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International audience; The follow-up of the development of the premature baby is a major component of its clinical care since it has been shown that it can reveal a pathology. However, no method allowing an automated and continuous monitoring of this development has been proposed. Within the framework of the Digi-NewB European project, our team wishes to offer new clinical indices qualifying the maturation of newborns. In this study, we propose a new method to characterize motor activity from video recordings. For this purpose, we have chosen to characterize the motion temporal organization by drawing inspiration from sleep organization. Thus, we propose a fully automatic process allowing to extract motion features and to combine them to estimate a functional age. By investigating two datasets, one of 28.5 hours (manually annotated) from 33 newborns and one of 4,920 hours from 46 newborns, we show that the proposed approach is relevant for monitoring in clinical routine and that the extracted features reflect the maturation of preterm newborns. Indeed, a compact and interpretable model using gestational age and three motion features (mean duration of intervals with motion, total percentage of time spent in motion and number of intervals without motion) was designed to predict post-menstrual age of newborns and showed an admissible mean absolute error of 1.3 weeks. While the temporal organization of motion was not studied clinically due to a lack of technological means, these results open the door to new developments, new investigations and new knowledge on the evolution of motion in newborns.

International audience; Introduction: We aimed to describe patients with coexisting infective endocarditis (IE) and bacterial meningitis (BM).Methods: We merged two large prospective cohorts, an IE cohort and a BM cohort, with only cases of definite IE and community-acquired meningitis. We compared patients who had IE and BM concurrently to patients with IE only and BM only.Results: Among the 1030 included patients, we identified 42 patients with IE-BM (4.1%). Baseline characteristics of patients with IE-BM were mostly similar to those of patients with IE, but meningitis was the predominant presentation at admission (39/42, 92.3%). Causative pathogens were predominantly Streptococcus pneumoniae (18/42, 42.9%) and Staphylococcus aureus (14/42, 33.3%). All pneumococcal IE were associated with BM (18/18). BM due to oral and group D streptococci, Streptococcus agalactiae, and S. aureus were frequently associated with IE (14/30, 46.7%). Three-month mortality was 28.6% in patients with IE-BM, 20.5% in patients with IE, and 16.6% in patients with BM.Conclusions: Patients with pneumococcal IE or altered mental status during IE must be investigated for BM. Patients with S. aureus, oral and group D streptococcal or enterococcal BM, or unfavorable outcome in pneumococcal meningitis would benefit from an echocardiography. Patients with the dual infection have the worst prognosis. Their identification is mandatory to initiate appropriate treatment.

Trial registration: ClinicalTrial.Gov identification number NCT01730690. the COMBAT study group; International audience; Introduction: COMBAT is a prospective, multicentre cohort study that enrolled consecutive adults with community-acquired bacterial meningitis (CABM) in 69 participating centres in France between February 2013 and July 2015 and followed them for 1 year.Methods: Patients aged at least 18 years old, hospitalised with CABM were followed during their hospitalisation and then contacted by phone 12 months after enrolment. Here we present the prevalence of sequelae at 12 months in a subgroup of patients with meningococcal meningitis.Results: Five of the 111 patients with meningococcal meningitis died during initial hospitalisation and two died between discharge and 12 months, leaving 104 patients alive 1 year after enrolment, 71 of whom provided 12-month follow-up data. The median age was 30.0 years and 54.1% of the patients had no identified risk factor for meningitis. More than 30% reported persistent headache, more than 40% were not satisfied with their sleep and 10% had concentration difficulties. Hearing loss was present in about 15% of the patients and more than 30% had depressive symptoms. About 13% of the patients with a previous professional activity had not resumed work. On the SF-12 Health Survey, almost 50% and 30% had physical component or mental component scores lower than the 25th percentile of the score distribution in the French general population. There was a non-significant improvement in the patients' disability scores from hospital discharge to 12 months (p = 0.16), but about 10% of the patients had residual disability.Conclusions: Although most patients in our cohort survive meningococcal meningitis, the long-term burden is substantial and therefore it is important to ensure a prolonged follow-up of survivors and to promote preventive strategies, including vaccination.

Climate change mitigation is one of the main global challenges in the 21st century. In this context, the recent 26th United Nations Climate Change Conference of the Parties (COP26-Glasgow) claimed for searching urgent and efficient measures to reduce and ultimately avoid CO2 emissions. Thus, many efforts from the scientific community focus on the research of new and renewable energy sources (RES). Among other approaches, green hydrogen, which comes from water electrolysis, is a promising candidate to be considered in the energy panorama. However, commercial electrolyzers are provided with Pt/C and Ir-based electrocatalytic materials, which are expensive and not abundant, to catalyze the Hydrogen Evolution Reaction (HER) in safe, stable, inexpensive, and environmentaly friendly conditions. Thus, this work aims to synthesize high-performance and very low metal loading catalysts by immobilizing a Rh-based organometallic complex (RhCp*Cl(phendiamine)]Cl) on a carbon black support following a robust synthesis procedure. Advanced characterization of the synthesized materials confirmed that ultra-low metal loadings in the range of 3.2-4.7 mg·g-1 were successfully reached. Subsequently, Rh-based catalysts were tested in a PEM electrolyzer. For metal loadings as low as 0.0066 mg·cm-2 competitive cell potentials of 1.9V were achieved working with 0.5A·cm-2 geometric current density at 70°C. These results are comparable to those obtained with Pt-based commercial cathodes working under similar operation conditions. Thus, the results of this research make a step forward in the substitution of conventional cathodes for the electrolytic HER by new materials with very low metal loadings. The authors of this work would like to show their gratitude to the financial support from the European Regional Development Fund in the framework of the Interreg Atlantic program through the project “HYLANTIC”-EAPA_204/2016”. The Spanish Ministry of Science and Innovation has also supported this work through the project PLEC2021-007718.

International audience; L'ouvrage L'efficacité des dispositifs de lutte contre les atteintes à la probité aborde la question de la prévention et de la lutte contre les atteintes à la probité dans le secteur privé et public, dans ses aspects à la fois juridiques et institutionnels tout en permettant d’obtenir – via l’expérience des acteurs de cette lutte sur le territoire – un éclairage sur les spécificités que la question revêt en Outre-mer. Disposant d’un statut d’autonomie prévu dans la loi organique du 27 février 2004 qui lui confère une compétence de droit commun dans toutes les matières qui ne relèvent pas expressément de la compétence de l’État, la Polynésie française présente une singularité institutionnelle, territoriale et culturelle qui impacte grandement son économie et complique, semble-t-il, la fixation des frontières entre public et privé, national et international, individu et communauté.Réunissant universitaires, magistrats, élus, professionnels et membres d’autorités administratives, cet ouvrage se propose d’apporter plusieurs regards sur la question de la prévention et de la lutte contre les atteintes à la probité dans les secteurs privé et public — dans ses aspects à la fois juridiques et institutionnels— afin de bénéficier d’un éclairage sur les spécificités que la thématique revêt en Outre-mer.

International audience; New use cases and the need for quality control and imaging data sharing in health studies require the capacity to align them to reference terminologies. We are interested in mapping the local terminology used at our center to describe imaging procedures to reference terminologies for imaging procedures (RadLex Playbook and LOINC/RSNA Radiology Playbook). We performed a manual mapping of the 200 most frequent imaging report titles at our center (i.e. 73.2% of all imaging exams). The mapping method was based only on information explicitly stated in the titles. The results showed 57.5% and 68.8% of exact mapping to the RadLex and LOINC/RSNA Radiology Playbooks, respectively. We identified the reasons for the mapping failure and analyzed the issues encountered.

International audience; Dispersal is a determining step in the life cycle of insects and a key factor of their energy budget. If the body stores of terrestrial insects are relatively well-documented, those of merolimnic insects (i.e., with aquatic larvae and terrestrial winged adults) remain poorly investigated. We assayed the body stores (protein, carbohydrate and lipid contents) of 18 families of merolimnic insects, encompassing a wide diversity of biological and ecological traits. We highlighted allometry between body stores and mass. The proportion of triglyceride and free carbohydrate relatively decreases with an increase in absolute insect mass, whereas protein and glycogen contents are proportional. We found a significant effect of insect order, Diptera having relatively more proteins than Trichoptera. For swarming taxa, males have relatively more triglycerides than their conspecific female. Passive dispersers are characterised by higher protein and glycogen contents Each body store was associated with specific life-history traits, emphasising the importance of considering each body store independently to better understand the associated functions. Dispersal strategies seem to be the main structuring factor underlying body store patterns of merolimnic insects, being significantly associated with the variation in adjusted triglycerides (30%), proteins (21%), glycogen (29%) and free carbohydrates (17%). However, our study estimated the role of flight only indirectly through the biological traits of insects. Future works should focus on identifying which substrates are used for flight, by comparing the proportion of body stores before and after flight, as well as protein identification to distinguish proteins associated with flight or reproduction. These further studies will help researchers in understanding the link between body stores of emerging merolimnic insects and the various facets of their ecology.

International audience; Urbanisation is known to change biodiversity patterns and plant-animal interactions such as pollination - a key ecological process. Floral traits like colour, size or UV-patterns are essential attractors for many pollinators. It is largely unknown, though, how the distribution of such floral traits within plant communities changes along an urbanisation gradient. This study aims to understand to which extent floral traits known to attract pollinators are filtered by urban environments. We used dry grassland, spanning a broad urbanisation gradient in the Berlin metropolitan area, Germany, as a model ecosystem and identified the distribution of plant traits related to bee-perceived flower colours, UV reflection and flower size in 47 grassland patches. We analysed how these traits were related to abiotic and biotic factors at different spatial scales. The most influent predictor was an abiotic factor measured at the landscape scale: the proportion of impervious surface, found to be positively related to UV-reflectance strength and floral UV patterns, but negatively to floral size diversity. At the local scale, abiotic factors showed an intermediary number of relationships. Temperature was negatively associated with the bee-colour 'green + UV-green' and with flower size. The light environment was negatively related to the same bee-colour and to floral size diversity. Biotic factors related to local pollinator communities were less important: species richness was negatively related to flower size, while proportion of bees to floral sizes diversity. This study shows that floral traits known to attract pollinators are mostly filtered by abiotic factors related to urbanisation (share of impervious surface) or the urban heat island (local temperature). Biotic factors related to local pollinator communities were less important. These results increase our functional understanding of plant-animal interactions in cities by illustrating how urban environments modulate the attractiveness of plant communities to pollinators by filtering for floral plant traits.

International audience; This study was designed to test if heart rate variability (HRV) data from preterm and full-term infants could be used to estimate their functional maturational age (FMA), using a machine learning model. We propose that the FMA, and its deviation from the postmenstrual age (PMA) of the infants could inform physicians about the progress of the maturation of the infants. The HRV data was acquired from 50 healthy infants, born between 25 and 41 weeks of gestational age, who did not present any signs of abnormal maturation relative to their age group during the period of observation. The HRV features were used as input for a machine learning model that uses filtering and genetic algorithms for feature selection, and an ensemble machine learning (EML) algorithm, which combines linear and random forest regressions, to produce as output a FMA. Using HRV data, the FMA had a mean absolute error of 0.93 weeks, 95% CI [0.78, 1.08], compared to the PMA. These results demonstrate that HRV features of newborn infants can be used by an EML model to estimate their FMA. This method was also generalized using respiration rate variability (RRV) and bradycardia data, obtaining similar results. The FMA, predicted either by HRV, RRV or bradycardia, and its deviation from the true PMA of the infants, could be used as a surrogate measure of the maturational age of the infants, which could potentially be monitored non-invasively and in real-time in the setting of neonatal intensive care units.

Therapy resistance represents a major clinical challenge in acute myeloid leukemia (AML). Here we define a ‘MitoScore’ signature, which identifies high mitochondrial oxidative phosphorylation in vivo and in patients with AML. Primary AML cells with cytarabine (AraC) resistance and a high MitoScore relied on mitochondrial Bcl2 and were highly sensitive to venetoclax (VEN) + AraC (but not to VEN + azacytidine). Single-cell transcriptomics of VEN + AraC-residual cell populations revealed adaptive resistance associated with changes in oxidative phosphorylation, electron transport chain complex and the TP53 pathway. Accordingly, treatment of VEN + AraC-resistant AML cells with electron transport chain complex inhibitors, pyruvate dehydrogenase inhibitors or mitochondrial ClpP protease agonists substantially delayed relapse following VEN + AraC. These findings highlight the central role of mitochondrial adaptation during AML therapy and provide a scientific rationale for alternating VEN + azacytidine with VEN + AraC in patients with a high MitoScore and to target mitochondrial metabolism to enhance the sensitivity of AML cells to currently approved therapies. Sarry and colleagues demonstrate that adaptive resistance to venetoclax + cytarabine therapy in acute myeloid leukemia relies on mitochondrial respiration and show that combination with electron transport chain complex inhibitors delays relapse in patient-derived xenograft models in vivo.

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International audience; We show that the long-term properties of price and cost in Chamberlin's (1933) monopolistic competition model can be reproduced with a soft-capacity constrained price competition oligopoly model for a homogeneous good with free entry.

International audience; A newborn is preterm if birth occurred before a gestational age of 37 weeks. He has several immature functions, which implies a specific monitoring and, among others, the analysis of its sleep. Here we make a focus on Quiet Sleep (QS), whose increasing is primordial with age, and characterized by an absence of motion and a regular cardiorespiratory rhythm. A method to automatically detect QS is proposed, on the basis of a video analysis (detection of motion), supplemented by the estimation of ECG and respiration 'qualities'. This approach combines feature extraction and machine learning methods. It was validated on a set of 15 newborns and 25 eight-hours recordings manually annotated. Best results were obtained by combining non-motion intervals and ECG quality, but showing also an overestimation of QS (Se=88%, Sp=49%). However, regarding extracted features, we observed similar trends between manual and automated QS, with an increasing of average duration of QS intervals and percentage of time in QS with age, also approaching values of the full-term newborns. Finally, computation of QS on a larger set of 45 recordings confirmed the interest of the approach for maturation evaluation purposes. © 2021 Creative Commons.

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We consider a model of price competition in a homogeneous good, with soft-capacity constraints, in the special case of a Sone-Geary production function that implies a minimum firm size and leads to a U-shaped average cost function. We study free entry and obtain a Chamberlin-like result: zero profit and a positive markup at equilibrium.

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Background Severe asthma (SA) in children is a complex, heterogeneous disease, associated with a considerable burden. However, factors influencing asthma severity are poorly described and may differ according to age. Objective To determine whether factors associated with asthma severity differ between preschoolers with severe recurrent wheeze (SRW) and school-age children with SA. Methods Data from the French multicenter prospective observational cohort of preschool (3-6 years) children with SRW and nonsevere recurrent wheeze (NSRW) and school-age (7-11 years) children with SA and nonsevere asthma (NSA) (Pediatric Cohort of Bronchial Obstruction and Asthma) were analyzed. Results A total of 131 preschool children (92 SRW and 49 NSRW) and 207 school-age children (92 SA and 115 NSA) were included. In both univariable and multivariable analysis, SRW was associated with second-hand smoke exposure (multivariable analysis: odds ratio [95% CI], 29.8 [3.57-3910]) and exposure to mold/dampness at home (multivariable analysis: odds ratio [95% CI], 4.22 [1.25-18.2]) compared with NSRW. At school-age, history of atopic dermatitis and food allergy was more frequent in children with SA than in those with NSA. Multivariable analysis confirmed that SA was associated with a history of food allergy (odds ratio [95% CI], 5.01 [2.23-11.9]). Conclusions Our data suggest that factors influencing asthma severity may differ according to age. In preschool children with SRW, second-hand smoke and exposure to mold are predominant, whereas associated allergic disorders are mainly involved in SA at school-age.

International audience; Video-based motion analysis recently appeared to be a promising approach in neonatal intensive care units for monitoring the state of preterm newborns since it is contact-less and noninvasive. However it is important to remove periods when the newborn is absent or an adult is present from the analysis. In this paper, we propose a method for automatic detection of preterm newborn presence in incubator and open bed. We learn a specific model for each bed type as the camera placement differs a lot and the encountered situations are different between both. We break the problem down into two binary classifications based on deep transfer learning that are fused afterwards: newborn presence detection on the one hand and adult presence detection on the other hand. Moreover, we adopt a strategy of decision intervals fusion in order to take advantage of temporal consistency. We test three deep neural network that were pre-trained on ImageNet: VGG16, MobileNetV2 and InceptionV3. Two classifiers are compared: support vector machine and a small neural network. Our experiments are conducted on a database of 120 newborns. The whole method is evaluated on a subset of 25 newborns including 66 days of video recordings. In incubator, we reach a balanced accuracy of 86%. In open bed, the performance is lower because of a much wider variety of situations whereas less data are available.

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International audience; BACKGROUND: In the European Union, 300,000 newborn babies are born prematurely every year. Their care is ensured in Neonatal Intensive Care Units (NICU) where vital signs are constantly monitored. In addition, other descriptors such as motion, facial and vocal activities have been shown to be essential to assess neurobehavioral development. AIM: In the scope of the European project Digi-NewB, we aimed to develop and evaluate a new audio-video device designed to non-invasively acquire multi-modal data (audio, video and thermal images), while fitting the wide variety of bedding environment in NICU. METHODS: Firstly, a multimodal system and associated software and guidelines to collect data in neonatal intensive care unit were proposed. Secondly, methods for post-evaluation of the acquisition phase were developed, including the study of clinician feedback and a qualitative analysis of the data. RESULTS: The deployment of 19 acquisition devices in six French hospitals allowed to record more than 500 newborns of different gestational and postmenstrual ages. After the acquisition phase, clinical feedback was mostly positive. In addition, quality of more than 300 recordings was inspected and showed that 77% of the data is exploitable. In depth, the percentage of sole presence of the newborn was estimated at 62% within recordings. CONCLUSIONS: This study demonstrates that audio-video acquisitions are feasible on a large scale in real life in NICU. The experience also allowed us to make a clear observation of the requirements and challenges that will have to be overcome in order to set up audio-video monitoring methods.

Infectious hematopoietic necrosis virus (IHNV) is a pathogen of importance for salmonid aquaculture. In this study, we aimed to characterize virus behavior and defense mechanisms developed in rainbow trout (RT, Oncorhynchus mykiss) experimentally infected with isolates belonging to the five described genotypes of IHNV, i.e. L, U, M, E and J. Mortality was monitored for two months, and blood and target organs were sampled at different times post-infection to assess viral load and cellular and humoral immune responses. Profiles of virulence were highly linked to precocious viral replication but also to the innate and specific immunity elicited in the host. Seroneutralization test (SNT) used for specific antibodies detection exhibited reliable results, with efficient cross-neutralization observed in heterologous systems except for the Asian representative. These data bring new insights about IHNV/RT interaction and reinforce the interest of SNT as preventive and epidemiological tool.

Radio-over-fiber (RoF) systems can be incorporated into a wavelength division multiplexing (WDM) and distributed antenna system (DAS) to vastly increase the data throughput. In this paper, a reconfigurable WDM system at millimeter (mm-wave) frequencies is theoretically proposed and experimentally demonstrated based on an optical frequency comb (OFC) and wavelength selective switch (WSS). The photonic carrier generation using OFC spectra is affected by chromatic dispersion which results in power fading and optical noise. Therefore, the tolerance of the mm-wave heterodyne carrier to fiber propagation is discussed and considered in the proposed architecture. Furthermore, this paper examines how the WSS can pre-compensate the fiber dispersion in terms of power fading on the beating carrier. Experimental measurements show that by variable adjustment of the amount of dispersion compensation applied, power fading of 15 dB can be mitigated and error vector magnitude (EVM) is reduced by 10 % . By utilizing the well-known periodic behavior between carrier power penalty and chromatic dispersion, the WSS can also overcome the deep power fading over long fiber lengths ( > 25 km).

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International audience

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International audience; Le vieillissement de la population active et les changements technico-organisationnels fréquents au travail renforcent, pour nombre d’entreprises, les enjeux de prévention des problèmes de santé et de maintien en emploi des personnes rencontrant déjà des difficultés. La recherche-intervention présentée ici a été menée en collaboration avec quatre grandes entreprises. Elle soutient une approche originale de ces questions, basée sur l’analyse des régulations « de et dans le travail », réputées « invisibles », et favorable à la compréhension et la prise en charge des processus de fragilisation au travail. Après avoir exposé les principaux résultats issus d’une analyse démographique et ergonomique croisée dans deux entreprises, le texte détaille la démarche mise en place auprès et avec les acteurs des quatre entreprises pour la construction des voies d’une prévention durable des processus de fragilisation au travail. Celle-ci s’appuie sur la co-construction et l’animation d’« ateliers coopératifs », d’une part, et sur la co-élaboration d’un « outil-repères » pour le diagnostic et la prise en charge de ces processus, d’autre part. Cette démarche propose de saisir en évolution les ingrédients de la fragilisation, en soutenant plusieurs déplacements théoriques et méthodologiques renouvelant les modalités d’analyse et d’action.

We propose a novel procedure for outlier detection in space telemetries, in a semi-supervised framework. As the data is functional, we reduce its dimension by considering the coefficients obtained after projecting the observations onto orthonormal bases. A multiple testing procedure based on the two-sample test is defined in order to highlight the levels of the coefficients on which the outliers appear as significantly different from the nominal data. The Local Outlier Factor is computed on the selected coefficients to highlight the outliers. This procedure for selecting the features is applied on simulated data that mimic the behavior of space telemetries and on a real telemetry and then compared with existing dimension reduction techniques.

International audience; Cry analysis of preterm newborns has proven to be relevant for prediction of pathologies or for comparison with full-term newborns. In this paper we propose a new approach for the automated detection and tracking of the fundamental frequency in cries, based on the processing of the spectrogram. A first step automatically detects the frequency bounds including the fundamental frequency along each cry. Then, the tracking of the fundamental frequency is obtained after a contour detection. Results showed that this new approach allows to process efficiently all types of cries. This whole procedure applied to a database including 1889 cries from 14 babies, at term-equivalent age, highlighted differences between extremely, very and late preterm as well as full-term newborns. In addition, we observed a decrease of the mean fundamental frequency with increasing gestational age, a result in accordance with the literature. © 2021 European Signal Processing Conference, EUSIPCO. All rights reserved.

International audience; Cry analysis has been proven to be an inescapable tool to evaluate the development of preterm infants. However, to date, only a few authors proposed to automatically extract spontaneous cry events in the real context of Neonatal Intensive Care Units. In fact, this is challenging since a wide variety of sounds can also occur (e.g., alarms, adult voice). In this communication, a new method for spontaneous cry extraction from real life recordings of long duration is presented. A strategy based on an initial segmentation between silence and sound events, followed by a classification of the resulting audio segments into two classes (cry and non-cry) is proposed. To build the classification model, 198 cry events coming from 21 newborns and 439 non-cry events, representing the richness of the clinical sound environment were annotated. Then, a set of features, including Mel-Frequency Cepstral Coefficients, was computed in order to describe each audio segment. It was obtained after Harmonic plus Noise analysis which is commonly used for speech synthesis although never applied for newborn cry analysis. Finally, six machine learning approaches have been compared. K-Nearest Neighbours approach showed an accuracy of 94.1%. To experience the precision of the retained classifier, 412 hours of recordings of 23 newborns were also automatically processed. Results show that despite a difficult clinical context an automatic extraction of cry is achievable. This supports the idea that a new generation of non-invasive monitoring of neuro-behavioral development of premature newborns could emerge. © 2021 European Signal Processing Conference, EUSIPCO. All rights reserved.

International audience; In this paper, we compare the distributions of socially optimal public funding between private and public research sectors in cooperative and non-cooperative R&D settings in the presence of externalities. We show that the proportion of public funding allocated to the private sector research always increases with the level of inter-firm spillovers but decreases with the concentration of the industry. This share is smaller (larger) when firms cooperate in R&D than when they do not for high (low) spillovers. Moreover, increases in public knowledge externalities to the private sector due to a closer proximity between the two research sectors increase the share allocated to the public sector regardless of whether firms cooperate or not in R&D.

Objectives Apoptosis-Inducing Factor (AIF) is a protein involved in mitochondrial electron transport chain assembly/stability and programmed cell death. The relevant role of this protein is underlined because mutations altering mitochondrial AIF properties result in acute pediatric mitochondriopathies and tumor metastasis. By generating an original AIF-deficient mouse strain, this study attempted to analyze, in a single paradigm, the cellular and developmental metabolic consequences of AIF loss and the subsequent oxidative phosphorylation (OXPHOS) dysfunction. Methods We developed a novel AIF-deficient mouse strain and assessed, using molecular and cell biology approaches, the cellular, embryonic, and adult mice phenotypic alterations. Additionally, we conducted ex vivo assays with primary and immortalized AIF knockout mouse embryonic fibroblasts (MEFs) to establish the cell death characteristics and the metabolic adaptive responses provoked by the mitochondrial electron transport chain (ETC) breakdown. Results AIF deficiency destabilized mitochondrial ETC and provoked supercomplex disorganization, mitochondrial transmembrane potential loss, and high generation of mitochondrial reactive oxygen species (ROS). AIF-/Y MEFs counterbalanced these OXPHOS alterations by mitochondrial network reorganization and a metabolic reprogramming toward anaerobic glycolysis illustrated by the AMPK phosphorylation at Thr172, the overexpression of the glucose transporter GLUT-4, the subsequent enhancement of glucose uptake, and the anaerobic lactate generation. A late phenotype was characterized by the activation of P53/P21-mediated senescence. Notably, approximately 2% of AIF-/Y MEFs diminished both mitochondrial mass and ROS levels and spontaneously proliferated. These cycling AIF-/Y MEFs were resistant to caspase-independent cell death inducers. The AIF-deficient mouse strain was embryonic lethal between E11.5 and E13.5 with energy loss, proliferation arrest, and increased apoptotic levels. Contrary to AIF-/Y MEFs, the AIF KO embryos were unable to reprogram their metabolism toward anaerobic glycolysis. Heterozygous AIF+/- females displayed progressive bone marrow, thymus, and spleen cellular loss. In addition, approximately 10% of AIF+/- females developed perinatal hydrocephaly characterized by brain development impairment, meningeal fibrosis, and medullar hemorrhages; those mice died 5 weeks after birth. AIF+/- with hydrocephaly exhibited loss of ciliated epithelium in the ependymal layer. This phenotype was triggered by the ROS excess. Accordingly, it was possible to diminish the occurrence of hydrocephalus AIF+/- females by supplying dams and newborns with an antioxidant in drinking water. Conclusions In a single knockout model and at 3 different levels (cell, embryo, and adult mice) we demonstrated that by controlling the mitochondrial OXPHOS/metabolism, AIF is a key factor regulating cell differentiation and fate. Additionally, by providing new insights into the pathological consequences of mitochondrial OXPHOS dysfunction, our new findings pave the way for novel pharmacological strategies., Highlights • Mitochondrial AIF loss triggers OXPHOS/metabolism impairment. • AIF-/Y MEFs reprogram their metabolism by enabling an AMPK/GLUT-4 glycolytic pathway. • OXPHOS dysfunction associated with AIF loss generates a P53/P21 senescent phenotype. • The lack of metabolic plasticity provokes embryonic lethality in the AIF KO animals. • AIF+/- females develop immune cell exhaustion and perinatal hydrocephaly.

Aquatic ecosystems are now chronically polluted by a cocktail of many chemical substances. There is now clear evidence of associations between exposure to pollutants and greater susceptibility to pathogens. The aim of the present study was to characterize the defense capacities of rainbow trout (Oncorhynchus mykiss), chronically exposed to pendimethalin (PD), to subsequent experimental challenge with the infectious hematopoietic necrosis virus (IHNV). Immunological responses were examined at different organizational levels, from individuals to gene expression. No negative effects of PD were noted on the Fulton index nor on the liver or spleen somatic indices (LSI; SSI) before viral infection, but the infectious stress seems to generate a weak but significant decrease in Fulton and LSI values, which could be associated with consumption of energy reserves. During the viral challenges, the distribution of cumulative mortality was slightly different between infected groups. The impact of the virus on fish previously contaminated by PD started earlier and lasted longer than controls. The proportion of seropositive fish was lower in the fish group exposed to PD than in the control group, with similar quantities of anti-IHNV antibodies secreted in positive fish, regardless of the treatment. While no significant differences in C3-1 expression levels were detected throughout the experiment, TNF1&2, TLR3, Il-1β and IFN expression levels were increased in all infected fish, but the difference was more significant in fish groups previously exposed to herbicide. On the other hand, β-def expression was decreased in the pendimethalin-IHNV group compared to that in fish only infected by the virus (control-IHNV group).

Background: Anti-TNF are effective drugs in induction and maintenance treatment of moderate to severe inflammatory bowel diseases (IBD) and are an undeniable progress. The patent for adalimumab fell into the public domain in 2018, leading to the arrival of several biosimilars, representing potential health-cost saving and research reinvestment. While studies of non-inferiority have proven similar efficacy and safety to Humira® in psoriasis notably, real-life data in IBD are expected. Reducing the nocebo effect (NE) of a switch is also a challenge. Objective: One-year observational prospective multicentric real-life study evaluating IBD patients in remission who switch Humira® for one of its biosimilars. Main objective: to assess the magnitude of the NE. Secondary objectives: maintaining efficacy, safety and 1-year adherence factors to switch. Materials and methods : 200 quiescient IBD patients for 3 months under Humira® are proposed to switch to one of its biosimilars after receiving information and signing the consent. They are clinically and biologically monitored every 3 months for one year, and fill-up 3 questionnaires (BMQ, SATMED-Q, IBD Disk) at each appointment. Results: Primary endpoint: percentage of patients who switch back to Humira® without any objective markers of inflammation during 1 year. Secondary endpoints: percentage of clinical remission, biological, clinical response, loss of response and adverse effects at one year. Risk factors for an NE are assess by the questionnaires every 3 months. Conclusion: First real-life French data evaluating the one-year impact of Adalimumab originator switch to one of its biosimilars in IBD patients in remission.; Contexte : Les anti-TNF sont efficaces dans le traitement des MICI et sont un progrès incontestable. Le brevet de l’adalimumab étant tombé dans le domaine public en 2018, ses biosimilaires sont arrivés, représentant une possibilité d’économie et de réinvestissement dans la recherche. Des études de non infériorité ont prouvé leur efficacité et sécurité équivalentes à l’Humira® dans le psoriasis notamment. Des données de vraie vie dans les MICI sont aujourd’hui attendues. Atténuer l’effet nocébo (EN) d’un switch est aussi un challenge. Objectif : Essai multicentrique prospectif observationnel chez des patients MICI en rémission un an après leur switch de l’Humira® vers un de ses biosimilaires. L’objectif Ire est d’évaluer l’amplitude de l’EN. Les objectifs 2daires sont le maintien d’efficacité, la sécurité et les facteurs d’adhésion au switch sur 1 an de suivi. Matériel et méthodes : 200 MICI en rémission depuis ≥ 3 mois sous Humira® switchent vers un biosimilaire après information et avoir signé le consentement. Ils sont suivis tous les 3 mois un an cliniquement et biologiquement et remplissent 3 questionnaires (BMQ, SATMED-Q, IBD Disk) à chaque consultation. Résultats : Critère principal de jugement : pourcentage de patients qui repassent dans l’année à l’Humira® sans marqueurs objectifs d’inflammation. Critères secondaires : pourcentage de rémission clinique, biologique, réponse clinique, perte de réponse et effets indésirables à un an. Les facteurs favorisant un EN sont explorés par les questionnaires tous les 3 mois. Conclusion : Nous apporterons les premières données françaises de vraie vie chez des MICI un an après leur « switch » de l’Humira® vers un biosimilaire.

The airway epithelium represents a fragile environmental interface potentially disturbed by cigarette smoke (CS), the major risk factor for developing chronic obstructive pulmonary disease (COPD). CS leads to bronchial epithelial damage on ciliated, goblet, and club cells, which could involve calcium (Ca

Radio-over-fiber systems can be harnessed to generate millimeter-wave (mm-wave) frequencies, but the optical impairments such as optical noise, chromatic dispersion, and nonlinearity can degrade the quality of the generated heterodyne signals. When optical frequency comb sources are employed, chromatic dispersion has a main importance since it causes a phase shift and phase decorrelation between optical lines. These both effects subsequently induce power fading and also optical noise on the beat note carrier. With utilizing ultrawide optical spectra, higher order dispersion coefficients must be considered during the propagation across optical fiber, which introduces a high level of complexity in the analytic model. In this paper, we present a simple and convenient model to analyze the impact of chromatic dispersion on the power of the mm-wave heterodyne carrier. The proposed model manipulates and integrates the higher order dispersion terms into an equivalent second-order dispersion term. This allows to perform the easiest way to calculate the propagation constant. Simulation and experimental results are conducted for fiber distance up to 30 km in order to validate the suggested model in terms of the carrier power. Through the results obtained, the well-known behavior between the signal power and chromatic dispersion can be modified. Optical phase shift results in a diverse power fading and intensity noise while optical phase de-correlation manifests phase noise. Therefore, data transmission over 25 km fiber is carried out to show the impact of chromatic dispersion on optical noise of the beating carrier. RF power and error vector magnitude reveal that the chromatic dispersion can overcome power fading and increase the tolerance to fiber length with limiting the optical noise in the optical heterodyning system.

The objective of this work, conducted as part of the European project Digi-NewB and a CIFRE thesis, was to propose a new noninvasive approach to monitoring in neonatal intensive care units (NICUs). This new monitoring should make possible a continuous evaluation of the neuro-behavioural evolution of premature newborns using non-invasive modalities such as video and audio. After a bibliographical study of more than 150papers, a first study was carried out on a semiautomatic estimation of sleep stages. The proposed approach combined for the first time video and audio analyses. The limitations identified during this study led to the proposition of a new audio-video system. Its integration into NICU was studied and evaluated. Then, methods, based on video and audio processing techniques and classification (Random Forest, KNN, Multi-layer Perceptron ...), were proposed. They allow a continuous characterization of the newborn behaviour in terms of movement quantification and cry analysis. The difficulties related to the constraints of the real NICU conditions were studied and solutions to avoid irrelevant periods (e.g.,parents or medical staff in the camera field of view, alarms coming from medical devices) were developed. The results are encouraging and show that it is now possible to imagine a new generation of monitoring based on noninvasive analyses to characterize the neurobehavioural development of the newborn., L'objectif de ces travaux, conduits dans le cadre du projet européen Digi-NewB et d'une thèse CIFRE, était de proposer une nouvelle approche non-invasive de monitoring en unités de soins intensifs néonatales (NICU). Ce nouveau monitoring doit permettre d'évaluer de façon continue l'évolution neurocomportementale des nouveau-nés prématurés à partir de modalités non-invasives telles que la vidéo et l'audio. Après une étude bibliographique de plus de 150 documents, une première étude portant sur une estimation semi-automatique des stades de sommeil a été effectuée. L'approche proposée combinait pour la première fois des analyses vidéo et audio. Les limites identifiées lors de cette étude ont permis de proposer un nouveau système audio-vidéo et d'étudier son intégration en NICU. Des méthodes d'analyse vidéo, du son et de classification (Random Forest, KNN, Réseaux de Neurones…) ont été proposées. Elles permettent une caractérisation continue du comportement des nouveau-nés en termes de quantification des mouvements et d'analyse des pleurs. Les difficultés liées aux contraintes des conditions réelles de NICU ont été étudiées et des solutions pour écarter les périodes non analysables (e.g., parents ou personnel médical dans le champ de la caméra, alarmes provenant des appareils médicaux) ont été développées. Les résultats sont encourageants et montrent qu'il est aujourd'hui possible d'imaginer une nouvelle génération de monitoring basée sur des analyses non-invasives pour caractériser le développement neurocomportemental du nouveau-né.

International audience

International audience; Accompagner l’envie d’entreprendre des étudiants ingénieurs dès le début de leur formation par la pratique encadrée de la gestion d’une véritable entreprise est l’objet de la mise en place du projet « Boîte à mouettes ». Petite par la taille, grande par la globalité de ces activités, cette mini-boîte est l’objet d’une expérience concrète d’entrepreneuriat en s’appuyant sur les pratiques du Learning by Doing. Elle met en œuvre les compétences transversales développées au sein des cursus d’écoles d’ingénieurs : créativité, communication, gestion de projet en mouvement et coopération intra et inter-promotion.

International audience; We thank Drs. Poncet and Sénéchal for their interest and critical reading of our paper. We are well aware of their pioneering work on molecular aspects of cypress pollinosis. However, the focus of our paper was rather on epidemiological, clinical and diagnostic features of peach allergy and not towards molecular pollen determinants. We hereby provide answers to direct questions and notions made by Drs. Poncet and Sénéchal. 1. In regard to literature references, we cited those we found relevant for the scope and purpose of the paper and none of the three reviewers suggested citation of additional publications. To our knowledge, the paper by Hugues et al (2006) was indeed the first to report an association between cypress and peach allergy, and it is cited as reference 39 in our paper 1. However, contrary to the assertion by Poncet and Sénéchal, the authors of that paper did not identify a pollen homologue of Pru p 7, which was first reported as an allergen by Tuppo et al in 2013 2 but instead made the notion "Because both allergenic extracts include a 45 kDa-allergen, it should be the shared allergen." Cup a 1, a major allergen in cypress pollen, has a molecular weight of 43 kDa. Experimental data from the Poncet team are currently available for BP14 and snakin-1, neither of which have been officially recognized and named as allergens by the WHO/IUIS Allergen Nomenclature SubCommittee (www.aller gen.org, accessed May 4 2019). Other papers cited by Poncet et al are either replies or reviews. We prefer citation of original, peer-reviewed research. However, the review on cypress pollinosis is also cited in our paper as ref 41. 3 2. This case report of one patient with discordant FABER IgE and BAT results would have brought little if any further information to the reader. In our hands, the FABER test displays highly sensitive detection of IgE to Pru p 7. 3. As noted above, BP14 has not been officially recognized as an allergen. 4. Snakin-1 is out of the scope of our publication. 5. Recombinant Pru p 7 was biochemically and immunologically characterized as described in section 2.6 4 and additionally by circular dichroism spectroscopy, but, given the focus of the paper, we did not consider it relevant to show and elaborate on such data, nor was there space available. It was also not suggested by any of the three reviewers. However, the BAT results shown in Table S3 demonstrate a similar functional potency of natural and recombinant Pru p 7 which suggests an authentic folding of the recombinant protein. o We do not agree that assessment of anti-microbial activity of recombinant Pru p 7 and several of the other specifics mentioned would be necessary to validate the association between cypress pollen allergy and peach allergy as suggested (but not yet done in their publications) by Drs Poncet and Sénéchal. o The cypress species used was Cupressus sempervirens. o The pollen was extracted and clarified by standard methods. We did not consider total protein concentration to be informative in relation to the purpose of the experiment but chose instead to determine the potency of the extract by titrated inhibition of IgE binding to Pru p 7, as described in section 3.5. That potency determination guided the choice of inhibitor concentration in the single-point inhibitions shown in figure 5A. 15% (w/v) means a concentration corresponding to 15 g of pollen (dry weight) per 100 mL of liquid, a manner of expressing concentrations also used by Poncet et al in their papers. o The specificity of inhibition with the pollen extract was ensured by a complete lack of inhibition of binding of dog dander specific IgE to dog dander ImmunoCAP (e5) and is further indicated by the lack of significant inhibition in some samples as shown in figure 5A. Had the inhibitory effect of the cypress pollen extract been due to unspecific blockade of IgE, no such results would have been obtained. We hope that our response will provide sufficient clarity and explanation to the questions raised by Drs. Poncet and Sénéchal.

Background: Lung disease quantification via medical image analysis is classically difficult. We propose a method based on normalized nearest neighborhood distance classifications for comparing individual CT scan air-trapping distributions (representing 3D segmented parenchyma). Previously, between-image comparisons were precluded by the variation inherent to parenchyma segmentations, the dimensions of which are patient- and image-specific by nature.Method: Nearest neighbor distance estimations are normalized by a theoretical distance according to the uniform distribution of air trapping. This normalization renders images (of different sizes, shapes, and/or densities) comparable. The estimated distances for the k-nearest neighbor describe the proximity of point patterns over the image. Our approach assumes and requires a defined homogeneous space; therefore, a completion pretreatment is applied beforehand.Results: Model robustness is characterized via simulation in order to verify that the required initial transformations do not bias uniformly sampled results. Additional simulations were performed to assess the discriminant power of the method for different point pattern profiles. Simulation results demonstrate that the method robustly recognizes pattern dissimilarity. Finally, the model is applied on real data for illustrative purposes.Conclusion: We demonstrate that a parenchyma-cuboid completion method provides the means of characterizing air-trapping patterns in a chosen segmentation and, importantly, comparing such patterns between patients and images.

International audience

International audience

BACKGROUND: Peach is a common elicitor of food allergic reactions. Peach-induced immediate reactions may occur as benign pollen-food syndromes, usually due to birch pollen-related PR-10 cross-reactivity in temperate climates, and as potentially severe primary food allergies, predominantly related to nsLTP Pru p 3 in Mediterranean regions. The newly described peach allergen Pru p 7 has gained recent attention as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure. OBJECTIVE: We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France. METHODS: Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform. RESULTS: Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests. CONCLUSION AND CLINICAL RELEVANCE: A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy.

International audience

International audience

Dans bien des secteurs professionnels, les horaires de travail réguliers et diurnes sont une norme en recul. On estime actuellement qu’environ la moitié des salariés sont concernés par des horaires de travail « atypiques » – tôt le matin ou tard le soir, de nuit, alternants, en poste long, le week-end, à des horaires imprévisibles. La progression de ces différentes formes de travail atypique n’est pas uniforme, elle touche inégalement les diverses catégories de salariés. Cependant elle concerne un nombre régulièrement croissant de personnes de tous âges et secteurs professionnels. L’édition 2017 du séminaire du Creapt (Centre de Recherche sur l’Expérience, l’Age et les Populations au Travail) a été consacrée à cette thématique, en s’efforçant de la relier aux enjeux de santé, d’expérience, de parcours professionnels. Le présent rapport reprend, sous forme à peu près littérale, les exposés et les échanges auxquels ce séminaire a donné lieu.L’expansion des horaires atypiques ne doit pas être systématiquement associée à une dégradation des conditions de vie et de travail, car elle peut être assortie de compensations jugées acceptables par les travailleurs concernés. Dans certaines situations où ils ont le choix, ils peuvent juger ces horaires préférables à ceux dits normaux. Par ailleurs, avec l’expérience, des stratégies de travail spécifiques à ces horaires décalés peuvent se construire. Cependant des recherches, reprises notamment ici dans la conférence introductive, mettent en évidence leurs effets négatifs sur l’organisme humain et sur la vie sociale, avec des conséquences de plus en plus marquées avec les heures et les années accumulées. Revenir à des horaires « normaux » est parfois souhaité à mi-carrière, quand la fatigue ou les troubles de santé s’amplifient, ou que se déploie une aspiration à une vie familiale et sociale moins perturbée. Mais les réaffectations ne sont pas toujours possibles, ou comportent des contreparties négatives.Les organisations temporelles du travail peuvent ainsi placer les individus dans des situations de conflits de temporalités dont il faut comprendre les enjeux et les effets, à la fois pour la production ou le service et pour la santé et la vie sociale au fil des parcours professionnels. C’est pourquoi les participants à ce séminaire se sont interrogés sur ces cadres temporels du travail, leurs évolutions actuelles dans des secteurs professionnels très variés, leurs enjeux au regard du contenu du travail et de l’activité collective. Les présentations de chercheurs de différentes disciplines et les échanges avec les participants permettent de mieux comprendre leurs effets dans des dimensions individuelles et collectives ainsi que techniques et sociales, à des échelles de court et de long termes.

International audience; Objective - Video and sound acquisition and processing technologies have seen great improvements in recent decades, with many applications in the biomedical area. The aim of this paper is to review the overall state of the art of advances within these topics in paediatrics and to evaluate their potential application for monitoring in the neonatal intensive care unit (NICU). Approach - For this purpose, more than 150 papers dealing with video and audio processing were reviewed. For both topics, clinical applications are described according to the considered cohorts-full-term newborns, infants and toddlers or preterm newborns. Then, processing methods are presented, in terms of data acquisition, feature extraction and characterization. Main results - The paper first focuses on the exploitation of video recordings; these began to be automatically processed in the 2000s and we show that they have mainly been used to characterize infant motion. Other applications, including respiration and heart rate estimation and facial analysis, are also presented. Audio processing is then reviewed, with a focus on the analysis of crying. The first studies in this field focused on induced-pain cries and the newest ones deal with spontaneous cries; the analyses are mainly based on frequency features. Then, some papers dealing with non-cry signals are also discussed. Significance - Finally, we show that even if recent improvements in digital video and signal processing allow for increased automation of processing, the context of the NICU makes a fully automated analysis of long recordings problematic. A few proposals for overcoming some of the limitations are given.