting point depressant. This was achieved using a combination of differential scanning calorimetry, SEM-EDS microstructural and chemical analysis, and Thermo-Calc modeling software of Ni/Ni-Si-B couples. Compositional analysis identified differing distributions of B and Si across the braze joint which were mapped onto isothermal sections of Thermo-calc-generated phase diagrams. Below 1093 °C, the inevitable formation of diffusionally affected zone (DAZ) and isothermally solidified zone is a direct consequence of the need for phase equilibria in the Ni-Si-B ternary system and is predicted by diffusion path analysis. Above 1100 °C, diffusion path analysis also correctly predicts a persistent liquid phase observed to occur through the melting of the DAZ (i.e., a γ-Ni(Si)-Ni3B eutectic reaction).

Severe acute liver injury is a grave complication of exertional heatstroke. Liver transplantation (LT) may be a therapeutic option, but the criteria for LT and the optimal timing of LT have not been clearly established. The aim of this study was to define the profile of patients who require transplantation in this context.This was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related severe acute liver injury with a prothrombin time (PT) of less than 50%. A total of 24 male patients were studied.Fifteen of the 24 patients (median nadir PT: 35% [29.5-40.5]) improved under medical therapy alone and survived. Nine of the 24 were listed for emergency LT. At the time of registration, the median PT was 10% (5-12) and all had numerous dysfunctional organs. Five patients (nadir PT: 12% [9-12]) were withdrawn from the list because of an elevation of PT values that mainly occurred between day 2 and day 3. Ultimately, 4 patients underwent transplantation as their PT persisted at10%, 3 days (2.75-3.25) after the onset of exertional heatstroke, and they had more than 3 organ dysfunctions. Of these 4 patients, 3 were still alive 1 year later. Histological analysis of the 4 explanted livers demonstrated massive or sub-massive necrosis, and little potential for effective mitoses, characterised by a "mitonecrotic" appearance.The first-line treatment for exertional heatstroke-related severe acute liver injury is medical therapy. LT is only a rare alternative and such a decision should not be taken too hastily. A persistence of PT10%, without any signs of elevation after a median period of 3 days following the onset of heatstroke, was the trigger that prompted LT, was the trigger adopted in order to decide upon LT.Acute liver injury due to heatstroke can progress to acute liver failure with organ dysfunction despite medical treatment; in such situations, liver transplantation (LT) may offer a therapeutic option. The classic criteria for LT appear to be poorly adapted to heatstroke-related acute liver failure. We confirmed thatmedication is the first-line therapy acute liver injury caused by heatstroke, with LT only rarely necessary. A decision to perform LT should not be made hastily. Fluctuations in prothrombin time and the patient's clinical status should be considered even in the event of severe liver failure.

Deep-learning (DL)-based auto-contouring solutions have recently been proposed as a convincing alternative to decrease workload of target volumes and organs-at-risk (OAR) delineation in radiotherapy planning and improve inter-observer consistency. However, there is minimal literature of clinical implementations of such algorithms in a clinical routine. In this paper we first present an update of the state-of-the-art of DL-based solutions. We then summarize recent recommendations proposed by the European society for radiotherapy and oncology (ESTRO) to be followed before any clinical implementation of artificial intelligence-based solutions in clinic. The last section describes the methodology carried out by three French radiation oncology departments to deploy CE-marked commercial solutions. Based on the information collected, a majority of OAR are retained by the centers among those proposed by the manufacturers, validating the usefulness of DL-based models to decrease clinicians' workload. Target volumes, with the exception of lymph node areas in breast, head and neck and pelvic regions, whole breast, breast wall, prostate and seminal vesicles, are not available in the three commercial solutions at this time. No implemented workflows are currently available to continuously improve the models, but these can be adapted/retrained in some solutions during the commissioning phase to best fit local practices. In reported experiences, automatic workflows were implemented to limit human interactions and make the workflow more fluid. Recommendations published by the ESTRO group will be of importance for guiding physicists in the clinical implementation of patient specific and regular quality assurances.

Studies in recent years have shed light on the particular features of cytoskeleton dynamics in immune cells, challenging the classical picture drawn from typical adherent cell lines. New mechanisms linking the dynamics of the membrane–cytoskeleton interface to the mechanical properties of immune cells have been uncovered and shown to be essential for immune surveillance functions. In this Essay, we discuss these features, and propose immune cells as a new playground for cell biologists who try to understand how cells adapt to different microenvironments to fulfil their functions efficiently.

Prolonging overall survival (OS) remains an unmet need in relapsed or refractory multiple myeloma (RRMM). In ELOQUENT-2 (NCT01239797), elotuzumab plus lenalidomide/dexamethasone (ERd) significantly improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd) in patients with RRMM and 1–3 prior lines of therapy (LoTs). We report results from the pre-planned final OS analysis after a minimum follow-up of 70.6 months, the longest reported for an antibody-based triplet in RRMM. Overall, 646 patients with RRMM and 1–3 prior LoTs were randomized 1:1 to ERd or Rd. PFS and overall response rate were co-primary endpoints. OS was a key secondary endpoint, with the final analysis planned after 427 deaths. ERd demonstrated a statistically significant 8.7-month improvement in OS versus Rd (median, 48.3 vs 39.6 months; hazard ratio, 0.82 [95.4% Cl, 0.68–1.00]; P = 0.0408 [less than allotted α of 0.046]), which was consistently observed across key predefined subgroups. No additional safety signals with ERd at extended follow-up were reported. ERd is the first antibody-based triplet regimen shown to significantly prolong OS in patients with RRMM and 1–3 prior LoTs. The magnitude of OS benefit was greatest among patients with adverse prognostic factors, including older age, ISS stage III, IMWG high-risk disease, and 2–3 prior LoTs. © 2020, The Author(s).

Resume Introduction Annona muricata L., aussi appele corossolier, est un arbre fruitier cultive dans les pays tropicaux. Ses fruits, ses feuilles, ses graines et ses racines ont des usages multiples en medecine traditionnelle. La description d’effets anticancereux possibles et l’accessibilite du produit incitent les patients a consommer ce produit en automedication. L’objectif de cette etude est de determiner le taux d’usage du corossol a visee anticancereuse chez les patients traites pour un cancer broncho-pulmonaire. Methodes L’etude a ete realisee dans deux services d’oncologie thoracique du CHU de la Reunion. Le questionnaire etait administre face a face chez tous les patients presentant un cancer broncho-pulmonaire tous stades confondus traites par chimiotherapie ou immunotherapie sur une periode de 6 mois. Resultats Cent questionnaires ont ete recueillis. Soixante-sept patients consomment du corossol. Dans 53,7 % des cas, cette consommation est a visee anticancereuse. Elle est reguliere chez 25 patients. L’ingestion sous forme de feuilles bouillies et bues en tisane est la plus repandue (69,5 %). L’approvisionnement est quasi exclusivement local. Conclusion Un quart des patients traites par chimiotherapie pour un cancer bronchopulmonaire a la Reunion consomment de maniere reguliere du corossol a visee anticancereuse. Les consequences de cette consommation, interactions medicamenteuses ou effets secondaires, meritent d’etre identifiees.

International audience; The function of most immune cells depends on their ability to migrate through complex microenvironments, either randomly to patrol for the presence of antigens or directionally to reach their next site of action. The actin cytoskeleton and its partners are key conductors of immune cell migration as they control the intrinsic migratory properties of leukocytes as well as their capacity to respond to cues present in their environment. In this review we focus on the latest discoveries regarding the role of the actomyosin cytoskeleton in optimizing immune cell migration in complex environments, with a special focus on recent insights provided by physical modeling.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare severe adverse drug-induced reaction with multiorgan involvement. The outcome and prediction of those patients who develop severe acute liver injury (sALI) or acute liver failure (ALF) remain little known.A multicenter retrospective study of patients admitted with a diagnosis of DRESS-related sALI or ALF. Histological review was performed on liver core biopsies from native livers.Sixteen patients (11 women, 5 men; mean age, 39±17.2 years) were classified as having definite (n=13) or probable (n=3) DRESS. At admission, 3 patients had hepatic encephalopathy; median levels of prothrombin time, INR, and total bilirubin were, respectively, 33% (Q1-Q3, 21-41), 2.74 (1.98-4.50), and 94 μmol/L (Q1-Q3, 39.5-243.5). Nine patients received corticosteroid therapy. Overall, 9 patients improved spontaneously and 7 worsened (liver transplantation [LT] (n=5), deceased (n=2)). Transplantation-free and post-LT survival was 56% and 60%, respectively. After LT, DRESS recurrence was observed in 3 of 5 patients. Systemic corticosteroid therapy was not significantly associated with a clinical improvement. In the multivariate analysis, factor V level less than 40% at day 0 and factor V levels of 40% or greater at admission but decreasing at day 2 were associated with worse outcome. Pathological findings (n=7) revealed atypical lymphoid infiltrates, Kupffer cell hyperplasia with erythrophagocytosis, and an inconstant presence of eosinophils.The spontaneous prognosis of patients with sALI/ALF due to DRESS is poor and was not improved by corticosteroid therapy. Histology is helpful to establish diagnosis. Dynamic variables regarding factor V values are predictive of a poor outcome.

Resume Introduction Les nodules en verre depoli sont detectes frequemment avec les nouvelles techniques d’imagerie. Ceux-ci peuvent correspondre a des lesions benignes ou a des lesions precancereuses comme l’hyperplasie adenomateuse atypique, l’adenocarcinome in situ mais aussi a des lesions invasives. Leur presence chez des patients atteints de cancer bronchopulmonaire pose la question de la strategie de traitement et de suivi. Observation Nous rapportons le cas d’une patiente de 72 ans suivie pour un adenocarcinome bronchopulmonaire EGFR mute du lobe superieur droit stade IIB. Son scanner thoracique montre de multiples nodules en verre depoli situes dans le meme lobe que la tumeur primitive mais egalement dans les autres lobes. Sur la piece de lobectomie, l’histologie de deux nodules en verre depoli montre une hyperplasie adenomateuse atypique. Conclusion Les nodules en verre depoli peuvent etre retrouves chez les patients presentant un cancer bronchopulmonaire primitif operable. Ces anomalies peuvent parfois etre multiples et correspondre a des lesions d’hyperplasie adenomateuse atypique mais aussi a des lesions carcinomateuses. La surveillance radiologique reste la norme. La strategie de prise en charge chirurgicale en cas de lesion evolutive reste a definir en particulier en cas de lesions multiples pouvant necessiter des chirurgies de resection iteratives.

A control-oriented, two-timescale, linear, dynamic, response model of the rotational transform ι profile and the normalized beta βN is proposed based on experimental data from the DIII-D tokamak. Dedicated system-identification experiments without feedback control have been carried out to generate data for the development of this model. The data-driven dynamic model, which is both device-specific and scenario-specific, represents the response of the ι profile and βN to the electric field due to induction as well as to the heating and current drive (H&CD) systems during the flat-top phase of an H-mode discharge in DIII-D. The control goal is to use both induction and the H&CD systems to locally regulate the plasma ι profile and βN around particular target values close to the reference state used for system identification. A singular value decomposition (SVD) of the plasma model at steady state is carried out to decouple the system and identify the most relevant control channels. A mixed-sensitivity robust control design problem is formulated based on the dynamic model to synthesize a stabilizing feedback controller without input constraints that minimizes the reference tracking error and rejects external disturbances with minimal control energy. The feedback controller is then augmented with an anti-windup compensator, which keeps the given controller well-behaved in the presence of magnitude constraints in the actuators and leaves the nominal closed-loop system unmodified when no saturation is present. The proposed controller represents one of the first feedback profile controllers integrating magnetic and kinetic variables ever implemented and experimentally tested in DIII-D. The preliminary experimental results presented in this work, although limited in number and constrained by actuator problems and design limitations, as it will be reported, show good progress towards routine current profile control in DIII-D and leave valuable lessons for further advancements in the field.

Introduction : La prise en charge du cancer broncho-pulmonaire (CBP) a ete revolutionnee par la decouverte des alterations moleculaires potentiellement actionnable par des therapies ciblees. La population reunionnaise est cosmopolite et metissee. Les profils moleculaires des patients suivis pour un cancer bronchique non a petites cellules (CBNPC) a la Reunion ne sont pas connus depuis la generalisation du sequencage haut debit. Methode : Cette etude est observationnelle, retrospective, multicentrique et inclut les cas de CBNPC diagnostiques a la Reunion entre le 1er janvier 2017 et le 31 decembre 2018 et ayant beneficie d’une analyse moleculaire au CHU de Bordeaux. L’objectif principal est de determiner la frequence des profils histologiques et biomoleculaires des CBNPC diagnostiques a la Reunion. Resultats : Au total, 310 patients ont beneficie d’un diagnostic de CBNPC et d’une recherche d’alteration moleculaire dont 281 adenocarcinomes (91%). 207 patients (66%) sont nes a la Reunion, 79 (25%) sont non-fumeurs et 109 sont des femmes (35%). Parmi eux, 21% presentent une mutation activatrice EGFR. 23% des adenocarcinomes, 40% des femmes, 55% des non-fumeurs et 23% des patients nes a la Reunion sont mutes EGFR. Conclusion : La population diagnostiquee a la Reunion presente un fort taux de mutations EGFR. Ce dernier se rapproche des populations indiennes ce qui est probablement en lien avec les migrations et le metissage reunionnais. Ces resultats suggerent qu’il existe des interactions complexes entre la genetique et la part environnementale impliquees dans la carcinogenese du CBNPC.

Background Under-aged migrants (UAMs) may see their legal minority unrecognised by the French state. If they confront this decision at court, they stand in a legal void. They can benefit from a direct access to State Medical Aid and are not submitted to a minimum period of 3 months of staying in France unlike adults. Moreover, when accessing care, unrecognised UAMs are in an unclear situation as they are minors without legal representation. This research is based on a newly created program ran by Doctors of the World (MDM) in Nantes, aiming to enhance UAMs access to health care and rights through peer-support. Peer-support is intended to develop the empowerment the UAM and help them to be able to be the authors of their life thus develop their own abilities (Le Grand, 2018). The role of empowerment in health access is established (Wallerstein, 2006). The research aims at identifying the obstacles and levers in the implementation of the program, the modifications it can cause in the program. Methods The research is based on 3 months ethnographical observations, 9 formal interviews with UAM, 5 with professionals, and informal interviews. Results We identify that volunteers share a different perception of what is empowerment. Some would leave quite a large autonomy to UAMs while others find it difficult to alter the organisation to give space to UAMs. Finally, self-help mainly develops abilities of those UAMs who were more resourceful. Conclusions The analysis shows that a successful program of empowerment rely on shared views of its meaning. Moreover it shows that empowerment may help mainly those resourceful thus exacerbate some inequalities in ressources. Key messages The notions of empowerment and peer-support need to be well understood by all. Empowerment, as a side effect first exacerbates some inequalities of resources among UAMs.

SummaryThe migration of immune cells is guided by specific chemical signals, such as chemokine gradients. Their trajectories can also be diverted by physical cues and obstacles imposed by the cellular environment, such as topography, rigidity, adhesion, or hydraulic resistance. On the example of hydraulic resistance, it was shown that neutrophil preferentially follow paths of least resistance, a phenomenon referred to as barotaxis. We here combined quantitative imaging and physical modeling to show that barotaxis results from a force imbalance at the scale of the cell, which is amplified by the acto-myosin intrinsic polarization capacity. Strikingly, we found that macropinocytosis specifically confers to immature dendritic cells a unique capacity to overcome this physical bias by facilitating external fluid transport across the cell, thereby enhancing their space exploration capacity in vivo and promoting their tissue-patrolling function. Conversely, mature dendritic cells, which down-regulate macropinocytosis, were found to be sensitive to hydraulic resistance. Theoretical modeling suggested that barotaxis, which helps them avoid dead-ends, may accelerate their migration to lymph nodes, where they initiate adaptive immune responses. We conclude that the physical properties of the microenvironment of moving cells can introduce biases in their migratory behaviors but that specific active mechanisms such as macropinocytosis have emerged to diminish the influence of these biases, allowing motile cells to reach their final destination and efficiently fulfill their functions.

Indexación: Scopus. Dendritic cell (DC) trafficking from peripheral tissues to lymph nodes (LNs) is a key step required to initiate T cell responses against pathogens as well as tumors. In this context, cellular membrane protrusions and the actin cytoskeleton are essential to guide DC migration towards chemotactic signals. Caveolin-1 (CAV1) is a scaffolding protein that modulates signaling pathways leading to remodeling of the actin cytoskeleton and enhanced migration of cancer cells. However, whether CAV1 is relevant for DC function and specifically for DC migration to LNs is unknown. Here, we show that CAV1 expression is upregulated in DCs upon LPS- and TNF-a-induced maturation. CAV1 deficiency did not affect differentiation, maturation, or the ability of DCs to activate CD8+ T cells in vitro. However, CAV1-deficient (CAV1-/-) DCs displayed reduced in vivo trafficking to draining LNs in control and inflammatory conditions. In vitro, CAV1-/- DCs showed reduced directional migration in CCL21 gradients in transwell assays without affecting migration velocity in confined microchannels or three-dimensional collagen matrices. In addition, CAV1-/- DCs displayed reduced activation of the small GTPase Rac1, a regulator of actin cytoskeletal remodeling, and lower numbers of F-actin-forming protrusions. Furthermore, mice adoptively transferred with peptide-pulsed CAV1-/- DCs showed reduced CD8+ T cell responses and antitumor protection. Our results suggest that CAV1 promotes the activation of Rac1 and the formation of membrane protrusions that favor DC chemotactic trafficking toward LNs where they can initiate cytotoxic T cell responses. https://www.frontiersin.org/articles/10.3389/fimmu.2017.01794/full

Quality control is an important factor for manufacturing companies looking to prosper in an era of globalization, market pressures, and technological advance. The functionality and product quality cannot be guaranteed without this important aspect. Manufactured parts have deviations from their nominal (CAD) shape caused by the manufacturing process. Thus, geometric inspection is a very important element in the quality control of mechanical parts. We have focused here on the profile inspection of non-rigid parts which are widely used in the aeronautic and automotive industries. Non-rigid parts can have different forms in a freestate condition compared with their nominal models due to residual stress and gravity loads. To solve this problem, dedicated inspection fixtures are generally used in industry to compensate for the displacement of such parts for simulating the use state in order to perform geometric inspections. These fixtures and the inspection process are expensive and time-consuming. Our aim is therefore to develop an inspection method which eliminates the need for specialized fixtures by acquiring a point cloud from the displaced part using a contactless measuring system such as optical scanning and comparing it with the CAD model for the identification of deviations. Using a non-rigid registration method and finite element analysis, we will numerically inspect the profile of a non-rigid part. To do so, a simulated displacement is performed using an improved definition of boundary conditions for simulating unfixed parts. In this paper, we will apply an improved method on two industrial non-rigid parts with free-form surfaces simulated with different types of displacement, defect, and measurement noise.

The herbicide residue from intensive agricultural activity provokes environmental disturbances and human health injuries. Among the enzymatic disruptor herbicides, mesotrione is able to inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD), which plays a key role in the carotenoid synthesis. Therefore, enzyme-based sensors are innovative options for monitoring herbicides used in agriculture. Compared to the standard sensors, biosensors have assorted advantages, such as practicality, quick response, low cost, and high sensitivity. A nanobiosensor was developed herein based on HPPD for mesotrione detection. Theoretically, the molecular docking and molecular dynamics simulation estimated the interacting regions of HPPD with mesotrione. Experimentally, the atomic force microscope tip functionalization with HPPD immobilized in self-assembled monolayers was confirmed by fluorescence microscopy and atomic force spectroscopy. The cross-linker N-(3-dimethylaminopropyl)- $\mathrm{N}^\prime $ -ethylcarbodiimide hydrochloride was responsible for properly preserving the enzyme on the tip. The nanobiosensor proposed here was successfully able to detect mesotrione molecules. Such effectiveness in the development of nanobiosensors promises reliable, precise, and low-cost techniques, which apply to a broad range of issues, from ecology to medicine.

Annona muricata L. also called soursop, graviola, guanabana and sapoty (French creole) is a fruit tree growing in tropical countries. The fruits, seeds, leaves and roots are used in traditional medicine. Potential anticancer effects encourage patients to consume this product as self medication. The object of the study was to determine the prevalence of use of graviola as an anticancer agent by patients treated for a lung cancer.Our survey took place in two thoracic oncology day cares units of the university hospital of Reunion. All the patients treated by chemotherapy and immunotherapy for lung cancer were asked the same questions in a face to face interview over a 6-month period.One hundred questionnaires were collected. Sixty seven patients consumed graviola. In 53.7%, graviola was consumed as an anticancer agent and 25 patients took it regularly. Most often graviola was ingested as an infusion of boiled leaves (69.5%). The supply was exclusively local.A quarter of patients treated by chemotherapy for a lung cancer in Reunion consume graviola regularly as self medication. The consequences of this intake, drug interactions and side effects are unknown and would be interesting to identify.

T cells can become activated in lymph nodes following a diverse set of interactions with antigen-presenting cells. These cellular contacts range from short and dynamic to stable and long-lasting interactions, termed kinapses and synapses, respectively. Here, we describe a methodology to generate naïve T cells expressing a fluorescent probe of interest through the generation of bone marrow chimeras and to image T cell dynamics using intravital two-photon microscopy. In these settings, the formation of kinapses and synapses can be triggered by the administration of low and high affinity peptides, respectively. Finally, 3D cell tracking can help classify distinct T cell behaviors. These approaches should offer new possibilities for dissecting the process of T cell activation in vivo.

T Cells can form very stable (synapses) or very transient and migratory (kinapses) contacts with antigen-presenting cells. Here, we describe how microchannels can be used to conveniently study the distinct dynamics of T cells during antigen recognition. Microchannels provide a controlled confined environment that promotes T cell migration and recapitulates kinapse and synapse behaviors when coated with appropriate pMHC molecules. We also depict the advantages of this in vitro approach for addressing mechanistic issues and for analysis.

The randomized phase III ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab + lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in relapsed/refractory multiple myeloma. ELd reduced the risk of disease progression/death by 30% versus Ld (hazard ratio [HR] 0·70). Median time from diagnosis was 3·5 years. We present extended 3-year follow-up data. Endpoints included progression-free survival (PFS), overall response rate (ORR) and interim overall survival (OS). Exploratory post-hoc analyses included impact of time from diagnosis and prior lines of therapy on PFS, and serum M-protein dynamic modelling. ORR was 79% (ELd) and 66% (Ld) (P = 0·0002). ELd reduced the risk of disease progression/death by 27% versus Ld (HR 0·73; P = 0·0014). Interim OS demonstrated a trend in favour of ELd (P = 0·0257); 1-, 2- and 3-year rates with ELd versus Ld were: 91% versus 83%, 73% versus 69% and 60% versus 53%. In patients with ≥ median time from diagnosis and one prior therapy, ELd resulted in a 53% reduction in the risk of progression/death versus Ld (HR 0·47). Serum M-protein dynamic modelling showed slower tumour regrowth with ELd. Adverse events were comparable between arms. ELd provided a durable and clinically relevant improvement in efficacy, with minimal incremental toxicity. © 2017 John Wiley & Sons Ltd

T Cells can form very stable (synapses) or very transient and migratory (kinapses) contacts with antigen-presenting cells. Here, we describe how microchannels can be used to conveniently study the distinct dynamics of T cells during antigen recognition. Microchannels provide a controlled confined environment that promotes T cell migration and recapitulates kinapse and synapse behaviors when coated with appropriate pMHC molecules. We also depict the advantages of this in vitro approach for addressing mechanistic issues and for analysis.

T cells can become activated in lymph nodes following a diverse set of interactions with antigen-presenting cells. These cellular contacts range from short and dynamic to stable and long-lasting interactions, termed kinapses and synapses, respectively. Here, we describe a methodology to generate naive T cells expressing a fluorescent probe of interest through the generation of bone marrow chimeras and to image T cell dynamics using intravital two-photon microscopy. In these settings, the formation of kinapses and synapses can be triggered by the administration of low and high affinity peptides, respectively. Finally, 3D cell tracking can help classify distinct T cell behaviors. These approaches should offer new possibilities for dissecting the process of T cell activation in vivo.