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The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

An exemplary urban adapter, the wild boar (Sus scrofa) has successfully colonized urban ecological niches worldwide. Improvement of strategies for optimal management of urban wild boar need to gather more empirical evidence of their spatial ecology. This study is based on GPS tracking and capture-mark-recapture (CMR) of 10 and 59 wild boar, respectively, captured in Bordeaux Metropolis (France). It shows that wild boar have become urban dwellers, with intra-urban home ranges varying from 1.3 to 64.6 km 2 (MCP 100 %) and from 0.5 to 9.6 km 2 (KDE 95 %), depending on urban conditions. CMR results confirm the low propensity to move away from urban areas (with a mean distance of 2 km between capture and recapture sites), despite a relatively low one-year survival rate since capture (47.5 %), primarily attributable to removal efforts. Wild boar strongly depended on urban woods, mostly during daytime resting, and highly frequented urban meadows during night foraging. Their use of urban agricultural areas was minimal, but they were mostly monitored following corn and grape harvests. Wild boar mitigated the risk associated with close proximity to humans by: a nocturnal activity (72.2 % of active locations registered from sunset to sunrise), which could also be partially attributed to their sensitivity to heat; a strong use of covered habitats, especially during daytime resting and when close to buildings and roads; and a low mobility during night-time foraging (1974 m average daily distance travelled). Moreover, we demonstrate high inter- and intra-individual variability in the spatio-temporal behaviour of urban wild boar. Finally, we discuss the gap between these results and the narratives surrounding the spatial ecology of urban wild boar. Our results not only confirm the species' ability to adapt to urban environments, but also highlight their behavioural flexibility, underscoring the relevance of significant changes in representations and management activities to mitigate human-urban wild boar conflicts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Fermented foods, including cheeses, have garnered increased interest in recent years for their potential health benefits. This study explores the biological properties of eight French raw-milk cheeses-goat cheese, Saint-Nectaire, Cantal, Bleu d'Auvergne, Roquefort, Comté, Brie de Meaux, and Epoisses-on oxidative processes using both in vivo ( Caenorhabditis elegans ) and in vitro (human leukocytes) models. A cheese fractionation protocol was adapted to study four fractions for each cheese: a freeze-dried fraction (FDC) corresponding to whole cheese, an apolar (ApE), and two polar extracts (W40 and W70). We showed that all cheese fractions significantly improved Caenorhabditis elegans ( C. elegans ) survival rates when exposed to oxidative conditions by up to five times compared to the control, regardless of the fractionation protocol and the cheese type. They were also all able to reduce the in vivo accumulation of reactive oxygen species (ROS) by up to 70% under oxidative conditions, thereby safeguarding C. elegans from oxidative damage. These beneficial effects were explained by a reduction in ROS production up to 50% in vitro in human leukocytes and overexpression of antioxidant factor-encoding genes ( daf-16 , skn-1 , ctl-2 , and sod-3 ) in C. elegans .

Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response., Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection., Design, Setting, and Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023., Main Outcomes and Measures: An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times., Results: A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001)., Conclusions and Relevance: The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

Aim: To compare walking access times to automated external defibrillators (AEDs) between area-level quintiles of socioeconomic status (SES) in out-of-hospital cardiac arrest (OHCA) cases occurring in 2 major urban regions of Canada and France., Methods: This was an international, multicenter, retrospective cohort study of adult, non-traumatic OHCA cases in the metropolitan Vancouver (Canada) and Rhône County (France) regions that occurred between 2014 and 2018. We calculated area-level SES for each case, using quintiles of country-specific scores (Q5 = most deprived). We identified AED locations from local registries. The primary outcome was the simulated walking time from the OHCA location to the closest AED (continuous and dichotomized by a 3-minute 1-way threshold). We fit multivariate models to analyze the association between OHCA-to-AED walking time and outcomes (Q5 vs others)., Results: A total of 6,187 and 3,239 cases were included from the Metro Vancouver and Rhône County areas, respectively. In Metro Vancouver Q5 areas (vs Q1-Q4), areas, AEDs were farther from (79 % over 400 m from case vs 67 %, p < 0.001) and required longer walking times to (97 % above 3 min vs 91 %, p < 0.001) cases. In Rhône Q5 areas, AEDs were closer than in other areas (43 % over 400 m from case vs 50 %, p = 0.01), yet similarly poorly accessible (85 % above 3 min vs 86 %, p = 0.79). In multivariate models, AED access time ≥ 3 min was associated with decreased odds of survival at hospital discharge in Metro Vancouver (odds ratio 0.41, 95 % CI [0.23-0.74], p = 0.003)., Conclusions: Accessibility of public AEDs was globally poor in Metro Vancouver and Rhône, and even poorer in Metro Vancouver's socioeconomically deprived areas., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This paper aims to prove the feasibility of a 4D monitoring solution (3D modeling and temporal monitoring) for the sandbar and to characterize the species' role in the landscape. The developed solution allows studying the interaction between the river dynamics and vegetation using a network of low resolution and low power sensors. The issues addressed concern the feasibility of implementing a photogrammetry solution using low-resolution sensors as well as the choice of the appropriate sensor and its testing according to different configurations (image capture and storage on the sensor and/or image transmission to a centralization node) and also the detailed analysis of the different phases of the process (camera initialization, image capture, network transmission and selection of the most appropriate standby mode). We reveal that the tiny, low-cost board (ESP32-Cam) can perform a 3D reconstruction and propose using the camera's UXGA (1600, 1200) resolution because of the quality rendering and energy consumption. A multi-node scenario based on a combined Wi-Fi and GSM relay is proposed in the study showing several years of autonomy for the system. Finally, to illustrate the energy cost of the module, we have defined a study process, where we have identified and quantified one by one the different phases of operation of the card for better energy optimization (setup, camera configuration, shooting, saving on SD card, or sending by Wi-Fi). The device is now operational for deployment on the Allier River (France).

Background: During pregnancy a feto-maternal exchange of cells through the placenta conducts to maternal microchimerism (Mc) in the child and fetal Mc in the mother. Because of this bidirectional traffic of cells, pregnant women have also acquired maternal cells in utero from their mother and could transfer grandmaternal (GdM) cells to their child through the maternal bloodstream during pregnancy. Thus, cord blood (CB) samples could theoretically carry GdMMc. Nevertheless this has never been demonstrated., Methods: Using Human Leukocyte Antigen (HLA)-specific quantitative PCR assays on three-generation families, we were able to test 28 CB samples from healthy primigravid women for GdMMc in whole blood (WB) and isolated cells (PBMC, T, B, granulocytes, stem cells)., Findings: Five CB samples (18%) had GdMMc which could not be confounded with maternal source, with quantities 100 fold lower than maternal Mc in WB and PBMC. Risk of aneuploidies and/or related invasive prenatal procedures significantly correlated with the presence of GdMMc in CB (p=0.024). Significantly decreased HLA compatibility was observed in three-generation families from CB samples carrying GdMMc (p=0.019)., Interpretation: Transgenerational transfer of cells could have implications in immunology and evolution. Further analyses will be necessary to evaluate whether GdMMc in CB is a passive or immunologically active transfer and whether invasive prenatal procedures could trigger GdMMc., Funding: Provence-Alpes-Côte d'Azur APEX grant # 2012&#95;06549E, 2012&#95;11786F and 2014&#95;03978) and the Foundation for Medical Research (FRM Grant #ING20140129045)., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objectives: The fact that metabolism and immune function are regulated by an endogenous molecular clock that generates circadian rhythms suggests that the magnitude of ischemia reperfusion, and subsequent inflammation on kidney transplantation, could be affected by the time of the day., Design, Setting, Participants, & Measurements: We evaluated 5026 individuals who received their first kidney transplant from deceased heart-beating donors. In a cause-specific multivariable analysis, we compared delayed graft function and graft survival according to the time of kidney clamping and declamping. Participants were divided into those clamped between midnight and noon ( ante meridiem [am] clamping group; 65%) or clamped between noon and midnight ( post meridiem [pm] clamping group; 35%), and, similarly, those who underwent am declamping (25%) or pm declamping (75%)., Results: Delayed graft function occurred among 550 participants (27%) with am clamping and 339 (34%) with pm clamping (adjusted odds ratio, 0.81; 95% confidence interval, 0.67 to 0.98; P =0.03). No significant association was observed between clamping time and overall death-censored graft survival (hazard ratio, 0.92; 95% confidence interval, 0.77 to 1.10; P =0.37). No significant association of declamping time with delayed graft function or graft survival was observed., Conclusions: Clamping between midnight and noon was associated with a lower incidence of delayed graft function, whereas declamping time was not associated with kidney graft outcomes., (Copyright © 2021 by the American Society of Nephrology.)

Numerical simulation of wildland fire spread is useful to predict the locations that are likely to burn and to support decision in an operational context, notably for crisis situations and long-term planning. For short-term, the computational time of traditional simulators is too high to be tractable over large zones like a country or part of a country, especially for fire danger mapping. This issue is tackled by emulating the area of the burned surface returned after simulation of a fire igniting anywhere in Corsica island and spreading freely during one hour, with a wide range of possible environmental input conditions. A deep neural network with a hybrid architecture is used to account for two types of inputs: the spatial fields describing the surrounding landscape and the remaining scalar inputs. After training on a large simulation dataset, the network shows a satisfactory approximation error on a complementary test dataset with a MAPE of 32.8%. The convolutional part is pre-computed and the emulator is defined as the remaining part of the network, saving significant computational time. On a 32-core machine, the emulator has a speed-up factor of several thousands compared to the simulator and the overall relationship between its inputs and output is consistent with the expected physical behavior of fire spread. This reduction in computational time allows the computation of one-hour burned area map for the whole island of Corsica in less than a minute, opening new application in short-term fire danger mapping., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

RT-qPCR detection of SARS-CoV-2 RNA still represents the method of reference to diagnose and monitor COVID-19. From the onset of the pandemic, however, doubts have been expressed concerning the sensitivity of this molecular diagnosis method. Droplet digital PCR (ddPCR) is a third-generation PCR technique that is particularly adapted to detecting low-abundance targets. We developed two-color ddPCR assays for the detection of four different regions of SARS-CoV-2 RNA, including non-structural (IP4-RdRP, helicase) and structural (E, N) protein-encoding sequences. We observed that N or E subgenomic RNAs are generally more abundant than IP4 and helicase RNA sequences in cells infected in vitro, suggesting that detection of the N gene, coding for the most abundant subgenomic RNA of SARS-CoV-2, increases the sensitivity of detection during the highly replicative phase of infection. We investigated 208 nasopharyngeal swabs sampled in March-April 2020 in different hospitals of Greater Paris. We found that 8.6% of informative samples (n = 16/185, P < 0.0001) initially scored as "non-positive" (undetermined or negative) by RT-qPCR were positive for SARS-CoV-2 RNA by ddPCR. Our work confirms that the use of ddPCR modestly, but significantly, increases the proportion of upper airway samples testing positive in the framework of first-line diagnosis of a French population., (© 2021. The Author(s).)

In patients with isocitrate dehydrogenase (IDH)-mutated acute myeloid leukemia (AML) treated by intensive chemotherapy (IC), prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are of particular interest with the advent of IDH1/2 mutant inhibitors. We retrospectively analyzed 319 patients with newly diagnosed AML (127 with IDH1, 135 with IDH2R140, and 57 with IDH2R172 mutations) treated with IC in 3 Acute Leukemia French Association prospective trials. In each IDH subgroup, we analyzed the prognostic impact of clinical and genetic covariates, and the role of HSCT. In patients with IDH1 mutations, the presence of NPM1 mutations was the only variable predicting improved overall survival (OS) in multivariate analysis (P < .0001). In IDH2R140-mutated AML, normal karyotype (P = .008) and NPM1 mutations (P = .01) predicted better OS. NPM1 mutations were associated with better disease-free survival (DFS; P = .0009), whereas the presence of DNMT3A mutations was associated with shorter DFS (P = .0006). In IDH2R172-mutated AML, platelet count was the only variable retained in the multivariate model for OS (P = .002). Among nonfavorable European LeukemiaNet 2010-eligible patients, 71 (36%) underwent HSCT in first complete remission (CR1) and had longer OS (P = .03) and DFS (P = .02) than nontransplanted patients. Future clinical trials testing frontline IDH inhibitors combined with IC may consider stratification on NPM1 mutational status, the primary prognostic factor in IDH1- or IDH2R140-mutated AML. HSCT improve OS of nonfavorable IDH1/2-mutated AML and should be fully integrated into the treatment strategy., (© 2021 by The American Society of Hematology.)

Background: Human encephalitis represents a medical challenge from a diagnostic and therapeutic point of view. We investigated the cause of 2 fatal cases of encephalitis of unknown origin in immunocompromised patients., Methods: Untargeted metatranscriptomics was applied on the brain tissue of 2 patients to search for pathogens (viruses, bacteria, fungi, or protozoans) without a prior hypothesis., Results: Umbre arbovirus, an orthobunyavirus never previously identified in humans, was found in 2 patients. In situ hybridization and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) showed that Umbre virus infected neurons and replicated at high titers. The virus was not detected in cerebrospinal fluid by RT-qPCR. Viral sequences related to Koongol virus, another orthobunyavirus close to Umbre virus, were found in Culex pipiens mosquitoes captured in the south of France where the patients had spent some time before the onset of symptoms, demonstrating the presence of the same clade of arboviruses in Europe and their potential public health impact. A serological survey conducted in the same area did not identify individuals positive for Umbre virus. The absence of seropositivity in the population may not reflect the actual risk of disease transmission in immunocompromised individuals., Conclusions: Umbre arbovirus can cause encephalitis in immunocompromised humans and is present in Europe., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This paper presents the results of a longitudinal spelling study conducted among 496 school children, from sixth grade (the first year of middle school in France) to ninth grade (the fourth and final year of middle school in France). Its first objective is to examine the evolution of both lexical and grammatical spelling skills in a deep orthography and to present new findings on the advanced mastery of spelling skills. Its second aim is to provide insight into pupils' orthographic knowledge and remaining difficulties at the end of French compulsory schooling. Pupils were assessed using the same text dictation when they were sixth graders and when they were ninth graders. The data show that both lexical and grammatical performance increased from the sixth to ninth grade and that these interact with each other. The qualitative analysis of errors allows points of resistance in the acquisition of French orthography to be highlighted.

Background: Despite their usefulness in perioperative and acute care settings, factor-Xa inhibitor-specific assays are scarcely available, contrary to heparin anti-Xa assay. We assessed whether the heparin anti-Xa assay can (1) be used as a screening test to rule out apixaban, rivaroxaban, fondaparinux, and danaparoid levels that contraindicate invasive procedures according to current guidelines (>30 ng·mL-1, >30 ng·mL-1, >0.1 µg·mL-1, and >0.1 IU·mL-1, respectively), (2) quantify the anticoagulant level if found significant, that is, if it exceeded the abovementioned threshold., Methods: In the derivation cohort then in the validation cohort, via receiver operating characteristics (ROC) curve analysis, we evaluated the ability of heparin anti-Xa assay to detect levels of factor-Xa inhibitors above or below the abovementioned safety thresholds recommended for an invasive procedure (screening test). Among samples with relevant levels of factor-Xa inhibitor, we determined the conversion factor linking the measured level and heparin anti-Xa activity in a derivation cohort. In a validation cohort, the estimated level of each factor-Xa inhibitor was thus inferred from heparin anti-Xa activity. The agreement between measured and estimated levels of factor-Xa inhibitors was assessed., Results: Among 989 (355 patients) and 756 blood samples (420 patients) in the derivation and validation cohort, there was a strong linear relationship between heparin anti-Xa activities and factor-Xa inhibitors measured level (r = 0.99 [95% confidence interval {CI}, 0.99-0.99]). In the derivation cohort, heparin anti-Xa activity ≤0.2, ≤0.3, <0.1, <0.1 IU·mL-1 reliably ruled out a relevant level of apixaban, rivaroxaban, fondaparinux, and danaparoid, respectively (area under the ROC curve ≥0.99). In the validation cohort, these cutoffs yielded excellent classification accuracy (≥96%). If this screening test indicated relevant level of factor-Xa inhibitor, estimated and measured levels closely agreed (Lin's correlation coefficient close to its maximal value: 95% CI, 0.99-0.99). More than 96% of the estimated levels fell into the predefined range of acceptability (ie, 80%-120% of the measured level)., Conclusions: A unique simple test already widely used to assay heparin was also useful for quantifying these 4 other anticoagulants. Both clinical and economic impacts of these findings should be assessed in a specific study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Background: Although manganese (Mn) is an essential nutrient, recent research has revealed that excess Mn in early childhood may have adverse effects on neurodevelopment., Methods: We estimated daily total Mn intake due to breast milk at average body weights by reviewing reported concentrations of breast milk Mn and measurements of body weight and breast milk intake at 3 weeks, 4.25 months, 7 months, and 18 months. We compared these figures to the Mn content measured in 44 infant, follow-up, and toddler formulas purchased in the United States and France. We calculated Mn content of formula products made with ultra-trace elemental analysis grade water (0 μg Mn/L) and with water containing 250 μg Mn/L, a concentration which is relatively high but less than the World Health Organization Health-based value of 400 μg Mn/L or the United States Environmental Protection Agency Health Advisory of 350 μg Mn/L., Results: Estimated mean daily Mn intake from breast milk ranged from 1.2 μg Mn/kg/day (3 weeks) to 0.16 μg Mn/kg/day (18 months), with the highest intakes at the youngest age stage we considered, 3 weeks. Estimated daily Mn intake from formula products reconstituted with 0 μg Mn/L water ranged from 130 μg Mn/kg/day (3 weeks) to 4.8 μg Mn/kg/day (18 months) with the highest intakes at 3 weeks. Formula products provided 28-520 times greater than the mean daily intake of Mn from breast milk for the 4 age stages that we considered. Estimated daily Mn intake from formula products reconstituted with water containing 250 μg Mn/L ranged from 12 μg Mn/kg/day to 170 μg Mn/kg/day, which exceeds the United States Environmental Protection Agency Reference Dose of 140 μg Mn/kg/day for adults., Conclusions: Mn deficiency is highly unlikely with exclusive breast milk or infant formula feeding, but established tolerable daily intake levels for Mn may be surpassed by some of these products when following labeled instructions., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Increased emergency medical services (EMS) response times and areas of low socioeconomic status are both associated with poorer outcomes for several time-sensitive medical conditions attended to by medical personnel before a patient is hospitalized. We evaluated the association between EMS response times, area deprivation level, and on-scene access constraints encountered by EMS in a large urban area in France. We conducted a multicenter prospective cohort study of EMS dispatches occurring in the forty-seven cities in a region southeast of Paris. We fit multilevel mixed-effects linear regression models for multivariate assessment of the predictors of EMS response times and then used multivariate logistic regression on outcomes among a subgroup of patients presenting with out-of-hospital cardiac arrest. We found evidence that access constraints were more frequently encountered by EMS in the most deprived areas compared to less deprived ones, and were associated with increased EMS response times until patient contact and with poorer outcomes from cardiac arrest. Strategies to anticipate and overcome access constraints should be implemented to improve outcomes for emergent conditions attended to by prehospital medical teams.

Background: The pathophysiology of the leading cause of pediatric acute nephritis, acute postinfectious GN, including mechanisms of the pathognomonic transient complement activation, remains uncertain. It shares clinicopathologic features with C3 glomerulopathy, a complement-mediated glomerulopathy that, unlike acute postinfectious GN, has a poor prognosis., Methods: This retrospective study investigated mechanisms of complement activation in 34 children with acute postinfectious GN and low C3 level at onset. We screened a panel of anticomplement protein autoantibodies, carried out related functional characterization, and compared results with those of 60 children from the National French Registry who had C3 glomerulopathy and persistent hypocomplementemia., Results: All children with acute postinfectious GN had activation of the alternative pathway of the complement system. At onset, autoantibodies targeting factor B (a component of the alternative pathway C3 convertase) were found in a significantly higher proportion of children with the disorder versus children with hypocomplementemic C3 glomerulopathy (31 of 34 [91%] versus 4 of 28 [14%], respectively). In acute postinfectious GN, anti-factor B autoantibodies were transient and correlated with plasma C3 and soluble C5b-9 levels. We demonstrated that anti-factor B antibodies enhance alternative pathway convertase activity in vitro , confirming their pathogenic effect. We also identified crucial antibody binding sites on factor B, including one correlated to disease severity., Conclusions: These findings elucidate the pathophysiologic mechanisms underlying acute postinfectious GN by identifying anti-factor B autoantibodies as contributing factors in alternative complement pathway activation. At onset of a nephritic syndrome with low C3 level, screening for anti-factor B antibodies might help guide indications for kidney biopsy to avoid misdiagnosed chronic glomerulopathy, such as C3 glomerulopathy, and to help determine therapy., (Copyright © 2020 by the American Society of Nephrology.)

Background: Non-participation and attrition are rarely studied despite being important methodological issues when performing post-disaster studies. A longitudinal survey of civilians exposed to the January 2015 terrorist attacks in Paris, France, was conducted 6 (Wave 1) and 18 months (Wave 2) after the attacks. We described non-participation in Wave 1 and determined the factors associated with attrition in Wave 2., Methods: Multivariate logistic regression models were used to compare participants in both waves with those who participated in the first wave only. Analyses were performed taking the following factors into account: socio-demographic characteristics, exposure to terror, peri-traumatic reactions, psychological support, perceived social support, impact on work, social and family life, and mental health disorders. Characteristics of new participants in Wave 2 were compared with participants in both waves using a chi-square test., Results: Of the 390 persons who were eligible to participate in the survey, 190 participated in Wave 1 (participation rate: 49%). The most frequently reported reason for non-participation was to avoid being reminded of the painful event (32%, n = 34/105). In Wave 2, 67 were lost to follow-up, 141 people participated, of whom 123 participated in Wave 1 (re-participation rate: 65%) and 18 were new. Attrition in Wave 2 was associated with socio-demographic characteristics (age, French origin) and location during the attacks, but not with terror exposure or mental health disorders. Compared with those who participated in both waves, new participants declared less social and psychological support since the attacks., Conclusions: Attrition at 6 months was not associated with exposure to terror or mental health disorders, which indicates that any bias in future analyses on IMPACTS on mental health outcomes will be limited. Our findings suggest the importance of adapting similar surveys for people of foreign origin and of improving strategies to avoid attrition of younger people, for example by using social media, peers, and the educational environment. The present study also revealed that a high level of exposure to terror and a lack of social and psychological support after a terrorist event could impede individuals' participation in similar surveys in the short term.

The history of phrenology in France has a number of unique features. It was in that country that F. J. Gall sought refuge; and it was, above all, in France that phrenology would subsequently attempt to establish its credentials as a new physiological science of the mind. Up until the 1840s, phrenology expanded rapidly in the country, a growth that coincided with attempts to provide this new field with the trappings of respectable scientific endeavor-courses of lectures, learned societies, journals, and so on. This ambitious intellectual project, despite its controversial nature, made a major cultural impact in the nineteenth century, both through its influence on the written word-from learned journals to the novel-and via its striking visual imagery (sculpture, anatomical diagrams and models, engravings, caricatures, and so on). However, as the scientific impact of phrenology declined, allusions to it lost much of their cultural force. On the borderline between respectable science and mere quackery, phrenology in France represented an attempt to construct a whole new intellectual universe based on scientific principles, and as such had a profound impact on its period.

Exposure to high levels of manganese (Mn) in children has recently been associated with adverse neurodevelopmental effects. Current infant formula regulations for Mn content were set between 1981 (United States), 2006 (European Union, France), and 2007 (Codex Alimentarius) prior to the publication of much of the growing body of research on the developmental neurotoxicity of Mn. In this study, we sought to measure the concentrations of Mn in some infant formulas and young child nutritional beverages available on the United States (US) and French markets using ion beam analysis by particle induced X-ray emission (PIXE) spectrometry and then compare the analytical results to concentrations reported in the literature for breast milk and applicable infant formula regulations and guidelines. We were particularly interested in measuring Mn concentrations in product types for which there is very little data from previous surveys, especially soy-based, rice-based, goat-milk based, chocolate-flavored, and nutritional beverages for young children that are not regulated as infant or follow-on formulas (e.g. "toddler formulas" and "toddler powders"). We purchased 44 infant formulas and young child nutritional beverage products in the US and France with varying protein sources (cow-milk, goat-milk, soy, rice) labelled for birth to 3 years. We selected these samples using maximum variation sampling to explore market extremes to facilitate comparisons to regulatory limits. Since this sampling method is non-probabilistic, other inferences cannot be made beyond this set of samples to the overall markets. We used ion beam analysis to measure the concentrations of Mn in each product. The range of measured Mn concentrations in the products is 160-2,800 μg/L, substantially higher than the 3-6 μg/L mean Mn concentration reported in human breast milk. All products satisfied national and Codex Alimentarius Commission (CAC) international standards for minimum Mn content in infant formulas; however, 7/25 of the products purchased in the US exceeded the CAC Guidance Upper Level of 100 μg Mn/kcal for infant formula., Competing Interests: EJM’s affiliation is with Better Life Laboratories, a nonprofit organization that conducts scientific research and provides technical expertise, equipment, and training to help needy people around the world. Better Life Laboratories received no specific funding for this project from any donors. Donors to Better Life Laboratories provided no input in choosing the subject matter of this project, the hypotheses that were tested, the individual samples that were analyzed, the method of analysis, the research findings, or the manner of disseminating the results. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care., Methods: We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with ClinicalTrials.gov, NCT02149589., Findings: From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61-1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p<0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5-5·1; p=0·012., Interpretation: Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial., Funding: French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The question of whether exposure to bisphenol A (BPA) contributes to the development of type 2 diabetes is still unresolved. Most epidemiological evidence on the association between BPA and diabetes is from cross-sectional studies or longitudinal studies with single urinary measurements. No prospective study has examined exposure to BPA analogs such as bisphenol S (BPS) in relation to incident type 2 diabetes., Objectives: We aimed to investigate whether exposure to BPA and BPS, assessed at up to two time points, was associated with the incidence of type 2 diabetes., Methods: We performed a case-cohort study on 755 participants without diabetes at baseline and followed-up over 9 y as part of the French prospective cohort Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.). BPA-glucuronide (BPA-G) and BPS-glucuronide (BPS-G) were assessed in fasting spot urine samples collected during the health examinations at baseline and 3 y later. Associations with incident diabetes were examined using Prentice-weighted Cox regression models adjusted for potential confounders., Results: A total of 201 incident cases of type 2 diabetes were diagnosed over the follow-up, including 30 in the subcohort. Compared with participants with the lowest average BPA exposure (below the first quartile), participants in the second, third, and fourth quartile groups of exposure had a near doubling of the risk of type 2 diabetes, with a hazard ratio ( HR )   = 2.56 (95% CI: 1.16, 5.65), 2.35 (95% CI: 1.07, 5.15), and 1.56 (95% CI: 0.68, 3.55), respectively. The detection of BPS-G in urine at one or both time points was associated with incident diabetes, with an HR   = 2.81 (95% CI: 1.74, 4.53)., Discussion: This study shows positive associations between exposure to BPA and BPS and the incidence of type 2 diabetes, independent of traditional diabetes risk factors. Our results should be confirmed by recent, population-based observational studies in different populations and settings. Overall, these findings raise concerns about using BPS as a BPA substitute. Further research on BPA analogs is warranted. https://doi.org/10.1289/EHP5159.

Background: Psychiatric care is a fruitful setting for exploring the rise of surveillance medicine, which shapes gray zones of uncertainty between health and illness. Predicting psychosis has become a priority in the international mental health field, but French psychiatrists appear reluctant to refer their young patients for standardized assessments or disclose their risks to them., Aim: This research addressed French psychiatrists' attitudes towards risk disclosure about psychosis to adolescents presenting symptoms that might reflect either typical teenager unease or the first signs of psychosis onset., Methods: A mixed-method design included 12 in-depth qualitative interviews followed by an online survey with responses from 487 psychiatrists., Results: French psychiatrists' reluctance to engage in risk disclosure emerges from a professional norm: a belief in the self-fulfilling prophecy. They - especially those with a background in social science and psychology - believe in the optimistic self-fulfilling prophecy. They fear the consequences of pessimistic predictions, struggle to maintain functional optimism, favor long-term inconspicuous medical watchfulness, and systematically understand favorable outcomes as a consequence of medical care, independent of the accuracy of risk detection., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort., Methods: We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458., Findings: Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27)., Interpretation: Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection., Funding: INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The REHABase project is a French observational, prospective, and multicenter cohort study of serious mental illness and autism spectrum disorder (ASD), launched in 2016 for a planned minimum duration of 15 years. The aim is to characterize the care and quality-of-life needs of participants. This article presents initial results from data collection., Methods: Psychosocial, cognitive, and functional data were collected at baseline, annually, and after rehabilitation care. Data from the baseline evaluation on diagnoses, medications, well-being, insight, life satisfaction, and care needs are presented. The clinical profiles of REHABase participants with serious mental illness or ASD were assessed in relation to their level of satisfaction with life and well-being in nine life dimensions and their needs, according to their stage of recovery in a five-stage model., Results: Baseline data were collected for 1,397 participants between January 2016 and August 2018. Main diagnoses were schizophrenia spectrum disorder (49%); ASD (13%); and personality (12%), bipolar (9%), and major depressive (6%) disorders. More than 50% of participants reported needs for care or interventions in four of nine dimensions: employment, cognitive functioning, symptom management, and interpersonal relationships. Nearly half of participants were not in the active stages of recovery (stages 4 and 5), and even those considered to have reached the final stage continued to require help in several areas., Conclusions: Most participants had already received psychiatric care for several years, and most remained dissatisfied with their social and emotional life and their psychological well-being.

Background: The use of pesticides can affect non-target species by causing population declines through indirect intoxication. Small mustelids (SMs; weasels, Mustela nivalis L.; stoats, Mustela erminea L.) consume water voles (WVs, Arvicola scherman S.) and can be exposed to bromadiolone, an anticoagulant rodenticide used in some countries to reduce WV damage to grasslands. Here, we investigated whether bromadiolone affected SM abundance., Results: We monitored SM abundance using footprint tracking tunnels in spring and autumn at ten sites. Among these sites, four were treated with bromadiolone, while six were not treated. We found reduced SM abundance at these four sites from spring to autumn (treated sites, mean ± SE SM abundance change = -1.68 ± 0.42; untreated sites, 0.29 ± 0.25). Using a linear model, we observed that SM abundance decreased as a function of the quantity of bromadiolone applied during the 3 months before the autumn estimate. We found that WV abundance increased at treated sites (linear model, treated sites, mean ± SE WV abundance change = 1.4 ± 0.4; untreated sites, 0.33 ± 0.25). Thus, at treated sites, SM abundance declined despite increased food availability. By analyzing residues in vole livers and SM scats we showed that SMs may be exposed to bromadiolone at the sites where this compound was used., Conclusion: This study is the first to document the relationship between SM abundance and bromadiolone usage for small mammal control. Declines in SM abundance were observed at treated sites, where bromadiolone residue was found in SM scats. This correlative approach suggests that bromadiolone treatment may lead to seasonal SM declines and associated WV increases. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Biogeochemical reactions occur unevenly in space and time, but this heterogeneity is often simplified as a linear average due to sparse data, especially in subsurface environments where access is limited. For example, little is known about the spatial variability of groundwater denitrification, an important process in removing nitrate originating from agriculture and land use conversion. Information about the rate, arrangement, and extent of denitrification is needed to determine sustainable limits of human activity and to predict recovery time frames. Here, we developed and validated a method for inferring the spatial organization of sequential biogeochemical reactions in an aquifer in France. We applied it to five other aquifers in different geological settings located in the United States and compared results among 44 locations across the six aquifers to assess the generality of reactivity trends. Of the sampling locations, 79% showed pronounced increases of reactivity with depth. This suggests that previous estimates of denitrification have underestimated the capacity of deep aquifers to remove nitrate, while overestimating nitrate removal in shallow flow paths. Oxygen and nitrate reduction likely increases with depth because there is relatively little organic carbon in agricultural soils and because excess nitrate input has depleted solid phase electron donors near the surface. Our findings explain the long-standing conundrum of why apparent reaction rates of oxygen in aquifers are typically smaller than those of nitrate, which is energetically less favorable. This stratified reactivity framework is promising for mapping vertical reactivity trends in aquifers, generating new understanding of subsurface ecosystems and their capacity to remove contaminants., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Vowel harmony is a linguistic phenomenon whereby vowels within a word share one or several of their phonological features, constituting a nonadjacent, and thus challenging, dependency to learn. It can be found in a large number of agglutinating languages, such as Hungarian and Turkish, and it may apply both at the lexical level (i.e., within word stems) and at the morphological level (i.e., between stems and their affixes). Thus, it might affect both lexical and morphological development in infants whose native language has vowel harmony. The current study asked at what age infants learning an irregular harmonic language, Hungarian, become sensitive to vowel harmony within word stems. In a head-turn preference study, 13-month-old, but not 10-month-old, Hungarian-learning infants preferred listening to nonharmonic VCV (vowel-consonant-vowel) pseudowords over vowel-harmonic ones. A control experiment with 13-month-olds exposed to French, a nonharmonic language, showed no listening preference for either of the sequences, suggesting that this finding cannot be explained by a universal preference for nonharmonic sequences but rather reflects language-specific knowledge emerging between 10 and 13 months of age. We discuss the implications of this finding for morphological and lexical learning., (Copyright © 2018. Published by Elsevier Inc.)

Background: The placenta performs crucial physiological functions to ensure normal fetal development. Few epidemiological studies investigated placental weight sensitivity to phthalates and phenols., Objective: Our goal was to explore whether maternal exposure to select phthalates and phenols is associated with changes in placental weight at birth and in placental–to–birth weight ratio (PFR)., Methods: Placental weight and birth weight were available for 473 mother–son pairs in the EDEN (Etude des Déterminants pré et postnatals du développement et de la santé de l'Enfant) cohort for whom 9 phenols (4 parabens, 2 dichlorophenols, triclosan, benzophenone-3, bisphenol A) and 11 phthalate metabolites were measured in spot urine samples collected between weeks 23 and 29 of gestation. We used adjusted Elastic Net penalized regression models (ENET) to select biomarkers associated with placental weight, birth weight and PFR. Unpenalized effect estimates were then obtained by fitting linear regression models simultaneously adjusted for the ENET-selected biomarkers and a priori chosen confounders., Results: The multipollutant ENET model for placental weight retained four biomarkers: triclosan and monocarboxy-isononyl phthalate (MCNP), which were negatively associated with placental weight, and benzophenone-3 and the sum of parabens, which were positively associated with this outcome. The ENET model for PFR retained two phthalate metabolites [MCNP and monocarboxy-isooctyl phthalate (MCOP)], which were negatively associated with this outcome., Discussion: The positive association between the sum of parabens and placental weight was consistent with results of a previous study among 49 male births. Our results provide preliminary evidence of possible associations between other compounds such as triclosan, benzophenone-3, MCNP, and MCOP and both placental weight and PFR. These associations were not reported in previous studies and should be seen as hypothesis generating. Studies relying on repeated assessments of exposure in prospective mother–child cohorts are needed to substantiate the plausibility of the hypotheses generated by our results. https://doi.org/10.1289/EHP3523.

In this article, we analyze qualitatively the understanding of and reactions to personalized nutrition (PN) among the French public. Focus groups were conducted to identify the opinions and discourses about two applications of knowledge from nutritional (epi)genomics: a biotechnology (nutrigenetic testing) and a public awareness campaign (the "first thousand days of life" initiative). Our objective was to understand to what extent PN could lead to changes in eating practices as well as in the representations of food-health relationships within France, a country characterized by a strong commitment to commensality and a certain "nutritional relativism." Although discourses on nutritional genomics testify to a resistance to food medicalization, nutritional epigenomics appears as more performative because it introduces the question of transgenerational transmission, thus parental responsibility.

Background: Enteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR., Methods: We did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens., Findings: Between June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 [99%] of 71 vs 62 [87%] of 71; p=0·011) and infants (76 [92%] of 83 vs 62 [75%] of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 [55%] of 163 vs 148 [91%] of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 [100%] of 55 vs 41 [75%] of 55; p=0·0002) or with sepsis-like disease (16 [100%] of 16 vs nine [56%] of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 [67%] of 246 vs 222 [90%] of 246; p<0·0001)., Interpretation: Testing for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness., Funding: University Hospital Clermont-Ferrand., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Digital spaces, and in particular social networking sites, are becoming increasingly present and influential in the functioning of our democracies. In this paper, we propose an integrated methodology for the data collection, the reconstruction, the analysis and the visualization of the development of a country's political landscape from Twitter data., Method: The proposed method relies solely on the interactions between Twitter accounts and is independent of the characteristics of the shared contents such as the language of the tweets. We validate our methodology on a case study on the 2017 French presidential election (60 million Twitter exchanges between more than 2.4 million users) via two independent methods: the comparison between our automated political categorization and a human categorization based on the evaluation of a sample of 5000 profiles descriptions; the correspondence between the reconfigurations detected in the reconstructed political landscape and key political events reported in the media. This latter validation demonstrated the ability of our approach to accurately reflect the reconfigurations at play in the off-line political scene., Results: We built on this reconstruction to give insights into the opinion dynamics and the reconfigurations of political communities at play during a presidential election. First, we propose a quantitative description and analysis of the political engagement of members of political communities. Second, we analyze the impact of political communities on information diffusion and in particular on their role in the fake news phenomena. We measure a differential echo chamber effect on the different types of political news (fake news, debunks, standard news) caused by the community structure and emphasize the importance of addressing the meso-structures of political networks in understanding the fake news phenomena., Conclusions: Giving access to an intermediate level, between sociological surveys in the field and large statistical studies (such as those conducted by national or international organizations) we demonstrate that social networks data make it possible to qualify and quantify the activity of political communities in a multi-polar political environment; as well as their temporal evolution and reconfiguration, their structure, their alliance strategies and their semantic particularities during a presidential campaign through the analysis of their digital traces. We conclude this paper with a comment on the political and ethical implications of the use of social networks data in politics. We stress the importance of developing social macroscopes that will enable citizens to better understand how they collectively make society and propose as example the "Politoscope", a macroscope that delivers some of our results in an interactive way., Competing Interests: The authors have declared that no competing interests exist.

Recommendations on the glomerular filtration rate (GFR) threshold compatible with living kidney donation are not agreed upon. The recent KDIGO guidelines suggested a reset of the conventional cutoff value of 80 to 90 mL/min/1.73 m 2 . While GFR physiologically declines with age, it is unclear whether and how age should be taken into account for selecting acceptable pre-donation GFR. In this multicenter retrospective study encompassing 2007 kidney donors in France, we evaluated the impact of age using two threshold measured GFR (mGFR)s (80 and 90 mL/min/1.73 m 2 ). Three groups of donors were defined according to baseline mGFR: below 80, 80-89.9 and 90 mL/min/1.73 m 2 or more. Thirty-two percent of donors were selected despite an mGFR below 90 mL/min/1.73 m 2 . Donors with the lowest mGFR were significantly older (60 ± 9 vs. 47 ± 11 years) and this applied to both male and female donors. The lifetime-standardized renal reserve, defined as the pre-donation mGFR value divided by the expected number of remaining years of life, was similar irrespective of baseline mGFR groups. Similar results were obtained when eGFR was used instead of mGFR. Finally, in a subgroup of 132 donors with repeated mGFR five years after donation, the magnitude of mGFR decrease was similar in all groups (-34.3%, -33.9%, and -34.9% respectively). Thus, the decision to accept individuals with mGFR lower than 90 mL/min/1.73 m 2 for kidney donation is highly dependent on the age of the candidate. Hence, threshold values lower than 90 mL/min/1.73 m 2 are reasonable for older donors. Age-calibrated mGFR may improve efficiency of the selection process., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: The management of acute upper gastrointestinal bleeding (UGIB) is challenging in patients with cirrhosis, as it is responsible for severe complications and high mortality rates. Tranexamic acid (TXA) may help control the bleeding by counterbalancing cirrhosis-related hyperfibrinolysis. Still, there is a lack of unbiased data to conclude on its efficacy. The aim of this study is to evaluate the efficacy of TXA in the early treatment of acute UGIB in patients with cirrhosis., Methods and Analysis: This study is a multicentre, randomised, double-blind, placebo-controlled trial, for adult patients with cirrhosis presenting with an acute UGIB and allocated to one of two arms: TXA or placebo (saline). Physicians from emergency mobile services, emergency departments (EDs) or intensive care units (ICUs) can include patients. Besides study intervention, standard care for UGIB will be performed as recommended. Intervention will consist an intravenous infusion of 10 mL of TXA (1 g) or saline, immediately followed by three identical intravenous infusions over 8 hours each (total dose of 4 g of TXA or 40 mL of placebo over 24 hours). Main analyses will be conducted in intention to treat on every patient included, then in modified intention to treat on patients with underlying lesion of portal hypertension visualised by endoscopy. The main objective is to show efficacy of TXA until day 5 on a composite criterion (bleeding control, rebleeding episodes and mortality). Secondary objectives aim at showing the efficacy of TXA on each individual component of the main outcome measure and others at 6 weeks and later (transjugular intrahepatic portosystemic shunt procedure, cirrhosis-specific complications, length of stay in ICU and in hospital, safety and tolerance of TXA, liver transplantation). Included patients will be followed up to 1 year after inclusion.500 patients will be necessary to show a reduction in the prevalence of the primary outcome from 30% to 18% with a bilateral alpha risk of 5% and a power of 80%., Ethics and Dissemination: Ethical approval has been obtained from the Comité de Protection des Personnes Ile-de-France 1 (CPP-IDF1). Results will be disseminated via publications in peer-review medical journals and scientific forums., Protocol Version: This protocol is based on the latest version, as established on 11 October 2017 and validated by the IRB CPP Ile-de-France 1., Trial Registration Number: NCT03023189., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Organic market gardening is often promoted by urban municipalities as a way to resource part of the food supply, creating new social links and protecting groundwater resources. The agronomical and environmental performance of six commercial organic market gardening farms supplying vegetables in Paris were evaluated and compared with other vegetable production systems. When expressed in terms of protein production, the yield of these systems appears rather low compared with the productive capacity of open-field organic cropping systems where vegetable production is inserted into rotation with other crops. Moreover, the requirement of producing infiltrated water meeting the drinking water standards seriously limits the allowable rate of fertilisation, thus limiting production. The data reported herein show that to supply the amount of vegetables required by the Paris agglomeration (12 million inhabitants) only by organic market gardening, 160,000-205,000 ha, i.e. 28-36 % of the agricultural area of the surrounding Ile-de-France region, would be required. We conclude that organic market gardening is only one of several other farming systems which can contribute to a re-localised supply of vegetables to large cities.

Objectives: To compare the association between a restrictive transfusion strategy and cardiovascular complications during hospitalization for hip fracture with the association between a liberal transfusion strategy and cardiovascular complications, accounting for all transfusions from the emergency department to postacute rehabilitation settings., Design: Retrospective study., Setting: Perioperative geriatric care unit., Participants: All individuals aged 70 and older admitted to the emergency department for hip fracture and hospitalized in our perioperative geriatric care unit (N=667; n=193 in the liberal transfusion group, n=474 in the restrictive transfusion group) from July 2009 to April 2016., Intervention: A restrictive transfusion strategy (hemoglobin level threshold ≥8 g/dL or symptoms) used from January 2012 to April 2016 was compared with the liberal transfusion strategy (hemoglobin level threshold ≥10 g/dL) used from July 2009 to December 2011., Measurements: Primary endpoint was in-hospital acute cardiovascular complications (heart failure, myocardial infarction, atrial fibrillation or stroke)., Results: The change to a restrictive transfusion strategy was associated with fewer acute cardiovascular complications (odds ratio=0.45, 95% confidence interval (CI)=0.31-0.67, p<.001), without any noticeable difference in in-hospital or 6-month mortality. The change also led to a reduction in packed red blood cell units used per participant (median 1, interquartile range (IQR) 0-2 in restrictive vs median 2, IQR 0-3 in liberal transfusion strategy, P<.001). In rehabilitation settings, the frequency of transfusion was greater with the restrictive transfusion strategy than the liberal transfusion strategy (18% vs 9%, P<.001)., Conclusion: A restrictive transfusion strategy in older adults with hip fracture was found to be safe and was associated with fewer cardiovascular complications but more transfusions in rehabilitation settings. Prospective studies are needed to confirm these findings., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Background: Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone., Methods: We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only., Findings: Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p<0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p<0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide., Interpretation: In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications., Funding: German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Telangiectasia macularis eruptiva perstans (TMEP) has not been fully characterized., Objective: We sought to estimate the frequency and clinical characteristics of TMEP in a cohort of adult patients with cutaneous mastocytosis, and to assess the presence of systemic involvement., Methods: We included all consecutive patients evaluated for cutaneous mastocytosis in 2 centers: the Mastocytosis Competence Center of the Midi-Pyrénées from May 2006 to December 2013, and the French Reference Center for Mastocytosis from January 2008 to September 2013. Skin phenotype, histopathology, presence of KIT mutation in the skin, and assessment of systemic involvement according to World Health Organization (WHO) criteria were prospectively investigated., Results: Of 243 patients with cutaneous mastocytosis, 34 (14%) were given a diagnosis of TMEP. The diagnosis of systemic mastocytosis was established in 16 patients (47%) with TMEP. Three patients (9%) had aggressive systemic mastocytosis (C-findings according to WHO). In all, 32 patients (94%) exhibited at least 1 mast cell activation-related symptom., Limitations: Patient recruitment was undertaken at 2 referral centers with expertise in the diagnosis and treatment of mastocytosis so that the clinical findings and incidence of systemic involvement may be overestimated in comparison with the overall population of patients with TMEP., Conclusion: TMEP accounts for about 14% of patients with cutaneous mastocytosis. The disease manifests as mast cell activation symptoms in almost all patients and can be associated with systemic involvement in about 50% of cases., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of the study was to update the description of Li-Fraumeni syndrome (LFS), a remarkable cancer predisposition characterized by extensive clinical heterogeneity., Patients and Methods: From 1,730 French patients suggestive of LFS, we identified 415 mutation carriers in 214 families harboring 133 distinct TP53 alterations and updated their clinical presentation., Results: The 322 affected carriers developed 552 tumors, and 43% had developed multiple malignancies. The mean age of first tumor onset was 24.9 years, 41% having developed a tumor by age 18. In childhood, the LFS tumor spectrum was characterized by osteosarcomas, adrenocortical carcinomas (ACC), CNS tumors, and soft tissue sarcomas (STS) observed in 30%, 27%, 26%, and 23% of the patients, respectively. In adults, the tumor distribution was characterized by the predominance of breast carcinomas observed in 79% of the females, and STS observed in 27% of the patients. The TP53 mutation detection rate in children presenting with ACC or choroid plexus carcinomas, and in females with breast cancer before age 31 years, without additional features indicative of LFS, was 45%, 42% and 6%, respectively. The mean age of tumor onset was statistically different (P < .05) between carriers harboring dominant-negative missense mutations (21.3 years) and those with all types of loss of function mutations (28.5 years) or genomic rearrangements (35.8 years). Affected children, except those with ACC, harbored mostly dominant-negative missense mutations., Conclusion: The clinical gradient of the germline TP53 mutations, which should be validated by other studies, suggests that it might be appropriate to stratify the clinical management of LFS according to the class of the mutation., (© 2015 by American Society of Clinical Oncology.)

The first evidence of the partial infant Neandertal skeleton La Ferrassie 8 (LF8) was discovered in 1970, although most of the remains were found in 1973 as part of the 1968-1973 work at the site by H. Delporte. This individual and the other Neandertal children from La Ferrassie were published in the early 1980s by J.-L. Heim, and since then LF8 has been regarded as coming from a poorly documented excavation. The recent rediscovery of the box that contained the hominin bones given by Delporte to Heim in the Muséum national d'Histoire naturelle (MNHN) collection provided new fossils and helped to locate LF8 in the site: level M2 in square 1. Two visits to the Musée d'Archéologie nationale et Domaine national de Saint-Germain-en-Laye (MAN) yielded additional fossil remains from both the 1970 and 1973 excavations and resulted in the discovery of all of the notes from the excavation of H. Delporte between 1968 and 1973. Here the new fossil remains (47 after performing all possible refits), representing significant portions of the cranium, mandible, and vertebral column together with fragmentary hand and costal remains, are described. Unsurprisingly, the morphology of the bony labyrinth and of a complete stapes from the nearly complete left temporal show clear Neandertal affinities. Additionally, a complete reassessment of the original LF8 collection has resulted in the identification of several errors in the anatomical determination. Despite the significant increase in the anatomical representation of LF8, the skeletal remains are still limited to the head, thorax, pelvis, and four hand phalanges, with some very fragile elements relatively well preserved. Different hypotheses are proposed to explain this anatomical representation, which can be tested during future fieldwork., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Thyroid-stimulating hormone (TSH) is composed of a specific β subunit and an α subunit that is shared with the two pituitary gonadotropins. The three β subunits derive from a common ancestral gene through two genome duplications (1R and 2R) that took place before the radiation of vertebrates. Analysis of genomic data from phylogenetically relevant species allowed us to identify an additional Tshβ subunit-related gene that was generated through 2R. This gene, named Tshβ2, present in cartilaginous fish, little skate and elephant shark, and in early lobe-finned fish, coelacanth and lungfish, was lost in ray-finned fish and tetrapods. The absence of a second type of TSH receptor (Tshr) gene in these species suggests that both TSHs act through the same receptor. A novel Tshβ sister gene, named Tshβ3, was generated through the third genomic duplication (3R) that occurred early in the teleost lineage. Tshβ3 is present in most teleost groups but was lostin tedraodontiforms. The 3R also generated a second Tshr, named Tshrb. Interestingly, the new Tshrb was translocated from its original chromosomic position after the emergence of eels and was then maintained in its new position. Tshrb was lost in tetraodontiforms and in ostariophysians including zebrafish although the latter species have two TSHs, suggesting that TSHRb may be dispensable. The tissue distribution of duplicated Tshβs and Tshrs was studied in the European eel. The endocrine thyrotropic function in the eel would be essentially mediated by the classical Tshβ and Tshra, which are mainly expressed in the pituitary and thyroid, respectively. Tshβ3 and Tshrb showed a similar distribution pattern in the brain, pituitary, ovary and adipose tissue, suggesting a possible paracrine/autocrine mode of action in these non-thyroidal tissues. Further studies will be needed to determine the binding specificity of the two receptors and how these two TSH systems are interrelated.

Despite numerous sites of great antiquity having been excavated since the end of the 19th century, Middle Pleistocene human fossils are still extremely rare in northwestern Europe. Apart from the two partial crania from Biache-Saint-Vaast in northern France, all known human fossils from this period have been found from ten sites in either Germany or England. Here we report the discovery of three long bones from the same left upper limb discovered at the open-air site of Tourville-la-Rivière in the Seine Valley of northern France. New U-series and combined US-ESR dating on animal teeth produced an age range for the site of 183 to 236 ka. In combination with paleoecological indicators, they indicate an age toward the end of MIS 7. The human remains from Tourville-la-Rivière are attributable to the Neandertal lineage based on morphological and metric analyses. An abnormal crest on the left humerus represents a deltoid muscle enthesis. Micro- and or macro-traumas connected to repetitive movements similar to those documented for professional throwing athletes could be origin of abnormality.

Microscopical and molecular analyses were used to investigate the diversity and spatial community structure of spring phytoplankton all along the estuarine gradient in a macrotidal ecosystem, the Baie des Veys (eastern English Channel). Taxa distribution at high tide in the water column appeared to be mainly driven by the tidal force which superimposed on the natural salinity gradient, resulting in a two-layer flow within the channel. Lowest taxa richness and abundance were found in the bay where Teleaulax-like cryptophytes dominated. A shift in species composition occurred towards the mouth of the river, with the diatom Asterionellopsis glacialis dramatically accumulating in the bottom waters of the upstream brackish reach. Small thalassiosiroid diatoms dominated the upper layer river community, where taxa richness was higher. Through the construction of partial 18S rDNA clone libraries, the microeukaryotic diversity was further explored for three samples selected along the surface salinity gradient (freshwater - brackish - marine). Clone libraries revealed a high diversity among heterotrophic and/or small-sized protists which were undetected by microscopy. Among them, a rich variety of Chrysophyceae and other lineages (e.g. novel marine stramenopiles) are reported here for the first time in this transition area. However, conventional microscopy remains more efficient in revealing the high diversity of phototrophic taxa, low in abundances but morphologically distinct, that is overlooked by the molecular approach. The differences between microscopical and molecular analyses and their limitations are discussed here, pointing out the complementarities of both approaches, for a thorough phytoplankton community description.

The Afrotropical Belostomatidae fauna has long proved to be a difficult taxonomic problem, not so much for the overwhelmingly large number of species involved but rather because of a lack of trained specialists. The rarity of some taxa also contributes to confusion, because some species remain poorly described or are known only from one or two specimens. During a visit to the Muséum National d'Histoire Naturelle, Paris, France and the Musée Royal de l'Afrique Centrale, Tervuren, Belgium, it was possible to comprehensively review the Limnogeton species based mainly on the specimens housed in the aforementioned collections. An updated key to adults of all species presently included in the genus, particularly based on male genitalia characters studied during the present study, has been provided.

In high-altitude summer pastures, horseflies (Diptera: Tabanidae) can be a serious nuisance to livestock, as well as mechanical vectors of animal diseases such as besnoitiosis, an enzootic disease in the Pyrenees. However, the activity of horseflies in mountainous environments is poorly documented. To study the seasonality and distribution of tabanids in the Pyrenees Mountains, a sampling design was set up in two valleys on opposite sides of the mountain, one north-facing and one south-facing, along high-elevation gradients and at different distances from a water body between May and October 2011. The influence of the landscape on species richness and abundance was assessed by taking into account forested and unforested areas in 200 m radii around the trapping sites. Our findings indicated that: (1) The slope, the altitude and the size of unforested patches significantly influenced community composition of tabanids. (2) Altitude had a positive or a negative effect, depending on the species. (3) Species richness and abundance were negatively correlated with large open habitats and positively correlated with patch-shape complexity. (4) Seasonal succession of the most abundant species was observed in both valleys, with a maximum of catches at the beginning of August; however, tabanid activity ended earlier in the southern valley, which was more exposed to sunlight. (5) Philipomyia aprica, Tabanus bromius, Tabanus glaucopis and Hybomitra auripila were active from 9:00 to 19:00 h (GMT+1), with a peak of activity at midday. This paper also discusses the implications of these findings in relation to changes in horsefly distribution and their control in mountainous environments.

The bouffia Bonneval at La Chapelle-aux-Saints is well known for the discovery of the first secure Neandertal burial in the early 20th century. However, the intentionality of the burial remains an issue of some debate. Here, we present the results of a 12-y fieldwork project, along with a taphonomic analysis of the human remains, designed to assess the funerary context of the La Chapelle-aux-Saints Neandertal. We have established the anthropogenic nature of the burial pit and underlined the taphonomic evidence of a rapid burial of the body. These multiple lines of evidence support the hypothesis of an intentional burial. Finally, the discovery of skeletal elements belonging to the original La Chapelle aux Saints 1 individual, two additional young individuals, and a second adult in the bouffia Bonneval highlights a more complex site-formation history than previously proposed.

During toxic spring and fall blooms produced by the dinoflagellate Alexandrium in the Thau lagoon (Mediterranean Sea), we monitored the presence of Amoebophryidae (Syndiniales), a group of parasites virulent toward a wide range of dinoflagellate hosts. A PCR-biased approach unveiled the presence of at least 10 different parasitic groups during Alexandrium proliferation. However, fluorescent in situ hybridization failed to reveal parasitic infection inside Alexandrium cells in field populations. In contrast, several co-occurring, less abundant thecate dinoflagellate species were infected by Amoebophryidae, showing up to 10% of infected cells. We concluded that Alexandrium populations were not infected by these local parasites, at least during our survey. In order to check this resistance capacity on a more global scale, we cross-infected several Alexandrium strains isolated from the Thau lagoon with one strain of the parasite Amoebophrya sp. originating from Salt Pond, MA, USA. All of these hosts were strongly infected by the North American parasite, leading to the conclusion that blooming Alexandrium in the Thau lagoon were not particularly resistant to this kind of parasite. These results provide additional evidence that dinoflagellates may become invasive when they successfully escaped their natural enemies in time and/or space (the "enemy release" hypothesis)., (Copyright © 2011 Institut Pasteur. All rights reserved.)

Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 13 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-Asparaginase-based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (61%), and only 4 of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia, and allergy. The absence of antiasparaginase antibodies and the disappearance of Epstein-Barr virus serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase-containing regimens in extranodal NK/T-cell lymphoma. L-Asparaginase-based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at www.clinicaltrials.gov as #NCT00283985.