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Skillful streamflow forecasts provide key support to several water‐related applications. Because of the critical impact of initial conditions (ICs) on forecast accuracy, ever‐growing interest is focused on improving their estimates via data assimilation (DA). This study aims to assess the sensitivity of the DA‐based estimation of forecast ICs to several sources of uncertainty and the update of different model states and parameters of a lumped conceptual rainfall–runoff model over 232 watersheds in France. The performance of two sequential ensemble‐based techniques, namely, the ensemble Kalman filter (EnKF) and the particle filter (PF), is compared in terms of efficiency and temporal persistence (up to 10 days) of the updating effect through the assimilation of observed discharges. Several experiments specifically address the impact of the meteorological, state, and parameter uncertainties. Results show that an accurate estimate of the initial level of the routing store of the conceptual model ensures the most benefit to the DA‐based estimation of forecast ICs. While EnKF‐based forecasts outperform PF‐based ones when accounting for meteorological uncertainty, the more comprehensive representation of the state uncertainty makes it possible to greatly improve the accuracy of PF‐based predictions, with a longer‐lasting updating effect. Conversely, forecasting skill is undermined when accounting for parameter uncertainty, owing to the change in hydrological responsiveness. This study extensively addresses several sensitivity analyses in order to provide useful recommendations for designing DA‐based streamflow forecasting systems and for diagnosing possible deficiencies in existing systems. Plain Language Summary: Accurate streamflow forecasts are of critical importance to several real‐time applications, such as water resource management and flood prevention. The predictive accuracy critically depends on the quality of the forecast initial conditions. Data assimilation (DA) techniques are increasingly being implemented to obtain the most likely estimation of forecast initial conditions through the assimilation of observed hydrological variables. This study compares the performances of two DA techniques, namely the Ensemble Kalman filter and the Particle filter, in terms of both efficiency and temporal persistence (up to 10 days) of the updating effect. The analysis addresses the impact of different sources of uncertainty and the update of different model states and parameters of a lumped conceptual hydrological model, when assimilating observed discharges over 232 watersheds in France. Results show that an accurate estimation of the initial level of the routing store ensures the most benefit of DA, as this state variable is the most correlated with observations. A comprehensive representation of the state uncertainty generally improves the estimation of the forecast initial conditions resulting from the assimilation. While the Ensemble Kalman filter outperforms the Particle filter in the short term, this latter guarantees a longer‐lasting updating effect over the forecast horizon. Key Points: Estimation of forecast initial level of the routing store of a conceptual hydrological model ensures the most benefit from data assimilationUpdating forecast initial conditions using the ensemble Kalman filter results in a greater improvement in predictive accuracy in the short termThe particle filter guarantees a longer‐lasting effect of the update of initial conditions over the forecast horizon [ABSTRACT FROM AUTHOR]

In semidistributed hydrological modeling, sequential calibration usually refers to the calibration of a model by considering not only the flows observed at the outlet of a catchment but also the different gauging points inside the catchment from upstream to downstream. While sequential calibration aims to optimize the performance at these interior gauged points, we show that it generally fails to improve performance at ungauged points. In this paper, we propose a regularization approach for the sequential calibration of semidistributed hydrological models. It consists in adding a priori information on optimal parameter sets for each modeling unit of the semidistributed model. Calibration iterations are then performed by jointly maximizing simulation performance and minimizing drifts from the a priori parameter sets. The combination of these two sources of information is handled by a parameter k to which the method is quite sensitive. The method is applied to 1,305 catchments in France over 30 years. The leave‐one‐out validation shows that, at locations considered as ungauged, model simulations are significantly improved (over all the catchments, the median KGE criterion is increased from 0.75 to 0.83 and the first quartile from 0.35 to 0.66), while model performance at gauged points is not significantly impacted by the use of the regularization approach. Small catchments benefit most from this calibration strategy. These performances are, however, very similar to the performances obtained with a lumped model based on similar conceptualization. Key Points: Sequential calibration without regularization yields low performance in small ungauged catchmentsSequential calibration constrained by regularization strategy helps improving model regionalizationRegularization benefits from a priori parameter values of neighboring catchments [ABSTRACT FROM AUTHOR]

The French Observatory of Food Quality (Oqali) aims at collecting all nutritional data provided on the labels of processed foods (nutritional information and composition), at the branded products level, in order to monitor changes in food composition (including reformulation) and nutritional labelling over time. This study involved a cross-sectional analysis of both the range of processed foods available and the associated nutritional information labelling according to the type of brand (national brands, retailer brands, entry-level retailer brands, hard discount and specialised retailer brands). On the basis of the data collected for 16 081 products from 24 food sectors between 2008 and 2011, the range of entry-level retailer brands was concentrated on the most basic and traditional recipes: for instance among Fresh dairy products, there were 30% Fresh creams, liégeois and flavoured jellied milk (n = 19), 24% Classic sweet yogurts (n = 15), and 17% Classic plain fresh cheeses with no added sugar (n = 11), but no Light and/or sweetened fresh dairy desserts (n = 0). Analysis of nutritional information labelling showed that retailer brand products carried the highest frequency of nutrition labelling (94%), guideline daily amounts (54%), and serving sizes (78%). National brand products displayed the highest frequency of claims (28% for nutrition claims and 8% for health claims). Entry-level retailer brand products displayed the lowest amount of nutritional information. [ABSTRACT FROM AUTHOR]

Summary: Background: Decreased sleep duration and altered sleep quality are risk factors for obesity in youth. Structured exercise training has been shown to increase sleep duration and improve sleep quality. Objectives: This study aimed at evaluating the impact of exercise training for improving sleep duration, sleep quality and physical activity in obese adolescents (OB). Methods: Twenty OB (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m−2) and 20 healthy‐weight adolescents (HW) completed an overnight polysomnography and wore an accelerometer (SenseWear Bodymedia) for 7 days. OB participated in a 12‐week supervised exercise‐training programme consisting of 180 min of exercise weekly. Exercise training was a combination of aerobic exercise and resistance training. Results: Sleep duration was greater in HW compared with OB (P < 0.05). OB presented higher apnoea‐hypopnoea index than HW (P < 0.05). Physical activity (average daily metabolic equivalent of tasks [METs]) by accelerometer was lower in OB (P < 0.05). After exercise training, obese adolescents increased their sleep duration (+64.4 min; effect size: 0.88; P = 0.025) and sleep efficiency (+7.6%; effect size: 0.76; P = 0.028). Physical activity levels were increased in OB as evidenced by increased steps per day and average daily METs (P < 0.05). Improved sleep duration was associated with improved average daily METs (r = 0.48, P = 0.04). Conclusion: The present study confirms altered sleep duration and quality in OB. Exercise training improves sleep duration, sleep quality and physical activity. [ABSTRACT FROM AUTHOR]

Background Exercise training has been shown to improve cardiometabolic health in obese adolescents. Objectives Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles. Methods We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents ( OB) (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m−2) and 20 age- and gender-matched normal-weight adolescents ( NW). Body composition was assessed by magnetic resonance imagery. Peak aerobic capacity and maximal fat oxidation were evaluated during specific incremental exercise tests. OB participated in a 12-week exercise-training programme. Results OB presented lower peak aerobic capacity (24.2 ± 5.9 vs. 39.8 ± 8.3 mL kg−1 min−1, P < 0.05) and maximal fat oxidation compared with NW ( P < 0.05). OB displayed greater F2t- Isoprostanes (20.5 ± 6.7 vs. 13.4 ± 4.2 ng mmol−1 creatinine), Interleukin-1 receptor antagonist (IL-1Ra) (1794.8 ± 532.2 vs. 835.1 ± 1027.4 pg mL−1), Tumor Necrosis Factor-α (TNF-α) (2.1 ± 1.2 vs. 1.5 ± 1.0 pg mL−1), Soluble Tumor Necrosis Factor-α Type II Receptor (sTNFαRII), leptin, insulin, homeostasis model assessment of insulin resistance, version 2 ( HOMA2- IR), high-sensitive C-reactive protein, triglycerides and lower adiponectin and high-density lipoprotein cholesterol (all P < 0.05). After exercise training, despite lack of weight loss, VO2peak (mL.kg−1.min−1) and maximal fat oxidation increased ( P < 0.05). IL-1 Ra and IFN-gamma-inducible protein 10 (IP-10) decreased ( P < 0.05). Insulin and HOMA2- IR decreased (14.8 ± 1.5 vs. 10.2 ± 4.2 μ UI m L−1 and 1.9 ± 0.8 vs. 1.3 ± 0.6, respectively, P < 0.05). Change in visceral fat mass was inversely associated with change in maximal fat oxidation (r = −0.54; P = 0.024). The subgroup of participants that lost visceral fat mass showed greater improvements in triglycerides, insulin resistance and maximal fat oxidation. Conclusion Our data confirms the role of exercise training on improving the inflammatory profile and insulin resistance of OB in the absence of weight loss. However, those who lost a greater amount of visceral fat mass showed greater benefits in terms of insulin profile, triglycerides and maximal fat oxidation. [ABSTRACT FROM AUTHOR]

Low-flow simulation and forecasting remains a difficult issue for hydrological modellers, and intercomparisons can be extremely instructive for assessing existing low-flow prediction models and for developing more efficient operational tools. This research presents the results of a collaborative experiment conducted to compare low-flow simulation and forecasting models on 21 unregulated catchments in France. Five hydrological models (four lumped storage-type models -- Gardenia, GR6J, Mordor and Presages -- and one distributed physically oriented model -- SIM) were applied within a common evaluation framework and assessed using a common set of criteria. Two simple benchmarks describing the average streamflow variability were used to set minimum levels of acceptability for model performance in simulation and forecasting modes. Results showed that, in simulation as well as in forecasting modes, all hydrological models performed almost systematically better than the benchmarks. Although no single model outperformed all the others for all catchments and criteria, a few models appeared to be more satisfactory than the others on average. In simulation mode, all attempts to relate model efficiency to catchment or streamflow characteristics remained inconclusive. In forecasting mode, we defined maximum useful forecasting lead times beyond which the model does not bring useful information compared to the benchmark. This maximum useful lead time logically varies between catchments, but also depends on the model used. Simple multi-model approaches that combine the outputs of the five hydrological models were tested to improve simulation and forecasting efficiency. We found that the multi-model approach was more robust and could provide better performance than individual models on average. [ABSTRACT FROM AUTHOR]

Models with a fixed structure are widely used in hydrological studies and operational applications. For various reasons, these models do not always perform well. As an alternative, flexible modelling approaches allow the identification and refinement of the model structure as part of the modelling process. In this study, twelve different conceptual model structures from the SUPERFLEX framework are compared with the fixed model structure GR4H, using a large set of 237 French catchments and discharge-based performance metrics. The results show that, in general, the flexible approach performs better than the fixed approach. However, the flexible approach has a higher chance of inconsistent results when calibrated on two different periods. When analysing the subset of 116 catchments where the two approaches produce consistent performance overmultiple time periods, their average performance relative to each other is almost equivalent. From the point of view of developing a well-performing fixed model structure, the findings favour models with parallel reservoirs and a power function to describe the reservoir outflow. In general, conceptual hydrological models perform better on larger and/or wetter catchments than on smaller and/or drier catchments. The model structures performed poorly when there were large climatic differences between the calibration and validation periods, in catchments with flashy flows, and in catchments with unexplained variations in low flow measurements. [ABSTRACT FROM AUTHOR]

Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10–90) years, 58% were women. Median tumour size was 37 mm (4–220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages. • EHE is an ultrarare sarcoma with a specific natural history. • A large proportion of EHE present as multifocal and or metastatic disease at diagnosis. • The OS and PFS of patients with advanced EHE is superior to that of other sarcomas. • Male, pleural, bone sites, and multifocality correlate to worse OS and PFS. • Prolonged PFS and OS can be observed after first line medical treatment. [ABSTRACT FROM AUTHOR]

Introduction: Adolescents and young adults (AYA) with cancer undergo physical transformations due to disease and treatments occurring alongside puberty and adolescence. Although physical activity is recommended for its benefits, its practice among AYA with cancer remains insufficient. The aim of the Éducation Thérapeutique et Activité Physique: Engagement des Adolescents et Jeunes Adultes atteints de cancer study is to identify the evolution of AYA with cancer medical knowledge and powers (power to act, to express oneself) over life and cancer care, and their role in commitment in adapted physical activity (APA) and therapeutic patient education during and after oncological treatments., Methods and Analysis: This prospective mixed methods monocentre study will be conducted in a French comprehensive cancer centre. Observations will be conducted two times a week during medical consultations, APA interventions and therapeutic education sessions for AYA with cancer. Semidirective interviews will involve 70 participants, including AYA with cancer aged 15-25, health professionals, APA teachers and parents. Quantitative data will be collected on AYA's social characteristics and participation in physical activity intervention and therapeutic education sessions. A correspondence factor analysis will supplement inductive analysis of ethnographic qualitative data, involving patient coresearchers. The results will help to improve the understanding of AYAs' medical knowledge and powers, their commitment in physical activity and to develop strategies to increase their participation., Ethics and Dissemination: This study complies with reference methodology MR004 of the French National Data Protection Authority and was registered by the Data Protection Officer of the Leon Berard Cancer Center on the activity registry of the institution (Ref. N°R201-004-259; 5 July 2022). Ethics approval has been obtained from the Centre Léon Bérard ethics board (Ref. N°2022-006; 20 July 2022). Oral informed consent will be obtained from all participants before data collection. The results of this study will be published in peer-reviewed scientific journals, national and international conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010., Patients and Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020., Results: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers., Conclusions: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This multi-cohort trial explored the efficacy and safety of regorafenib for patients with advanced sarcomas of bone origin; this report details the cohort of patients with metastatic or locally advanced chondrosarcoma (CS), progressing after prior chemotherapy., Patients and Methods: Patients with CS, progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progressive disease. The primary endpoint was progression-free rate (PFR) at 12 weeks. With one-sided α of 0.05, and 80% power, at least 16/24 progression-free patients at 12 weeks were needed for success (P0 = 50%, P1 = 75%)., Results: From September 2014 to February 2019, 46 patients were included in the CS cohort, and 40 patients were evaluable for efficacy: 16 on placebo and 24 on regorafenib. Thirteen patients (54.2%; 95% CI [35.8%-[) were non-progressive at 12 weeks on regorafenib versus 5 (31.3%; 95% CI [13.2%-[);) on placebo. Median PFS was 19.9 weeks on regorafenib, and 8.0 on placebo. Fourteen placebo patients crossed over to regorafenib after progression. The most common grade ≥3 treatment-related adverse events on regorafenib included hypertension (12%), asthenia (8%), thrombocytopenia (8%) and diarrhoea (8%). One episode of fatal liver dysfunction occurred on regorafenib., Conclusion: Although the primary endpoint was not met statistically in this small randomised cohort, there is modest evidence to suggest that regorafenib might slow disease progression in patients with metastatic CS after the failure of prior chemotherapy., Clinical Trial Registration: The trial is registered at ClinicalTrials.gov (NCT02389244)., Competing Interests: Conflict of interest statement FD received travel grants from Pharmamar, and Leo Pharma attended advisory boards for Bayer, Lilly. CC attended advisory boards for Leo Pharma, OM attended advisory boards and chaired meetings with Amgen, Astra Zeneca, Bayer, Bleuprint, Eli Lilly, Roche, Servier, PBR received travel grants form Pfizer, Takeda, JYB receives research support and honoraria from Eisei, Eli Lilly, MSD, BMS, GSK, Ignyta, Novartis, Pharmamar and Roche unrelated to this work, and AI, CP, NP, OC, LC, CD, MC, LM, MR, EB, SC, FB, CS, SPN, CB, VV, AH, ESB, have declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Young age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups (<40, 40 to 60 and > 60 years(y))., Methods: ESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014., Results: Among 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were <40, 40-60 and > 60 y respectively. Pts <40 had significantly more aggressive presentations than other age groups: more frequent HER2+ (25.7 vs 15.3% in >60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts <40, 40-60 and > 60y, respectively (p < 0.0001). Compared to pts <40y, older pts had a statistically significant higher risk of death (all causes of death included), although of limited clinical value (HR = 1.1, IC 95%:1.01-1.20). There was a significant trend for better OS in pts <40y with HER2+ and luminal diseases. A possible explanation is a greater use of anti-Her2 therapies as first-line treatments: 86.6, 81.9 and 74.9% for pts <40, 40-60 and > 60y, respectively (p < 0.0001)., Conclusion: Although young age seems associated with more aggressive presentations at diagnosis of MBC, it has no deleterious effect on OS in this large series., Competing Interests: Declaration of competing interest Co-authors having declared no conflict of interests: Sophie Frank, Matthieu Carton, Coraline Dubot, Barbara Pistilli (GR), Audrey Mailliez (COL), Christelle Levy (CFB), Véronique D’Hondt (ICM), Marc Debled (IB), Thomas Vermeulin (CHB), Bruno Coudert (CGFL), Christophe Perrin (CEM), Anthony Gonçalves (IPC), Lionel Uwer (ICL), Jean-Marc Ferrero (CAL), Jean-Christophe Eymard (IJG), Thierry Petit (CPS), Marie-Ange Mouret-Reynier (CJP), Anne Patsouris (ICO PP), Tahar Guesmia (R&D Unicancer), Thomas Bachelot (CLB), Mathieu Robain (R&D Unicancer), Paul Cottu. Mario campone: Advisory Board: Consulting fees to my Institut:Astra ZENECA, Novartis, Abbvie, Sanofi, Pfizer, Sandoz, ACCORD. Personal fees to Lilly, G1 Therapeutic Consultant: Fees to my Institute: Pierre Fabre Oncology; Sanofi; Novartis; Servier. Speaker bureau: Personnal fees Novartis, Lilly Travel: Pfizer, Novartis, Roche, Astra Zeneca. Barbara Pistilli:P ersonal fees from AstraZeneca, Pfizer, Myriad, Pierre Fabre and non-financial support from Pfizer, Puma and Merus, Novartis outside the submitted work Florence Dalenc: Advisory Board: Novartis, Pfizer, Lilly Travel: Pfizer, Novartis, Roche, Astra Zeneca Paul Cottu: Advisory Board: Novartis, Pfizer, Lilly, Roche Travel: Pfizer, Novartis, Roche, Astra Zeneca., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The Time to First Metastatic Recurrence (TFMR) could be considered as an indirect reflection of the tumour growth kinetics which plays an important role in cancer. Molecular subtypes such as expression of estrogen receptor are known predictive factors of TFMR. The CinéBreast study aimed to identify predictive factors of the time to TFMR., Methods: The French Epidemiological Strategy and Medical Economics (ESME) Metastatic Breast Cancer (MBC) Database (NCT03275311) was used, which contains data from a cohort of metastatic breast cancer patients from 2008 to 2016 using retrospective data collection. It is a national multi-centre database. The impact of TFMR on overall survival (OS) since first metastasis was also evaluated., Results: Among 16 702 patients recorded in the ESME MBC database, 10 595 had an initially localised breast cancer with hormone receptor (HR) and HER2 status available, with a metastatic recurrence. Median follow up was 56 months. Median TFMR was 59 months (<24: 20%, 24-60: 31%, 60-120: 25%, >120: 24%). HER2+ and TNBC were respectively 4 times and 12 times (p < 0.0001) more likely to have a recurrence within 2 years when compared to the luminal subgroup. Short TFMR and HR-/HER2-subtype significantly correlated with a poor OS in multivariate analysis. Some patients with MBC (20% in HER2+, 10% in ER+/HER2-and <5% in the ER-/HER2-) were long-term survivors in all 3 subgroups., Conclusions: In this large-scale real-life data study, patients with a TNBC metastatic recurrence had a shorter TFMR. Short TFMR significantly correlated with worse overall survival., Competing Interests: Declaration of competing interest TB reports grants, personal fees, and non-financial support from Roche, grants, personal fees, and non-financial support from Novartis, grants and personal fees from AstraZeneca, outside the submitted work. MC reports personal fees from Roche, during the conduct of the study; grants and personal fees from Novartis, personal fees from Astra Zeneca, personal fees from Menarini, outside the submitted work. WJ reports personal fees and non-financial support from Roche, outside the submitted work. AG reports grants, personal fees, and non-financial support from Roche, during the conduct of the study. TP reports non-financial support and other support from Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the OS2006 study, patients younger than 18 years were treated with a methotrexate-based regimen (MTX), patients older than 25 years with a doxorubicin-cisplatin-ifosfamide-based regimen (API-AI), whereas patients aged 18-25 years received either API-AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API-AI. Preoperative chemotherapy combined three doxorubicin-ifosfamide-cisplatin (API) and two doxorubicin-ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin-ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide-ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18-67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety-six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28-48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow-up of 4.8 years, the 5-year event-free survival and overall survival rates were 46% (95% CI 36-56) and 57% (95% CI 47-67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API-AI proved feasible with no excess of toxicity, and favourable activity despite poor-prognosis factors., (© 2019 UICC.)

Background: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry., Patients and Methods: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497)., Results: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]., Conclusion: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

This paper summarizes the results obtained within the framework of the French PROMOTO Project (PROtection of the MOTOrcyclist). The aim of this project was to analyze the impact between a motorcycle and a light vehicle from an epidemiological, accidentological and biomechanical point of view. The results have made it possible to outline the most frequent accident configurations such as the "turn on the left" and the most common injuries sustained by motorized two-wheelers (head and trunk). The biomechanic analysis has enabled a better understanding of the kinematics involved in an impact between a motorized two-wheeler and a light vehicle in various accident configurations (chronology and speed impact). While it is well known that motorcyclists frequently receive life threatening injuries to the head, spine and torso, this paper has been able to observe specific injury mechanisms such as pelvis impacts against the vehicle fuel tank and hyper-extension of the neck due to head impact on passenger cars., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To assess the impact of an information leaflet on the behavior and knowledge of pregnant women about the risks of HIV infection during pregnancy., Patients and Methods: Comparative prospective study conducted in two phases from March 1 to September 30, 2007 on patients presenting for the first time in antenatal care at the Maternity Hospital of Tours (n=539). During the first phase, only a self-questionnaire was given during the second an informative brochure has been attached to the questionnaire., Results: Currently 25.1% of pregnant women have not made a test during their pregnancy. This rate decreases to 12.9% when the test is routinely offered. It falls to 8.2% with the introduction of an informative brochure. The test was imposed in 28.7% of patients. Some risks of transmission of HIV, including those specific to pregnancy, are undervalued. A negative test before the pregnancy is the main reason for refusal of antenatal screening. A high level of education was the only risk factor identified for refusal. They are better informed as shown by the higher rate of correct answers about the risks of HIV transmission and antenatal screening. We hypothesize that the women who pursued graduate studies evaluate the risk of infection before accepting or refusing the test., Conclusion: The study shows that the distribution of an informative brochure on advanced prenatal screening, increased the number of women performing the test and improved their knowledge about risks of transmission, especially from mother to the child., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: In France, there are no good practice guidelines or a regulatory framework for the initiation of long term non-invasive ventilation (NIV)., Methods: The ANTADIR federation set up a working party to examine the feasibility of new methods of initiation of NIV and to consider the possibility of initiation in the home. Two problems were considered: (1) logistical and technical requirements, (2) the responsibilities of the professions involved and the regulatory framework., Results: Clinical effectiveness, improvement in quality of life and adherence to treatment are similar whether NIV is initiated in hospital or at home. Domiciliary management is possible only when the patient is clinically stable. It should be undertaken by a competent physician or, on medical prescription, by a physiotherapist. A nurse or trained technician may check the apparatus but should not initiate NIV alone. Installation of domiciliary NIV should be considered under the following conditions: patients with spontaneous ventilation, availability of urgent assistance and appropriate family support. Close surveillance of the quality of ventilation is necessary, whether in hospital or at home. For the initiation of domiciliary NIV each professional involved needs a clear understanding of his/her role., Conclusion: Academic societies should propose good practice guidelines for the initiation of NIV. Domiciliary initiation is possible under certain conditions and the results are as good as those obtained in hospital., (Copyright © 2010. Published by Elsevier Masson SAS.)

Patients' associations are an integral but often overlooked component of the French healthcare system dominated by the medical profession. Very few patients' associations exist to enable patients to self-manage into physical activity programmes. The aim of this qualitative study was to examine perceived motives for regular physical activity in male and female individuals, with type 2 diabetes involved in one French patients' association, called 'Move for Health'. Twenty-three adults (14 women and 9 men) with type 2 diabetes ranging in age from 35 to 78 volunteered to participate. The participants undertook regular physical activities autonomously with some medico-sporting educators' help. Results showed that participants reported intrinsic motives such as enjoyment, interest, fun, stimulation and highlighted gender differences. Female participants were more likely than male participants to emphasise the importance of emotional support obtained from the group meetings, and the pleasure of doing something together, and male participants emphasised the knowledge acquisition and skill development for disease control. Moreover, female participants indicated the importance of the sense of well-being and the positive body image related to regular physical activity, and male participants underlined the strength of the relationship between physical activity and health-promoting behaviours. This study provides insights into how gender motives are related to the interest and usefulness of physical activities in the management of diabetes. Findings lend support to the setting up of this type of patients' association in the French healthcare system and underline its contribution to self-determination and the behaviour change process in people with diabetes.

A thorough questionnaire-based survey of French diabetes networks depicts an accurate description of the services they offer, in particular concerning physical activity. Often considered as less important than medicinal monitoring and dietetics, physical activity is at the core of a new professional dynamic. Practical sessions of adapted physical activity are presently offered in half the networks, as either one-time awareness-raising sessions or a complete series of sessions. Sports medicine educators seem to constitute an emerging professional group within a framework which aims to complement information provided to patients by skills-building through group sessions. Two distinct perspectives emerge as being linked to intervention methods: the first one aims to educate about physical activity, while the second aims to educate through physical activity.

Aims: To compare respiratory status in dairy farmers with that of non-farming controls., Methods: Longitudinal study in the Doubs (France). From a cohort constituted in 1994 (T1), 215 (81.1%) dairy farmers and 110 (73.8%) controls were reevaluated in 1999 (T2). The protocol comprised a medical and occupational questionnaire, spirometric tests at both evaluations, allergological tests at T1, and a non-invasive measure of blood oxygen saturation (SpO2) at T2., Results: In 1999 analyses, the prevalence of chronic bronchitis was higher (p = 0.013), and FEV1/VC (p < 0.025) and SpO2 (-0.7%, p < 0.01) lower in dairy farmers than in controls. In a multiple linear regression model, farming, age, and smoking were significantly and inversely correlated with SpO2. In the whole population, the mean annual decline in FEV1 and FEV1/VC was -13.4 ml and -0.30%, respectively. Farming was associated with an accelerated decline in FEV1/VC (p < 0.025) after adjustment for covariates. No relation between allergy and respiratory function changes was observed, except for FEF25-75., Conclusions: This prospective study shows that dairy farming is associated with an excess of chronic bronchitis, with a moderate degree of bronchial obstruction and a mild decrease in SpO2.

Objectives: To explore the perceptions of health and physical activity, and the associations between these two areas from a theoretical lifestyle perspective., Methods: Data was collected by means of a self-administered questionnaire, among 3019 adults attending centres for preventive medicine in France. Correspondence analysis examined the significance of the relationships between perceptions of health and perceptions of sports and physical activity., Results: Four principal types of subjects emerged from the factor analyses expressing four different lifestyle patterns. "Non physically active lifestyle: a feeling of not being healthy", "Physically active lifestyle, pleasure/leisure-oriented", "Necessarily physically active lifestyle, regardless of health", "Physically active lifestyle aimed at stress relief"., Conclusions: The sociological approach helps tackle sports and physical activity as behaviour patterns but also and especially as a health orientation connected with the socio-economical climate. This approach also gives sports practice back its meaningful cultural dimension.

Both volume preset and pressure preset ventilators are available for domiciliary nasal ventilation. Owing to their technical characteristics, it has been suggested that impaired ventilatory mechanics might cause a drop in the tidal volume (Vt) delivered by pressure preset devices, thereby placing mechanical ventilation at risk of inefficacy. We have assessed two ventilator systems (one pressure preset and one volume preset) with regard to the tidal volume and end-tidal carbon dioxide tension (PetCO(2)) changes that may be achieved in a group of awake patients with stable chronic respiratory failure (CRF). Eleven patients with stable CRF were ventilated in the assist/control mode for two consecutive one-hour periods. One ventilator was tested each hour, in random order. The VIGIL'AIR(R) system was used to record Vt, Respiratory Rate (RR), and Inspiratory/Expiratory ratio (I/E). The deviation E (E=preset value - measured value) was calculated for each measurement. Changes in PetCO(2) and arterial oxygen saturation were determined respectively by a capnometer and a pulse oximeter. Comparison of the mean deviation of Vt calculated for the two ventilators revealed a difference in patients with chronic obstructive pulmonary disease (COPD). The deviation was greatest with the pressure preset ventilator (PPV), which gave mean measured values higher than the mean preset values. The same comparison failed to reveal any difference in restrictive CRF. Comparison of the volume preset and pressure preset ventilators for RR, I/E and PetCO(2) did not reveal any difference. Compared to the volume preset ventilator, the efficacy of PPV to ventilate is not affected by the restrictive or obstructive nature of CRF. Our results show that pressure-preset ventilator is an adequate alternative to the volume-preset device for daytime non invasive ventilation in chronic respiratory insufficiency.

Background: Human dirofilariosis is endemic in southern France. The causal agent is Dirofilaria repens transmitted to man by mosquitos. The human organism is an accidental host while the dog is the reservoir. Approximately 60 cases have been reported in France, mainly in southern continental areas and Corsica. Most cases involve subcutaneous and occular manifestations., Case Report: A 47-year old woman living in the Var department in southern france consulted for a subcutaneous nodule with the aspect of an epidermoid cyst. At incision, the nodule was found to contain a helminth found at parasite examination to be Dirofilaria repens., Discussion: The prevalence of endemic subcutaneous dirofilariosis is probably underestimated as the clinical expression is non-specific and spontaneous cure is common. The diagnosis of epidermoid cyst is frequently suggested. History taking does not reveal travel to intertropical areas. The helminth is discovered when the nodule is opened, also providing successful cure.

We report a new case of Ofuji papuloerythroderma. There was no obvious sign of lymphoma or underlying malignancy. This is the 7th European case of papuloerythroderma. This recently described clinical entity is characterized by a pruritic eruption of widespread red-brown flat papules sparing the skin folds, with eosinophilia. The recognition, report and follow-up of further cases are necessary to clarify its relationship with paraneoplastic syndromes, hypereosinophilic syndrome, or prelymphoma skin eruptions.

We report a case of focal epithelial hyperplasia in a child born in France of Algerian parents. The clinical appearance was unusual in that certain lesions were verrucous and pediculate. A virological study revealed the presence of papillomavirus 32, one of the two types of HPV specifically associated with this entity.