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International audience; Objectives: To assess the contribution of whole-body magnetic resonance imaging (WBMRI) and bone scintigraphy (BS) in addition to skeletal survey (SS) in detecting traumatic bone lesions and soft-tissue injuries in suspected child abuse.Methods: In this prospective, multicentre, diagnostic accuracy study, children less than 3 years of age with suspected physical abuse were recruited. Each child underwent SS, BS and WBMRI. A blinded first review was performed in consensus by five paediatric radiologists and three nuclear medicine physicians. A second review investigated discrepancies reported between the modalities using a consensus result of all modalities as the reference standard. We calculated the sensitivity, specificity and corresponding 95% confidence interval for each imaging modality (SS, WBMRI and BS) and for the combinations [SS + WBMRI] and [SS + BS].Results: One hundred seventy children were included of which sixty-four had at least one lesion. In total, 146 lesions were included. The sensitivity and specificity of each examination were, respectively, as follows: 88.4% [95% CI, 82.0-93.1] and 99.7% [95% CI, 99.5-99.8] for the SS, 69.9% [95% CI, 61.7-77.2] and 99.5% [95% CI, 99.2-99.7] for WBMRI and 54.8% [95% CI, 46.4-63.0] and 99.7% [95% CI, 99.5-99.9] for BS. Sensitivity and specificity were, respectively, 95.9% [95% CI, 91.3-98.5] and 99.2% [95% CI, 98.9-99.4] for the combination SS + WBMRI and 95.2% [95% CI, 90.4-98.1] and 99.4% [95% CI, 99.2-99.6] for the combination SS + BS, with no statistically significant difference between them.Conclusion: SS was the most sensitive independent imaging modality; however, the additional combination of either WBMRI or BS examinations offered an increased accuracy.Key points: • SS in suspected infant abuse was the most sensitive independent imaging modality in this study, especially for detecting metaphyseal and rib lesions, and remains essential for evaluation. • The combination of either SS + BS or SS + WBMRI provides greater accuracy in diagnosing occult and equivocal bone injuries in the difficult setting of child abuse. • WBMRI is a free-radiation technique that allows additional diagnosis of soft-tissue and visceral injuries.

This study was initiated and conducted by several laboratories, 3 of the main cosmetic ingredient suppliers and 4 brands of cosmetics in France. Its objective is to show the interest and robustness of coupling chemical and genetic analyses in the identification of plant species. In this study, the Lavandula genus was used.In this study, we used two analytical methods. Chemical analysis from UHPLC (ultra-high-performance liquid chromatography) and genetic analysis from barcoding with genetic markers.Eleven lavender species were selected (botanically authenticated) and analysed. The results show that three chemical compounds (coumaric acid hexoside, ferulic acid hexoside and rosmarinic acid) and three genetic markers (RbcL, trnH-psbA and ITS) are of interest for the differentiation of species of the genus lavandula.The results show that the combination of complementary analytical methods is a relevant system to prove the botanical identification of lavender species. This first study, carried out on a plant of interest for cosmetics, demonstrates the need for authentication using a tool combining genetic and chemical analysis as an advance over traditional investigation methods used alone, in terms of identification and authentication reliability.Cette étude a été lancée et menée par plusieurs laboratoires, trois des principaux fournisseurs d’ingrédients cosmétiques et quatre marques de cosmétiques en France. Son objectif est de montrer qu’associer les analyses chimiques et génétiques dans l’identification des espèces végétales présente un intérêt et est une approche solide. Dans cette étude, c’est le genre Lavandula qui a été utilisé. MÉTHODES: Dans cette étude, nous avons fait appel à deux méthodes analytiques. L’analyse chimique, à partir de la chromatographie en phase liquide à haute performance (ultra-high-performance liquid chromatography, UHPLC), et l’analyse génétique en procédant à un codage à barres avec des marqueurs génétiques. RÉSULTATS: Onze espèces de lavande ont été sélectionnées (authentifiées du point de vue botanique) et analysées. Les résultats montrent que trois composés chimiques (acide coumarique hexoside, acide ferulique hexoside et acide rosmarinique) et trois marqueurs génétiques (RbcL, trnH-psbA et ITS) présentent un intérêt pour la différenciation des espèces du genre lavandula.Les résultats montrent que la combinaison de méthodes analytiques complémentaires est un système pertinent pour prouver l’identification végétale des espèces de lavande. Cette première étude, réalisée sur une plante qui offre un intérêt pour les cosmétiques, démontre la nécessité de procéder à une authentification à l’aide d’un outil qui conjugue analyse génétique et chimique ; elle représente une avancée par rapport aux méthodes d’investigation traditionnelles utilisées seules, en termes d’identification et de fiabilité de l’authentification.

Background The COVID‐19 pandemic may induce post‐traumatic stress disorder (PTSD) symptoms among patients with cancer, who also face adaptations to their treatment. The authors assessed the occurrence of PTSD symptoms, investigated pandemic‐induced adjustments in medical oncology practice in patients with cancer, and explored risk factors for PTSD and the association between PTSD symptoms, insomnia, and quality of life (QoL). Methods This prospective French study was conducted in patients with solid/hematologic tumors who were receiving medical treatment in the day care departments of 2 cancer centers during the lockdown. Adjustments to medical oncology practice were collected from medical records. PTSD (measured using the Impact of Event Scale‐Revised), insomnia (measured using the Insomnia Severity Index), QoL (measured using the Functional Assessment of Cancer Therapy‐General instrument), and cognitive complaints (measured using the Functional Assessment of Cancer Therapy–Cognitive Function instrument) were collected through validated questionnaires. Results Clinical data and questionnaires were available for 734 and 576 patients, respectively. The median patient age was 64 years, and 69% of patients were women. Twenty‐one percent of patients had PTSD. Twenty‐seven percent (95% CI, 23%‐30%) had an adjustment in their medical oncology program, including adjournments (29%), treatment interruptions (16%), modified treatment plans (27%), or adapted monitoring (27%). Women and patients experiencing an adjustment in oncology practice had a higher odds of PTSD (odds ratio= 2.10 [95% CI, 1.07‐4.14] and 1.65 [95% CI, 1.03‐2.63]; P, Post‐traumatic stress disorder symptomatology occurred in 21% of patients with cancer during the first lockdown due to COVID‐19, was more frequent among women, and was associated with adjustment in medical oncology treatments. Caregivers should pay special attention to the psychological needs of patients with cancer to prevent or manage post‐traumatic stress disorder symptoms.

Summary Background Abnormal coronary pattern may complicate coronary transfer during arterial switch operation. Objective To evaluate the accuracy of echocardiography in assessing the anatomy of coronary arteries in neonates with transposition of the great arteries, and determine impact on outcomes. Methods We conducted a retrospective analysis of data in neonates with transposition of the great arteries. Preoperative echocardiographic coronary artery pattern and surgical intraoperative reports were compared. Mismatch between transthoracic echocardiography and surgical intraoperative reports and the impact on perioperative outcome were assessed. Coronary patterns were classified into four groups: type 1 (normal); type 2 (risk of coronary with intramural course); type 3 (coronary loop); and type 2 + 3. Results Overall, 108 neonates who underwent an arterial switch operation were included: 68 were classified as type 1; seven as type 2; 32 as type 3; and one as type 2 + 3. Overall, 10 adverse events occurred. Five patients died, three from coronary causes. Survival was 96% at 1 month. Transthoracic echocardiography and surgical intraoperative reports differed in 17.6% of cases. Mortality was 15.8% in case of inappropriate diagnosis and 2.2% for appropriate diagnosis (P = 0.01). Mortality in type 2 was 66.7% in case of discordance versus 0% when concordant. Multivariable analysis found that inappropriate preoperative transthoracic echocardiography diagnosis of coronary pattern was the only significant risk factor for mortality (P = 0.04). Conclusions Echocardiography can assess coronary artery anatomy in neonates with transposition of the great arteries. Intramural coronary course is often misdiagnosed. Preoperative misdiagnosis of coronary artery anomaly may impact perioperative mortality. However, this assessment will have to be confirmed by further larger studies.

Background: Several European countries face a shortage of general practitioners (GPs), in part due to GP attrition. Most studies of GP attrition have focussed on why GPs decide to leave. Yet understanding why GPs decide to remain may also elicit potential interventions to reduce attrition. Objectives: This study examined GP graduates’ career trajectories and underlying decisions to elucidate the factors influencing GP attrition. Methods: We conducted semi-structured interviews of early to mid-career general practice graduates having completed training in Belgian French-speaking universities between 1999 and 2013. We sampled participants from three categories: full-time GPs, part-time GPs, no longer working as GPs. We analysed each participant’s career trajectory and broke it down into major phases. We performed thematic analysis of the factors influencing participants’ trajectories. We compared and contrasted trajectories to develop a typology of career trajectories. Results: We identified six types of career trajectories: ‘stable’ (never considered leaving general practice), ‘reaffirmed’ (had considered leaving but made substantial changes whilst remaining), ‘reactional reorientations’ (had left to escape the challenges of general practice), ‘inspired reorientations’ (had left to pursue a different job), ‘reorientations out of loyalty’ (had never wanted to practice as GPs and had remained true to their original professional aspirations) and ‘mobiles’ (valued change and did not want to set-up practice). Conclusion: Reasons GPs leave the profession are multiple. The typology that emerged indicates that only some of the career trajectories would benefit from interventions to reduce attrition such as improving working conditions and providing psychological support for GPs., SCOPUS: ar.j, info:eu-repo/semantics/published

While pain remains a burden for many cancer patients, their active involvement in dealing with it through therapeutic patient education (TPE) has proved effective in overcoming hurdles to pain management. This article describes how a regional TPE programme devoted to cancer pain was set up, as well as the difficulties and opportunities encountered during its implementation. Ten nurse-doctor pairs from the chronic pain units of Lower Normandy, after being trained in TPE, designed and built the EFFADOL (Ensemble Faire Face A la DOuLeur [Cope together with pain]) programme. They collaboratively developed the pedagogical, evaluation and communication tools used in the programme. After the educational diagnosis step, patients are able to follow three sessions in order to acquire the following skills: (1) understanding the different types of pain, (2) understanding pain treatments and their adverse reactions and (3) optimally managing pain on a daily basis. Patients can ask a relative to join the sessions and can choose their preferred modality (individual and/or collective sessions). Programme implementation and the importance of communicating with oncologists and independent health professionals are discussed. The programme, which is available to patients close to home, meets their needs as previously assessed through a regional prospective survey. Difficulties to include patients and opportunities to address them are identified. The programme's limitations mainly concern its organization, structure and communication issues. The main challenge remains the overhaul of care practices and the role of the caregiver to allow patient autonomy.

This article examines a singular yet overlooked facet of the Indigenous reality evoked in film: the figure of the Native American athlete. The cinematic portrayal defined here as Sporting Indiannes...

Peter Yates’ Breaking Away (1979) is a riveting example of sport biopic. Indeed, Yates’ film focuses on the story of Dave Blase, a Hoosier who competed in the Little 500 cycling race during his tim...

According to Patrick Diquet and Christophe Meunier, sports have not only constituted a focal point of cinema’s interest but also contributed to its rich history and its evolution for more than a ce...

Three posture asymmetries and their connections were assessed by a statistical study as rigorous as possible on the subjects of a sample from a population considered as normal after negative criteria. The comparison of probabilities observed with random probabilities shows that there is less than one chance in a thousand to make an error by rejecting the hypothesis that the asymmetries of the orthostatic posture are random. The definition of the limits of these asymmetries thus fits in the search for the conditions of a clinical examination of the posture.

Traumatic brain injury (TBI) is a chronic pathology, inducing long-term deficits that remain understudied in pre-clinical studies. In this context, exploration, anxiety-like behavior, cognitive flexibility, and motor coordination were assessed until 5 and 10 months after an experimental TBI in the adult mouse, using two cohorts. In order to differentiate age, surgery, and remote gray and white matter lesions, three groups (unoperated, sham-operated, and TBI) were studied. TBI induced delayed motor coordination deficits at the pole test, 4.5 months after injury, that could be explained by gray and white matter damages in ipsilateral nigrostriatal structures (striatum, internal capsule) that were spreading to new structures between cohorts, at 5 versus 10 months after the injury. Further, TBI induced an enhanced exploratory behavior during stressful situations (active phase during actimetry test, object exploration in an open field), risk-taking behaviors in the elevated plus maze 5 months after injury, and a cognitive inflexibility in the Barnes maze that persisted until 9 months after the injury. These behavioral modifications could be related to the white and gray matter lesions observed in ipsi- and contralateral limbic structures (amygdala, hilus/cornu ammonis 4, hypothalamus, external capsule, corpus callosum, and cingular cortex) that were spreading to new structures between cohorts, at 5 months versus 10 months after the injury. The present study corroborates clinical findings on TBI and provides a relevant rodent chronic model which could help in validating pharmacological strategies against the chronic consequences of TBI.

Resume Introduction Le traitement dans le cancer de l’ovaire localement avance est une chirurgie optimale suivie d’une chimiotherapie. Les patientes avec une dissemination tumorale importante, un OMS superieur a deux et un âge superieur a 75 ans sont de mauvaises candidates pour une chirurgie premiere agressive. La chirurgie d’intervalle, apres une chimiotherapie neo adjuvante, a pour but d’obtenir davantage de chirurgies completes, d’augmenter la survie et de diminuer la morbidite liee a la chirurgie. Le critere principal de jugement etait la survie sans progression. Les criteres secondaires de jugement etaient la survie globale et la morbi-mortalite post-chirurgie. Methode Il s’agit d’une etude retrospective effectuee dans deux centres de reference francais entre janvier 2000 et decembre 2015. Les patientes qui ne pouvaient pas beneficier d’une chirurgie initiale complete etaient operees apres trois cures de chimiotherapie au centre Francois Baclesse et apres au moins cinq cures au centre Rene Gauducheau. Resultats La population analysee comportait 104 patientes, 43 (41,0 %) patientes traitees au centre Rene Gauducheau (groupe 1) et 61 (59,0 %) patientes traitees au centre Francois Baclesse (groupe 2). La survie sans progression et globale etait similaire entre les deux groupes. Elles etaient respectivement de 15,9 mois et 34 mois dans le groupe 1 vs 15,4 mois et 37,6 mois dans le groupe 2 (p = 0,72 ; p = 0,65). La duree d’hospitalisation moyenne et la morbidite postoperatoire etait similaire dans les deux groupes. Conclusion Pour des patientes fragiles, afin de limiter une chirurgie invasive, faire plus de cinq cures de chimiotherapie peut etre une option raisonnable.

In recent years, government officials in Hungary, Poland and Austria have contested the authority of the EU in areas linked to core state powers, such as democracy and the rule of law and migrations. Analyzing the discursive strategies displayed by conservative and/or right-wing governments in these countries, the article shows how the old conflict line over sovereignty that has traditionally shaped the integration process–supranational vs domestic sovereignty–is being complemented by a new discourse which consists in disparaging EU ‘interference’ in the very name of European values and a common European identity, defined in opposition to multiculturalism and political liberalism. Pioneered by Viktor Orban, this discourse has been circulating among other Central European heads of government and incumbent parties’ officials in the wake of the refugee ‘crisis’, which opened up a discursive opportunity structure for its diffusion., SCOPUS: ar.j, info:eu-repo/semantics/published

IntroductionMindfulness meditation is likely to promote better management of stress, pain and negative emotions. We propose to address the benefit of meditation in an open setting associating people with cancer (target population), medical staff and witnesses (neither patient nor medical staff). This study aims (1) to evaluate the effects of meditation on wellness improvement and (2) to identify criteria and modalities for a subsequent randomised study.Methods and analysisWe propose a longitudinal pilot study consisting of a non-randomised experimental preintervention/postintervention survey. The intervention consists in delivering a meditation programme (12 weekly meditation sessions of 1.5 hours each), specifically adapted to our target population and addressing our research hypothesis in an open setting involving people with cancer, medical staff and witnesses (equally distributed in two groups of 15 participants). The main objective is to evaluate participants’ adherence to the programme. The effects of meditation will be evaluated on stress, quality of life, feeling of personal effectiveness, on the development of mindfulness and empathy, and on satisfaction and perception of a change in quality of life. We will also measure the putative added value of ‘meditating together’. This study is expected to allow validating the evaluation tools and refining the modalities of the workshops. We expect to demonstrate the evolution that this meditation-based intervention induces in the participants. We aim to promote bridge-building, between patients, medical staff but also others. In this way, one’s own suffering may be understood in the light of others’ suffering, thereby promoting the sense of otherness and giving insights into ‘living better with’. This exploratory study will investigate the relevance of this hypothesis, which could then be explored by a randomised study.Ethics and disseminationThe protocol was approved by the local ethics committee (Comité de Protection des Personnes Est II). Trial findings will be published in peer-reviewed journals.Trial registration numberNCT04410185.

International audience; Human activities induce changes on land use and land cover. These changes are most significant in urban areas where topographic features (e.g., building, road) affect the density of impervious surface areas and introduce a range of urban morphological patterns. Those characteristics impact the energy balance and modify the climate locally (e.g., inducing the so-called Urban Heat Island phenomenon).Therefore, there is a need for georeferenced morphological indicators as well as urban classifications (such as Local Climate Zones) that can be directly used for planning or as inputs of climate models. GeoClimate is dedicated to this purpose: it converts raw geographical data (OpenStreetMap and French BDTopo) into indicators useful for climate applications (sky view factor, vegetation fraction, etc.) However, its application is not limited to the climate field.The indicators calculated in GeoClimate can also be used for other diagnostic or planning purposes: studying the territory fragmentation, the influence of the urban fabric on pollution (noise or air chemical transport), the energy consumption, etc. GeoClimate is available as free and open source geospatial software.

BackgroundCervical cancer is the tenth diagnosed cancer in the world. Early-stage and locally recurrent disease may be cured with radical surgery or chemo-radiotherapy. However, if disease persists or recurs, options are limited and the prognosis is poor. In addition to chemotherapy, bevacizumab, an antiangiogenic agent, has recently demonstrated its efficacy in this setting. Cabozantinib is an oral small molecule tyrosine kinase inhibitor that exhibits potent inhibitory activity against several receptor tyrosine kinases that are known to influence tumor growth, metastasis, and angiogenesis. The main targets of Cabozantinib are VEGFR2, MET and AXL. It is currently approved for the treatment of metastatic renal cell carcinoma, hepatocellular carcinoma and medullary thyroid carcinoma. Given its angiogenic properties associated with growth factor receptors inhibition, Cabozantinib represents a potential active treatment in cervical carcinoma. In this context, we propose to assess the efficacy and safety of cabozantinib monotherapy in advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment.MethodsThis study is a single-arm two-stage multicenter phase II aiming to simultaneously assess efficacy and safety of Cabozantinib among advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment. The main criterion will be based on both safety and clinical efficacy by conducting a Bryant-and-Day design. Safety endpoint is the proportion of patients with clinical gastro-intestinal (GI) perforation/fistula, GI-vaginal fistula and genito-urinary (GU) fistula events grade ≥ 2 (NCI CTCAE V.5.0) occurring up to one month after the end of treatment. Efficacy endpoint is the proportion of patients with disease control rate 3 months after Cabozantinib initiation. A patients’ self-reported quality of life evaluation is also planned, as well as the investigation of nutritional outcomes. Cabozantinib will be administered at the daily dose of 60 mg given orally, without interruption until disease progression or discontinuation for any cause.DiscussionCabozantinib is a promising drug for patients with advanced/metastatic cervical cancer where few therapeutics options are available after failure to platinum-based regimen metastatic CC. It appears challenging to assess the interest of Cabozantinib in this indication, taking into account the potential toxicity of the drug.Trial registrationNCT04205799, registered “2019 12 19”.Protocol versionVersion 3.1 dated from 2020 08 31.

Evaluating the aerosolization of droplets from surgical instruments to assess the implications of surgery in SARS-CoV-2 transmission for both patients and providers. Cadaver study. Outpatient surgery center. Aerosolized particles between 0.3 and 25 microns were measured. Instruments tested included monopolar cautery with and without suction, bipolar cautery, a bipolar vessel sealing device, and tissue scissors. Each trial was compared to a background reading. Monopolar cautery without suction, Ligasure used continuously and Bipolar cautery produced the most aerosols. Monopolar cautery with simultaneous suction produced no detectable aerosols. Ligasure used for a single cycle produced notably fewer aerosols than during continuous use. Most aerosols produced were

General practitioners (GPs) are first-line clinicians in melanoma diagnosis. It is, therefore, important to ensure that they maintain their melanoma diagnostic accuracy over time. The objective of this study was to assess the short- and long-term competences of GPs after a training session in naked-eye melanoma diagnosis. An interventional prospective study was conducted whereby, over a 6-month period, GPs attended a 1-h melanoma diagnostic training session. To assess their acquired competences, GPs were asked to fill in a questionnaire on basic melanoma knowledge and to evaluate 10 clinical images of pigmented skin lesions prior to training, immediately after and 1 year later. In total, 89 GPs completed the questionnaire prior and immediately after training. As expected, the number of GPs who appropriately managed \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge$$\end{document}≥ 50% of the melanoma cases increased after training (P

To prevent the thermally induced spatial beam degradation occurring in high-power fiber lasers and amplifiers, index-depressed core “fully aperiodic large-pitch fibers” (FA-LPFs) have been designed and fabricated. In contrast to previous experimental works performed on FA-LPFs, in which the active core and the surrounding cladding material are quasi-index-matched, the core refractive index is in slight depression compared to the surrounding material ( Δ n ≈ − 3 × 10 − 5 ). Thus, the index-depressed fiber core tends first to behave as an anti-guide, preventing light from being properly guided into it. However, by increasing the absorbed pump power, the thermal load induces a parabolic refractive index change sufficient to compensate for the − 3 × 10 − 5 index depression in the core, enabling a robust single-mode amplification at high average power. As a proof of concept, using a 110 µm depressed core FA-LPF, M 2 values of 1.3 were demonstrated in amplifier configuration from 60 W to a maximal value of 170 W of emitted average power only limited by the available pump power.

International audience; BACKGROUND. High circulating levels of ceramides (Cer) and sphingomyelins (SM) have been associated with cardiometabolic diseases. The consumption of whole-fat dairy products, which naturally contain such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown. We investigated how milk PL supplementation impacts circulating and intestinal SM and Cer composition in association with improvement of cardiovascular markers.METHODS. In a 4 week-randomized double-blind controlled study, 58 postmenopausal women consumed daily a cream cheese containing 0, 3 or 5 g of milk PL. Postprandial metabolic explorations were performed before and after the supplementation. SM and Cer species were analyzed in serum, intestine-derived chylomicrons and feces. The ileal content of 4 ileostomy patients was also explored after milk PL intake in a crossover double-blind study.RESULTS. Milk PL consumption decreased serum atherogenic C24:1 Cer (Pgroup = 0.033), C16:1 (Pgroup = 0.007) and C18:1 (Pgroup = 0.003) SM species. Changes in serum C16+18 SM species were positively correlated with the reduction of total cholesterol (r = 0.706, P < 0.001), LDL-C (r = 0.666, P < 0.001) and ApoB (r = 0.705, P < 0.001). Milk PL decreased the concentration in chylomicrons of total SM (Pgroup < 0.0001) and of C24:1 Cer (Pgroup = 0.001). Saturated SM and Cer species, which are also the major species found in milk PL-enriched cheeses, increased in ileal efflux and feces. There was a marked increase in total fecal Cer after milk PL supplementation (Pgroup = 0.0002). Milk PL also modulated the abundance of some specific SM and Cer species in ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSION. These data demonstrate that milk PL supplementation decreases atherogenic SM and Cer species associated with an improvement of cardiovascular risk markers. Our findings bring new insights on sphingolipid metabolism in the gastrointestinal tract, especially Cer as such signaling molecules potentially participating in the beneficial effect of milk PL. ClinicalTrials.gov, NCT02099032, NCT02146339.

OBJECTIVE To determine whether ileocaecal endometriosis (ICE) is a marker for low rectal endometriosis (LRE) severity. DESIGN Retrospective cohort study. SETTING France. POPULATION AND SAMPLE Analysis of 375 colorectal resections performed in women undergoing complete surgery for LRE from January 1995 to December 2015 in a university centre for endometriosis. METHODS Univariate and multivariate analysis of anatomical, postoperative clinical, and long-term outcomes according to presence of ICE. MAIN OUTCOMES AND MEASURES Mean number and type of deep infiltrating endometriosis (DIE) lesions, the existence of an associated endometrioma, and mean total American Society for Reproductive Medicine (ASRM) score. RESULTS The prevalence of ICE was 25.6%. Primary end-point data showed that women with ICE had a significantly higher adjusted number of DIE lesions (OR = 1.43, 95% CI 1.02-3.03; P = 0.048), higher prevalence of endometriomas (OR = 1.91, 95% CI 1.04-3.51; P = 0.044), more associated DIE sigmoid lesions (OR = 2.12, 95% CI 1.07-3.91; P = 0.025), and a higher mean total ASRM score (OR = 2.07, 95% CI 1.12-4.14; P = 0.025). Women with ICE resected during the surgical procedure for LRE did not have more adverse postoperative clinical outcomes than ICE-negative patients. CONCLUSION Ileocaecal endometriosis was significantly associated with greater LRE severity. In a complete surgical resection strategy, combining resection of ICE and LRE did not appear to increase postoperative rates of complications, morbidity or recurrence, nor did it seem to impair long-term clinical outcomes. TWEETABLE ABSTRACT In women with low rectal endometriosis, 25% have an associated ileocaecal location that is a marker for severity.

Ineffective esophageal motility is the most frequent esophageal motility disorder. It is currently defined by 50% or more ineffective esophageal contractions and a normal lower esophageal sphincter relaxation on high-resolution esophageal manometry. Although reported in patients without symptoms, it is typically associated with gastro-esophageal reflux disease, and might be a consequence of the reflux. Ineffective esophageal motility can account for a certain degree of dysphagia, and is associated with a more severe gastroesophageal reflux. Todate, no specific endoscopic or pharmacologic treatment is available, and proton pump inhibitor are advisable when gastro-esophageal reflux is associated.

Purpose: Patient education constitutes a relevant strategy to improve pain management. In the field of therapeutic patient education (TPE), we aimed 1) to assess pain impact in cancer patients, 2) to identify patients' educative needs in pain management, and 3) to refine research criteria for its future evaluation. Patients and methods: Pain intensity, relief and interference were assessed in 75 cancer patients with unbalanced background pain. Self-assessment questionnaire evaluated i) patients' pain management and ii) their knowledge and needs in TPE. Results: Most patients experienced pain for more than 6 months and 41.6% reported adequate pain relief. Understanding pain and pain management were major patients' preferences (>58%). Most patients declared they knew their pain treatments, but fewer than half of them were able to name them. However, education concerning pain treatment was considered as essential in

International audience; BACKGROUND:Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM.METHODS:The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa.DISCUSSION:Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer.TRIAL REGISTRATION:NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.

In recent years, the software applications for medical assistance, including the telerehabilitation, have known a high and a continuous presence in the medical area. ePHoRt is a Web-Based Platform for the remote home monitoring rehabilitation exercises in patients after hip replacement surgery. It involves a learning phase and a serious game scheme for the execution and the evaluation of the exercises as part of a therapeutic program. A modular software architecture is proposed, under the patient perspective, to be used as a reference model for researchers or professionals who wish to carry out tele-rehabilitation platforms, and to guarantee security, flexibility and scalability. The architecture incorporates two main components. The first one manages the patient’ therapeutic programs taking into account two principles: (1) maintain loose coupling between the layers of the framework and (2) the Don’t Repeat Yourself (DRY). The second one evaluates the performed exercises in real time considering an independent acquisition mechanism for the patient movements and two artificial algorithms. The first algorithm allows evaluating the quality of the movements, while the second one allows assessing the levels of pain intensity by recognizing the patient’ emotions when performing the movements. Details of the components and the meta-model of the architecture are presented and discussed considering their advantages and disadvantages.

La Presse Medicale - In Press.Proof corrected by the author Available online since jeudi 25 octobre 2018

Background Patients with schizophrenia (SZ) present a higher level of cardiovascular morbidity than the general population due to poor physical fitness and a sedentary lifestyle. Moreover, despite major therapeutic advances in the management of SZ, some clinical symptoms remain resistant to pharmacological approaches. A large number of studies support the effectiveness of physical activity (PA) for both physical and mental health in SZ. The main objective of the present study is to assess the effects of a remote, web-based adapted PA program (e-APA) compared to a health education program (e-HE) on brain plasticity in SZ and healthy volunteers (HV). The secondary objectives are to assess the effects of e-APA on other cerebral variables as well as clinical, neurocognitive, circadian, biological, and physiological variables. Methods: The study is an interventional, multicenter, randomized open-label controlled trial. Forty-two SZ will be randomized to either the active group (e-APA, N = 21) or non-active group (e-HE, N = 21), and 42 HV will be matched to SZ according to age, gender, and level of PA. Interventions will consist of 32 sessions (2x60 minutes/week, for 16 weeks) via supervised home-based videoconferencing. The active group will carry out an individualized PA program of moderate to vigorous intensity. Pre- and post-intervention cerebral magnetic resonance imaging (MRI) will be performed to evaluate changes in global hippocampal volume. Other cerebral assessments using diffusion tensor imaging, arterial spin labelling, spectroscopy and resting-state functional MRI will be performed. In addition, clinical, neurocognitive and circadian rhythms assessments as well as physical tests and biological analyses will be conducted. Discussion: To our knowledge, this is the first study aiming to evaluate the efficacy of APA delivered by supervised home-based videoconferencing in SZ. Moreover, using multimodal MRI, this study could clarify the pathophysiological mechanisms underlying the efficacy of APA. Finally, this innovative approach (remote, web-based APA) might also increase participation in long-term PA since PA-based programs are known to have low adherence and early dropout. The results of this study should promote the inclusion of PA interventions as a novel adjunctive therapy for SZ. Trial registration: ClinicalTrials.gov identifier: NCT03261817. Registered on 16 August 2017.

National audience; Median follow-up is often used to assess the quality of follow-up in longitudinal studies. Its relevance to evaluate the quality of the produced estimations seems obvious. However, there is no clear decision rule on its use. We evaluated the quality of the Kaplan-Meier estimator of the survival rate according to different values of the median follow-up in order to propose an objective decision rule.We performed a sensitivity analysis via Monte Carlo simulations based on a reference sample, according to the literature. The log(–log) confidence interval of the Kaplan-Meier estimator of survival rate was evaluated in terms of coverage probability and length. The Monte Carlo simulation was performed for 10,000 replications considering 170 values for the median follow-up.We could observe a high relationship between the quality of the estimation and the median follow-up. Heavy censorship leads to an overestimation of the survival rate and anti-conservative confidence intervals. From a threshold value of the median follow-up, the values of the criteria reach a plateau and good estimations of the survival rate are achieved.More precisely, simulations show that reliable Kaplan-Meier estimations cannot be obtained when the median follow-up is less than two thirds of the estimation time. This provides factual elements to evaluate results for long longitudinal studies or to assess ongoing cohorts.

We are grateful to the Expert Committees (CESs) on "Health reference values" and on “Assessment of the physical and chemical risks in foods” for proofreading and validating this work. We are grateful to Camille Béchaux for the discussions on the PBPK model.; International audience; In France, part of the population is overexposed to cadmium by the diet.In our work, we first revised the tolerable daily intake (TDI) of 0.36 μg Cd.kg bw.d.-1 proposed by the European Food Safety Authority (EFSA), derived from effects on kidneys and based on the critical urinary Cd concentration of 1.0 μg Cd.g-1 creatinine for humans.After reviewing the epidemiological data on Cd toxicity published after 2011, bone effects were selected as the critical effects. Body burden data of 0.5 µg.g-1 creatinine was chosen for the critical threshold for human urinary cadmium concentrations.To be used for the derivation of the new oral toxicological reference value, we used a modified physiologically based pharmacokinetic model (PBPK). The reverse calculation on the PBPK model gave a TDI of 0.35 µg Cd.kg bw-1.day-1.This TDI is compatible with a urinary Cd concentrations not exceeding 0.5 µg Cd.g-1 creatinine, in a 60 year-old adult, assuming that ingestion is the only source of exposure to Cd at 60 years. After implementing the PBPK model with French physiological data, Cd biological reference values as a function of age were modelled so as to remain below the revised health-based guidance values.

International audience; Cadmium is a ubiquitous and highly toxic contaminant that can cause serious adverse effects.The European Food Safety Authority (EFSA) and the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) have shown that the risk related to food contamination by cadmium cannot be ruled out in Europe and France. Fertilizing material is one of the main sources of cadmium contamination in the food chain on which regulators can play to reduce cadmium exposure in the population. The aim of this work was to develop a mass-balance approach integrating the various environmental sources of cadmium to estimate the effects of a decrease in cadmium concentrations in crop fertilizers on dietary exposure and on the health risk. This approach led to a predictive model that can be used as a decision-making tool. Representative and protective fertilization scenarios associated with controlled cadmium levels in mineral phosphate fertilizers were simulated and converted into cadmium fluxes.Cadmium inputs from industrial mineral phosphate fertilizers were then compared with cadmium brought by the application of manure, sewage sludge and farm anaerobic digest, at the levels typical of French agricultural practices. Regardless of the fertilizer and scenario used, a flux lower than 2 g Cd.ha-1.year-1 reduces both the accumulation in soils and the transfer of cadmium in the food chain. It corresponds to a cadmium content of 20 mg.kg P2O5-1 or less in mineral phosphate fertilizers. Modelling the transfer of cadmium from the soil to consumed food made it possible to propose cadmium limits in fertilizers applied in France. In a global context of ecological transition to promote human health, this research will help risk managers and public authorities in the regulatory decision-making process for the reduction of environmental cadmium contamination and human exposure.

Local conductance behavior of various moiré lattices, moiré superstructures, and Kagome-like moiré are resolved down to sub–5 nm., Two-dimensional heterostructures composed of layers with slightly different lattice vectors exhibit new periodic structure known as moiré lattices, which, in turn, can support novel correlated and topological phenomena. Moreover, moiré superstructures can emerge from multiple misaligned moiré lattices or inhomogeneous strain distributions, offering additional degrees of freedom in tailoring electronic structure. High-resolution imaging of the moiré lattices and superstructures is critical for understanding the emerging physics. Here, we report the imaging of moiré lattices and superstructures in graphene-based samples under ambient conditions using an ultrahigh-resolution implementation of scanning microwave impedance microscopy. Although the probe tip has a gross radius of ~100 nm, spatial resolution better than 5 nm is achieved, which allows direct visualization of the structural details in moiré lattices and the composite super-moiré. We also demonstrate artificial synthesis of novel superstructures, including the Kagome moiré arising from the interplay between different layers.

Background/Objectives Physical activity (PA) has significant benefits for older adults. However, the recommended PA is rarely achieved in nursing homes. In this proof of concept study, we assessed whether virtual reality (VR) could help to increase spontaneous PA during a stationary cycling session. Design Prospective crossover proof of concept study. Setting Nursinghome. Participants Twelve participants (10 men) aged 63–88, able-bodied but with moderate cognitive impairment. Intervention TWO stationary cycling sessions with and withoutVR. Measurements Cycling distance, pedalling duration, average speed, mean pedalling cadence and the modified Borg rating of perceived exertion scale. Results Cycling distance and duration were significantly higher in the VR condition. Most participants would rather repeat cycling sessions with VR than without. Conclusion The use of VR seems feasible to help achieve PA recommendations for able-bodied people living in nursing homes, even with moderate cognitive impairments.

In order to design efficient electric motors for automotive applications, it is necessary to consider the constraints from different physics: size, weight, torque density, temperature, and mechanical stress due to high speed and vibration limits. A new methodology taking into account all these aspects will be presented in this paper. A design of experiments (DOE) analysis is carried out in order to build a surface of response and then optimize the motor, fulfilling the different constraints by only modifying the rotor shape.

Aims Treatment decisions in patients with scimitar syndrome (SS) are often challenging, especially in patients with isolated SS who are often asymptomatic and who might be diagnosed accidentally. We queried a large multi-institutional registry of SS patients to evaluate the natural history of this condition and to determine the efficacy of surgical treatment in terms of survival and clinical status. Methods and results We collected data on 485 SS patients from 51 institutions; 279 (57%) patients were treated surgically (STPs) and 206 (43%) were clinically monitored (CMPs). Median age at last follow-up was 11.6 years (interquartile range 4-22 years). Overall survival probability at 30 years of age was 88% [85-92% confidence intervals (CI)] and was lower in patients with associated congenital heart disease (CHD) (P

Background: Endoscopic resection of extensive esophageal neoplastic lesions is associated with a high rate of esophageal stricture. Most studies have focused on the risk factors for post-endoscopic esophageal stricture, but data on the therapeutic management of these strictures are scarce. Our aim is to describe the management of esophageal strictures following endoscopic resection for early esophageal neoplasia. Methods: We included all patients with an endoscopic resection for early esophageal neoplasia followed by endoscopic dilatation at a tertiary referral center. We recorded the demographic, endoscopic, and histological characteristics, and the outcomes of the treatment of the strictures. Results: Between January 2010 and December 2019, we performed 166 endoscopic mucosal resections and 261 endoscopic submucosal dissections for early esophageal neoplasia, and 34 (8.0%) patients developed an esophageal stricture requiring endoscopic treatment. The indication for endoscopic resection was Barrett’s neoplasia in 15/34 (44.1%) cases and squamous cell neoplasia (SCN) in 19/34 (55.9%) cases. The median [(interquartile range) (IQR)] number of endoscopic dilatations was 2.5 (2.0–4.0). Nine of 34 (26.5%) patients required only one dilatation, and 22/34 (65%) had complete dysphagia relief following three endoscopic treatment sessions. The median number of dilatations was significantly higher for SCN [3.0 (2–7); range 1–17; p = 0.02], and in the case of circumferential resection [4.0 (3.0–7.0); p = 0.03]. Endoscopic dilatation allowed a sustained dysphagia relief in 33/34 (97.0%) patients after a mean follow-up of 25.3 ± 22 months. Conclusion: Refractory post-endoscopic esophageal stricture is a rare event. After a median of 2.5 endoscopic dilatations, 97.0% of patients were permanently relieved of dysphagia. Circumferential endoscopic esophageal resections should be considered when indicated.

Background: Treated cancer patients (pts) are at high risk to develop severe COVID-19 evolution and guidelines proposed some preventive medical oncologic treatments (tt) adjustments Pts had to face with this unprecedented situation, as caregivers forced to suddenly adjust their practices We assessed the pandemic-induced therapeutic modifications of pts cancer tt and the psychological impact on pts and caregivers Methods: This prospective French study was initiated among pts with solid/hematologic malignancy receiving a medical tt during the lockdown in outpatient departments of 2 cancer centers Tt modifications were collected from medical records Perceived and post-traumatic stress (PSS, IES-R), sleep (ISI), quality of life QoL (Fact-G) and cognitive complaint (Fact-Cog) were reported at baseline (during the lockdown) and will be collected at 3 and 6 months PSS and professional burnout/self-efficacy (MBI, GSES) were also reported by caregivers Results: Baseline clinical data are available for 621 pts and questionnaires for 575 pts (93%) and 73 caregivers Pts and caregivers median ages were 64 [24-89] and 40 [22-63], 69% and 81% women Caregivers were mainly nurses (48%) and oncologists (30%) 98% of pts had solid tumors, 59% with metastatic disease and 47% de novo treated Main tts included chemotherapy (72%), immunotherapy (31%) and targeted therapy (13%), 37% starting during the lockdown 27% of pts had tt modifications including 30% adapted monitoring (mainly phone-consultation), 15% tt interruptions, 32% postponed tt, 19% administration rhythm modifications, more frequently among lung cancer, tt initiated before lockdown, immunotherapy and targeted therapy Severe perceived stress, post-traumatic stress and insomnia were observed in 6%, 21% and 24% of pts More pts with tt modifications presented severe post-traumatic stress (27% vs 19%, p=0 05) Tt modifications did not impact on QoL/cognition Perceived stress score was higher among caregivers than pts (p=0 035) but 2/3 reported professional accomplishment and self efficacy Conclusions: Lockdown due to COVID-19 induced tt modification in 1/4 of pts with a majored post-traumatic stress Despite a high level of stress, caregivers coped with the situation Clinical trial identification: NCT04366154, registered on 2020, April, 16th Legal entity responsible for the study: Comprehensive Cancer Centre Francois Baclesse, Caen France Funding: French Fondation ARC (Cancer Research Association) Disclosure: All authors have declared no conflicts of interest

Vibratory characterization of electrical machines is an important task that should be performed early in the design stages. Treat it as an afterthought may lead to high vibration and noise levels incompatible with the application requirements.In this paper, multiphysics FEM simulation is used to model a PMSM (Permanent Magnet Synchronous Machine) from both, the magnetic and vibratory point of view.A 2D magnetic simulation is carried out to get the excitation forces over the stator. In parallel, a 3D modal simulation will reproduce an Experimental Modal Analysis (EMA), identifying machine’s vibration modes. Finally, the Maxwell forces obtained by the magnetic simulation will be used as input to run an Operation Modal Analysis (OMA) which output is the vibration levels in the machine’s housing.Magnetic, EMA and OMA simulations has been validated through prototype testing. A detailed comparison between simulation results and experiments is presented.

Purpose The aim of this prospective study (ClinicalTrials.gov: NCT01880203) was to evaluate the diagnostic and prognostic value of a 7-panel mutation testing in the aspirates of thyroid nodules with indeterminate cytology (IC). Methods Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda III–V) for which surgery had been recommended. Detection of BRAF and RAS mutations was performed using pyrosequencing and RET/PTC and PAX8/PPARγ rearrangements using Real-Time quantitative reverse transcription‐polymerase chain reaction (RT-PCR). Results Among 131 nodules with IC, 21 (16%) were malignant including 20 differentiated cancers and one thyroid lymphoma. Molecular abnormalities were identified in 15 nodules with IC corresponding to 10 malignant and 5 benign tumours. BRAF mutation was detected in 4 nodules all corresponding to classic PTC, and PAX8/PPARγ rearrangement in 2 HCC. In contrast, RAS mutation was identified in eight nodules, of which four were malignant, and one RET/PTC3 rearrangement in a follicular adenoma. This data resulted in an accuracy of 88%, sensitivity of 48%, specificity of 95%, positive-predictive value of 67%, and negative-predictive value of 91%. After a 56 month’s follow-up, the proportion of excellent response was similar in patients with molecular alterations (67%) and those without (60%). Conclusions By increasing the overall risk of cancer from 16 to 67% in mutated nodules and by diminishing it to 9% in wild-type, this study confirms the relevance of the 7-panel mutation testing in the diagnostic of nodules with IC. Genetic testing, however, did not predict outcome in the cancer patient subgroup.

BACKGROUND: General practitioners (GPs) are among the main actors involved in early melanoma diagnosis. However, melanoma diagnostic accuracy and management are reported to be insufficient among GPs in Europe. OBJECTIVES: The primary aim of this observational prospective study was to shed light on melanoma diagnostic practices among French-speaking Belgian GPs. The second aim was to specifically analyse these GPs’ pigmented skin lesion diagnostic accuracy and management. METHODS: GPs from the five French-speaking districts of Belgium were asked to complete a questionnaire, before taking part in a melanoma diagnostic training session. First, we assessed the GPs’ current melanoma diagnostic practices. Then, their pigmented skin lesion diagnostic accuracy and management were evaluated, through basic theoretical questions and clinical images. These results were subsequently analysed, according to the GPs’ socio-demographic characteristics and medical practice type. RESULTS: In total, 89 GPs completed the questionnaire. Almost half of the GPs (43%; CI=33;54) were confronted with a suspicious skin lesion as the main reason for consultation once every three months, while 33% (CI=24;43) were consulted for a suspicious lesion as a secondary reason once a month. Prior to training, one-third of the GPs exhibited suboptimal diagnostic accuracy in at least one of six “life-threatening” clinical cases among two sets of 10 clinical images of pigmented skin lesions, which can lead to inadequate patient management (i.e., incorrect treatment and/or inappropriate reinsurance). Conclusion: This study underlines the need to train GPs in melanoma diagnosis. GPs’ pigmented skin lesion diagnostic accuracy and management should be improved to increase early melanoma detection.

Fiber lasers are a great source for tunable lasers due to the wide and relatively flat gain spectra of rare earth transitions in a glassy host (as compared to crystals). Thulium (Tm)-doped fibers, in particular, offer an extremely wide tunability of up to 330 nm in the 2μm wavelength region in a dual gain module configuration1. More recently, new concepts have emerged, which allow the synchronized emission of two or even more wavelengths2. These sources are particularly useful for nonlinear frequency conversion via four-wave mixing (FWM) or difference frequency generation (DFG). We will present a very versatile fiber-integrated approach based on Fiber-Bragg-Grating (FBG) arrays implemented in a theta-shaped cavity. The Tm-doped fiber source emits typical average powers of 0.5W and is tunable from 1931nm to 2040nm. The emission linewidth follows the spectral characteristic of the FBG and is typically 30GHz in our case. This concept allows a constant wavelength-independent repetition rate as well as a synchronous emission of two or even three independently tunable wavelengths. The tuning is performed purely electronically by optical gating, and in addition the pulse duration can be tuned between 4ns and 25ns. The switching speed is very fast and was measured to be less than 10μs. These experiments will be contrasted with a different approach based on a VLMA fiber associated to a set of two volume Bragg gratings (VBG), one of them being angle-tunable. This concept allows pulsed (Q-switched) as well as CW operation and features a continuous and wider tunability of up to 144nm especially and also the dual wavelength mode. The output power was > 4.5W in CW mode and pulse peak power of 12kW have been obtained in the Q-switched mode with pulse durations of 25ns.

International audience; The present study evaluated the exposure of children aged from one to 36 months to seven groups of mycotoxins, in the context of the infant French Total Diet Study (iTDS). Exposure was then compared to the health-based guidance values (HBGVs) for each mycotoxin. The value of the 90th percentile of exposure to nivalenol, patulin, fumonisins and zearalenone was less than 40% of the HBGV considered relevant for children. On the other hand, a risk could not be excluded for ochratoxin A and aflatoxins as exposure was close to the HBGV for ochratoxin A and the margin of exposure was much lower than the critical margin of 10,000 for aflatoxins. The HBGVs for toxins T2 and HT2, and for deoxynivalenol (DON) and its acetylated compounds were exceeded. Five percent to 10% of the children aged 5–12 months exceeded the HBGV considering the lower bound hypothesis for toxins T2 and HT2 and 7.5%–27% of the children aged 5 months and above exceeded the HBGV for DON. Consequently, the exposure of young children raises safety concerns for T2/HT2 and DON. Efforts should therefore be pursued to decrease their exposure to these molecules.

Despite the progresses performed in the field of radiotherapy, toxicity to the healthy tissues remains a major limiting factor. The aim of this work was to highlight blood biomarkers whose variations could predict the occurrence of late cutaneous side effects. Two groups of nine patients treated for Merkel Cell Carcinoma (MCC) were established according to the grade of late skin toxicity after adjuvant irradiation for MCC: grade 0, 1 or 2 and grade 3 or 4 of RTOG (Radiation Therapy Oncology Group)/EORTC (European Organization for Research and Treatment of Cancer). To try to discriminate these 2 groups, biomarkers of interest were measured on the different blood compartments after ex vivo irradiation. In lymphocytes, cell cycle, apoptosis and genotoxicity were studied. Oxidative stress was evaluated by the determination of the erythrocyte antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, reduced and oxidized glutathione) as well as degradation products (protein carbonylation, lipid peroxidation). Inflammation was assessed in the plasma by the measurement of 14 cytokines. The most radiosensitive patients presented a decrease in apoptosis, micronucleus frequency, antioxidant enzyme activities, glutathione and carbonyls, and an increase in TNF-a (Tumor Necrosis Factor a), IL-8 (Interleukin 8) and TGF-&beta, 1 (Transforming Growth Factor &beta, 1) levels. These findings have to be confirmed on a higher number of patients and before radiotherapy and could allow to predict the occurrence of late skin side effects after radiotherapy.

International audience; High power diffraction-limited 1064 nm fiber lasers operating in the nanosecond regime can be used for long-range LIDAR and micromachining applications. Peak power is limited by non-linearities, there is therefore an interest to develop fibers exhibiting a very large mode field effective area. New fibers are being developed in the frame of the 4F consortium ("French laser Fibers for Factories of the Future") to fulfill this need. We report on results obtained with a new 39 µm core diameter polarization maintaining ytterbium doped fiber that has been manufactured using the powder sintering technology. It features a large cladding absorption close to 20 dB/m at 976 nm (small signal) and a mode field diameter close to 32 µm. We built a pulsed MOPA. The preamplifier generates 2.5 ns pulses at 1064 nm with 8.5 W average power at 1 MHz pulse repetition frequency. The power amplifier is based on the 39 µm core fiber with 215/230µm hexagonal cladding counterpumped at 976 nm. It features 72 % slope efficiency delivering 72.2 W average power at a pulse repetition rate of 1 MHz. An end-cap was spliced to the fiber output to increase the damage threshold. At 100 kHz a peak power of 351 kW was measured for an average power of 59.9 W. The efficiency is then 70 %. This good efficiency shows that the composition was well optimized. We also studied the influence of the bending radius on the slope efficiency. We do not observe any slope efficiency reduction down to 25 cm bending diameter. It decreased to 68 % for the 20 cm bending diameter. The laser shows a quasisinglemode output beam with a good quality factor M² of 1.2.

Background Brain metastases often occur in cancer evolution. They are not only responsible for death but also for disorders affecting the quality of life and the cognitive functions. Management of brain metastases usually consists in multi-modality treatments, including neurosurgery, whole brain radiotherapy (WBRT), and more recently radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), systemic treatment (chemotherapy or targeted therapy), combined or not with corticosteroids. Almost 20% of brain metastases can present recent (within 15 days) bleeding signs on neuro-imagery. In these conditions, WBRT is the usual treatment. Yet, patients may benefit from a more aggressive strategy with SRT or FSRT. However, these options were suspected to possibly major the risk of brain haemorrhage, although no scientifically proven. Radiation oncologists therefore usually remain reluctant to deliver SRS/FSRT for bleeding brain metastases. It is therefore challenging to establish a standard of care for the treatment of bleeding brain metastases. We propose a phase II trial to simultaneously assess safety and efficacy of FSRT to manage brain metastases with hemorrhagic signal. Methods The STEREO-HBM study is a multicenter two-step non-randomised phase II trial addressing patients with at least one bleeding brain metastasis out of a maximum of 3 brain metastases. Each brain metastasis will be treated with 30 Gy in 3 fractions for 1 week. The main endpoint is based on both safety and efficacy endpoints as proposed by Bryant and Day’s design. Safety endpoint is defined as the rate of bleeding complications 4 months post-FSRT while efficacy endpoint is defined as the 6-month local control rate. Multi-modal MRI will be used to assess intra-tumoral hemorrhagic events before and after treatment. Patients’ quality of life will also be assessed. Discussion Management of bleeding brain metastases is still debated and poorly explored in clinical trials. There is sparse and weak data on the signification of pretreatment intra-tumour haemorrhagic signs or on the risk of brain bleeding complications after FSRT. We expect this first prospective phase 2 trial in this particular setting will allow to clarify the place of FSRT to optimally manage bleeding brain metastases. Trial registration NCT 03696680, registered October, 4, 2018. Protocol version Version 2.1 dated from 2018/11/09.

National audience; Over the last decades, molecular signatures have become increasingly important in oncology and are opening up a new area of personalized medicine. Nevertheless, biological relevance and statistical tools necessary for the development of these signatures have been called into question in the literature. Here, we investigate six typical selection methods for high-dimensional settings and survival endpoints, including LASSO and some of its extensions, component-wise boosting, and random survival forests (RSF). A resampling algorithm based on data splitting was used on nine high-dimensional simulated datasets to assess selection stability on training sets and the intersection between selection methods. Prognostic performances were evaluated on respective validation sets. Finally, one application on a real breast cancer dataset has been proposed. The false discovery rate (FDR) was high for each selection method, and the intersection between lists of predictors was very poor. RSF selects many more variables than the other methods and thus becomes less efficient on validation sets. Due to the complex correlation structure in genomic data, stability in the selection procedure is generally poor for selected predictors, but can be improved with a higher training sample size. In a very high-dimensional setting, we recommend the LASSO-pcvl method since it outperforms other methods by reducing the number of selected genes and minimizing FDR in most scenarios. Nevertheless, this method still gives a high rate of false positives. Further work is thus necessary to propose new methods to overcome this issue where numerous predictors are present. Pluridisciplinary discussion between clinicians and statisticians is necessary to ensure both statistical and biological relevance of the predictors included in molecular signatures.

A new method has permitted the measurement of the refractive index difference between two silica-based materials with an unprecedented accuracy of ±1.10-5 thanks to a novel fiber design associated with a classic Mach-Zehnder interferometer.

Background: Current guidelines recommend performing esophagectomy after endoscopic resection for early esophageal cancer when the risk of lymph node metastasis or residual cancer is found to be significant and endoscopic treatment is therefore noncurative. Our aim was to assess the safety and oncological outcomes of esophagogastric resection in this specific clinical setting. Patients and methods: A retrospective review from 2012 to 2018 was performed at four tertiary referral centers. All patients had a noncurative endoscopic resection of a clinical T1 esophageal cancer, followed by esophagectomy. Outcome measures were the rates of T0N0 specimens, overall survival, disease-free and cancer-specific survival, postoperative morbidity and mortality. Results: A total of 30 patients (13 with squamous cell carcinoma and 17 with adenocarcinoma) were included. The reasons for noncurative endoscopic resection were: positive vertical margins ( n = 12), squamous cell carcinoma with muscularis mucosae or submucosal layer invasion ( n = 3 and 9), adenocarcinoma with deep submucosal invasion ( n = 11), poorly differentiated tumor ( n = 6) and lymphovascular invasion ( n = 6). Overall, 63% of the esophagi were T0N0: most residual lesions were T1a metachronous lesions, and four (13%) patients had advanced pT status ( n = 3) or lymph node metastases ( n = 2). Overall survival, disease-free survival and cancer-specific survival were 83%, 75%, and 90% respectively. A total of 43% of patients had severe postoperative complications, and postoperative mortality was 7%. Conclusion: In this cohort, esophagectomy allowed the resection of residual advanced cancer or lymph node metastases in 13% of cases, at the cost of 43% severe morbidity and 7% mortality. Therefore, the possibility of close follow up needs to be balanced with a highly morbid surgical management in these patients.