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International audience; Sonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round window membrane could improve the delivery of therapeutics to the inner ear. The aim of this study was to assess the safety of sonoporation of the round window membrane in a sheep model. To achieve this objective, we assessed auditory function and cochlear heating, and analysed the metabolomics profiles of perilymph collected after sonoporation, comparing them with those of the control ear in the same animal. Six normal-hearing ewes were studied, with one sonoporation ear and one control ear for each. A mastoidectomy was performed on both ears. On the sonoporation side, Vevo MicroMarker® microbubbles (MBs; VisualSonics—Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 × 108 MB/mL were locally injected into the middle ear and exposed to 1.1 MHz sinusoidal ultrasonic waves at 0.3 MPa negative peak pressure with 40% duty cycle and 100 μs interpulse period for 1 min; this was repeated three times with 1 min between applications. The sonoporation protocol did not induce any hearing impairment or toxic overheating compared with the control condition. The metabolomic analysis did not reveal any significant metabolic difference between perilymph samples from the sonoporation and control ears. The results suggest that sonoporation of the round window membrane does not cause damage to the inner ear in a sheep model.

International audience; Objective: Previous studies showed that patients with Psychogenic Non-Epileptic Seizures (PNES) have poor quality of life (QoL). This study explored the explicative factors of the QoL at the time of diagnosis and monitored changes over the two years of follow-up.Methods: We evaluated 107 participants with a diagnosis of Psychogenic Non-Epileptic Seizure (PNES), every 6 months for 24 months. Quality of life (QoL) was evaluated using the QOLIE-31 and SF-36 scales (respectively specific and generic scales of QoL). Positive evolution of QoL was defined by the increase in the score of overall QoL using QOLIE-31 sub-scale from baseline to the last interview of the patient. We also collected for each patient data on psychiatric dimensions (childhood abuse, history of traumatic events, post-traumatic stress disorder (PTSD), depression, anxiety, alexithymia, and dissociation), clinical evolution of seizures and the number of mental health consultations.Results: According to the QOLIE-31 and the SF-36, depression (p ≤ 0.001), anxiety (p < 0.001), alexithymia (p ≤ 0.001), and dissociation (p ≤ 0.004) were related to QoL at the time of the diagnosis. According to SF-36 (mental and physical), PTSD was also significantly associated with QoL (p < 0.05). The number of seizures or the co-occurrence of epilepsy did not influence QoL. Positive evolution of QoL was linked to the number of consultations for mental health issues (p = 0.02).Significance: Post-traumatic dimensions (PTSD, dissociation), alexithymia and psychiatric comorbidities (depression and anxiety disorders) seem to alter QoL in people with PNES. The current study suggests that mental health care improves QoL of patients with PNES.

Highlights • We used an oddball paradigm with vocal stimuli to record hemodynamic responses. • Brain processing of vocal change relies on STG, insula and lingual area. • Activity of the change processing network can be modulated by saliency and emotion. • Brain processing of vocal deviancy/novelty appears typical in adults with autism., Autism Spectrum Disorder (ASD) is currently diagnosed by the joint presence of social impairments and restrictive, repetitive patterns of behaviors. While the co-occurrence of these two categories of symptoms is at the core of the pathology, most studies investigated only one dimension to understand underlying physiopathology. In this study, we analyzed brain hemodynamic responses in neurotypical adults (CTRL) and adults with autism spectrum disorder during an oddball paradigm allowing to explore brain responses to vocal changes with different levels of saliency (deviancy or novelty) and different emotional content (neutral, angry). Change detection relies on activation of the supratemporal gyrus and insula and on deactivation of the lingual area. The activity of these brain areas involved in the processing of deviancy with vocal stimuli was modulated by saliency and emotion. No group difference between CTRL and ASD was reported for vocal stimuli processing or for deviancy/novelty processing, regardless of emotional content. Findings highlight that brain processing of voices and of neutral/ emotional vocal changes is typical in adults with ASD. Yet, at the behavioral level, persons with ASD still experience difficulties with those cues. This might indicate impairments at latter processing stages or simply show that alterations present in childhood might have repercussions at adult age.

International audience; Although there is some data from animal studies, the metabolome of inner ear fluid in humans remains unknown. Characterization of the metabolome of the perilymph would allow for better understanding of its role in auditory function and for identification of biomarkers that might allow prediction of response to therapeutics. There is a major technical challenge due to the small sample of perilymph fluid available for analysis (sub-microliter). The objectives of this study were to develop and validate a methodology for analysis of perilymph metabolome using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Due to the low availability of perilymph fluid; a methodological study was first performed using low volumes (0.8 μL) of cerebrospinal fluid (CSF) and optimized the LC-HRMS parameters using targeted and non-targeted metabolomics approaches. We obtained excellent parameters of reproducibility for about 100 metabolites. This methodology was then used to analyze perilymph fluid using two complementary chromatographic supports: reverse phase (RP-C18) and hydrophilic interaction liquid chromatography (HILIC). Both methods were highly robust and showed their complementarity, thus reinforcing the interest to combine these chromatographic supports. A fingerprinting was obtained from 98 robust metabolites (analytical variability

International audience; Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown etiology. Mobile communication antennas have increased over the last few decades. Consequently, there has been a steady increase in environmental exposure to ultra high frequency electromagnetic fields (UHF-EMFs) emitted by Global System for Mobile (GSM) communication antennas, which raises concerns about possible health risks in the general population. We aimed to evaluate the relationship between residential exposure to UHF-EMFs generated by GSM antennas and the risk of ALS in general population. A geo-epidemiological population-based study was performed in Limousin (France). ALS incident cases were identified through a register (FRALim, 2000-2012 period). A model to estimate UHF-EMF exposure was developed based on the distance and the power of GSM antennas. Exposure to multiple emissions from multiple directions was considered. A non-cumulative and a cumulative model were established. A geographic information system integrated the raster model of exposure, and the residential distribution of observed and expected cases. A generalized linear model was performed to test the association. Overall, 312 ALS cases were included. We estimated exposures below 1.72 V/m in urban areas and below 1.23 V/m in rural areas for 90% of the population. A gradient effect between UHF-EMF exposure and ALS incidence was apparent with a statistically significant trend. A significant increased risk of ALS was observed between the non-exposure category and the highest exposure category, with a relative risk of 1.78 (95% CI: 1.28-2.48) in the non-cumulative model and 1.83 (95% CI: 1.32-2.54) in the cumulative model. Our results suggest a possible association between residential UHF-EMF exposure and ALS. Ecological studies are a means of generating hypotheses. Further studies are needed to clarify the potential role of EMFs on neurodegeneration.

Thrombosis is a major cause of several diseases, i.e. myocardial infarction, cerebral stroke and pulmonary embolism. Thrombolytic therapies are required to induce fast and efficient recanalization of occluded vessels. To evaluate the in vitro efficacy of these thrombolytic strategies, measuring clot dissolution is essential. This study aimed to evaluate and validate high resolution ultrasound as a tool to assess the exact volume of clots in 3D and in real time during in vitro thrombolytic drug testing. This new method was validated by measuring the effects of concentration range of recombinant tissue type plasminogen activator on a blood clot during complete occlusion or 70% stenosis of a vessel. This study shows that high resolution ultrasound imaging allows for a real-time assessment of the 3D volume of a blood clot with negligible inter- and intra-operator variabilities. The conclusions drawn from this study demonstrate the promising potential of high resolution ultrasound imaging for the in vitro assessment of new thrombolytic drugs.

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Introduction: Prenatal ultrasound (US) anomalies are detected in around 5%–10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on the inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following the detection of anomalies on US.Patients and methods: We prospectively performed prenatal trio-ES in 150 fetuses with at least two US anomalies or one US anomaly known to be frequently linked to a genetic disorder. Trio-ES was only performed if the results could influence pregnancy management. Chromosomal microarray (CMA) was performed before or in parallel.Results: A causal diagnosis was identified in 52/150 fetuses (34%) with a median time to diagnosis of 28 days, which rose to 56/150 fetuses (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) fetuses and unfavorable vital and/or neurodevelopmental prognosis was made in 13/56 (24%) fetuses. The overall diagnostic yield was 41% (37/89) with first-line trio-ES versus 31% (19/61) after normal CMA. Trio-ES and CMA were systematically concordant for identification of pathogenic CNV.Conclusion: Trio-ES provided a substantial prenatal diagnostic yield, similar to postnatal diagnosis with a median turnaround of approximately 1 month, supporting its routine implementation during the detection of prenatal US anomalies.

The analysis of biomedical time series derived from nonlinear dynamic systems is challenging due to the chaotic nature of these time series. Only few classical parameters can be detected by clinicians to opt the state of patients and fetuses. Though there exist valuable complexity invariants such as multi-fractal parameters, entropies and recurrence plots, they were unsatisfactory in certain cases. To overcome this limitation, we propose in this dissertation new entropy invariants, we contributed to multi-fractal analysis and we developed signal-based (unbiased) recurrence plots and unbiased recurrence descriptors based on the dynamic transitions of time series.Principally, we aim to improve the discrimination between healthy and distressed biomedical systems, particularly fetuses by processing the time series using our techniques. These techniques were either validated on Lorenz systems, logistic maps or fractional Brownian motions which model chaotic and random time series. Then the techniques were applied to real fetus heart rate signals recorded from patients in the third trimester of pregnancy. Statistical measures comprising the relative error, standard deviation, sensitivity, specificity, precision and accuracy were employed to evaluate the performance of detection.Elevated discernment outcomes were realized by the high-order entropy invariants developed. Multi-fractal analysis using a structure function and coarse-graining enhanced the detection of the medical states of the fetuses. Unbiased cross-determinism invariant developed amended the discrimination process. The significance of our techniques lies behind their post-processing codes which could build up cutting-edge portable machines offering advanced discrimination and detection of Intrauterine Growth Restriction prior to fetal death. This work was devoted to Fetal Heart Rates but time series generated by alternative nonlinear dynamic systems should be further considered., L′analyse de séries temporelles biomédicales chaotiques tirées de systèmes dynamiques non-linéaires est toujours un challenge difficile à reveler puisque dans certains cas bien spécifiques les techniques existantes basées sur les multi-fractales, les entropies et les graphes de récurrence échouent. Pour contourner les limitations des invariants précé- dents, de nouveaux descripteurs peuvent être proposés. Dans ce travail de recherche nos contributions ont porté à la fois sur l’amélioration d’indicateurs multi-fractals (basés sur une fonction de structure) et entropiques (approchées) mais aussi sur des indicateurs de récurrences (non biaisés).Ces différents indicateurs ont été développés avec pour objectif majeur d’améliorer la discrimination entre des signaux de complexité différente ou d’améliorer la détection de transitions ou de changements de régime du système étudié. Ces changements agissant directement sur l’irrégularité du signal, des mouvements browniens fractionnaires et des signaux tirés du système du Lorenz ont été testés. Ces nouveaux descripteurs ont aussi été validés pour discriminer des fœtus en souffrance de fœtus sains durant le troisième trimestre de grossesse. Des mesures statistiques telles que l’erreur relative, l’écart type, la spécificté, la sensibilité ou la précision on été utilisées pour évaluer les performances de la détection ou de la classification.Le fort potentiel de ces nouveaux invariants nous laisse penser qu’ils pourraient constituer une forte valeur ajoutée dans l’aide au diagnostic s’ils étaient implémentés dans des logiciels de post-traitement ou dans des dispositifs biomédicaux. Enfin, bien que ces différentes méthodes aient été validées exclusivement sur des signaux fœtaux, une future étude incluant des signaux tirés d’autres systèmes dynamiques non-linéaires sera réalisée pour confirmer leurs bonnes performances.

International audience; Pharmacotherapies for the treatment of major depressive disorder were serendipitously discovered almost seven decades ago. From this discovery, scientists pinpointed the monoaminergic system as the primary target associated with symptom alleviation. As a result, most antidepressants have been engineered to act on the monoaminergic system more selectively, primarily on serotonin, in an effort to increase treatment response and reduce unfavorable side effects. However, slow and inconsistent clinical responses continue to be observed with these available treatments. Recent findings point to the glutamatergic system as a target for rapid acting antidepressants. Investigating different cohorts of depressed individuals treated with serotonergic and other monoaminergic antidepressants, we found that the expression of a small nucleolar RNA, SNORD90 , was elevated following treatment response. When we increased Snord90 levels in the mouse anterior cingulate cortex (ACC), a brain region regulating mood responses, we observed antidepressive-like behaviors. We identified neuregulin 3 ( NRG3 ) as one of the targets of SNORD90 , which we show is regulated through the accumulation of N 6 -methyladenosine modifications leading to YTHDF2-mediated RNA decay. We further demonstrate that a decrease in NRG3 expression resulted in increased glutamatergic release in the mouse ACC. These findings support a molecular link between monoaminergic antidepressant treatment and glutamatergic neurotransmission.

International audience; This paper proposes a combined coarse-grained multifractal method to discriminate between dis-tressed and normal foetuses. The coarse-graining operation was performed by means of a coarse-grained procedure and the multifractal operation was based on a structure function. The proposed method was evaluated by one hundred recordings including eighty normal foetuses and twenty dis-tressed foetuses. We found that it was possible to discriminate between distressed and normal foetuses using the Hurst exponent, singularity and Holder spectra.

International audience; Segmentation of brain tumor images, to refine the detection and understanding of abnormal masses in the brain, is an important research topic in medical imaging. This paper proposes a new segmentation method, consisting of three main steps, to detect brain lesions using magnetic resonance imaging (MRI). In the first step, the parts of the image delineating the skull bone are removed, to exclude insignificant data. In the second step, which is the main contribution of this study, the particle swarm optimization (PSO) technique is applied, to detect the block that contains the brain lesions. The fitness function, used to determine the best block among all candidate blocks, is based on a two-way fixed-effects analysis of variance (ANOVA). In the last step of the algorithm, the K-means segmentation method is used in the lesion block, to classify it as a tumor or not. A thorough evaluation of the proposed algorithm was performed, using: (1) a private MRI database provided by the Kouba imaging center—Algiers (KICA); (2) the multimodal brain tumor segmentation challenge (BraTS) 2015 database. Estimates of the selected fitness function were first compared to those based on the sum-of-absolute-differences (SAD) dissimilarity criterion, to demonstrate the efficiency and robustness of the ANOVA. The performance of the optimized brain tumor segmentation algorithm was then compared to the results of several state-of-the-art techniques. The results obtained, by using the Dice coefficient, Jaccard distance, correlation coefficient, and root mean square error (RMSE) measurements, demonstrated the superiority of the proposed optimized segmentation algorithm over equivalent techniques

International audience; Autism Spectrum Disorders (ASD) are a group of developmental disorders caused by environmental and genetic factors. Diagnosis is based on behavioral and developmental signs detected before 3 years of age with no reliable biological marker. The purpose of this study was to evaluate the potential use of a 2D NMR-based approach to express the global biochemical signature of autistic individuals compared to normal controls. This technique has greater spectral resolution than to 1D (1)H NMR spectroscopy, which is limited by overlapping signals. The urinary metabolic profiles of 30 autistic and 28 matched healthy children were obtained using a (1)H-(13)C NMR-based approach. The data acquired were processed by multivariate orthogonal partial least-squares discriminant analysis (OPLS-DA). Some discriminating metabolites were identified: β-alanine, glycine, taurine and succinate concentrations were significatively higher, and creatine and 3-methylhistidine concentrations were lower in autistic children than in controls. We also noted differences in several other metabolites that were unidentified but characterized by a cross peak correlation in (1)H-(13)C HSQC. Statistical models of (1)H and (1)H-(13)C analyses were compared and only 2D spectra allowed the characterization of statistically relevant changes [R(2)Y(cum)=0.78 and Q(2)(cum)=0.60] in the low abundance metabolites. This method has the potential to contribute to the diagnosis of neurodevelopment disorders but needs to be validated on larger cohorts and on other developmental disorders to define its specificity.

International audience; Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders resulting from multiple factors. Diagnosis is based on behavioural and developmental signs detected before 3 years of age, and there is no reliable biological marker. The purpose of this study was to evaluate the value of gas chromatography combined with mass spectroscopy (GC-MS) associated with multivariate statistical modeling to capture the global biochemical signature of autistic individuals. GC-MS urinary metabolic profiles of 26 autistic and 24 healthy children were obtained by liq/liq extraction, and were or were not subjected to an oximation step, and then were subjected to a persilylation step. These metabolic profiles were then processed by multivariate analysis, in particular orthogonal partial least-squares discriminant analysis (OPLS-DA, R(2)Y(cum) = 0.97, Q(2)(cum) = 0.88). Discriminating metabolites were identified. The relative concentrations of the succinate and glycolate were higher for autistic than healthy children, whereas those of hippurate, 3-hydroxyphenylacetate, vanillylhydracrylate, 3-hydroxyhippurate, 4-hydroxyphenyl-2-hydroxyacetate, 1H-indole-3-acetate, phosphate, palmitate, stearate, and 3-methyladipate were lower. Eight other metabolites, which were not identified but characterized by a retention time plus a quantifier and its qualifier ion masses, were found to differ between the two groups. Comparison of statistical models leads to the conclusion that the combination of data obtained from both derivatization techniques leads to the model best discriminating between autistic and healthy groups of children.

International audience; Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders resulting from multiple factors. Diagnosis is based on behavioural and developmental signs detected before 3 years of age, and there is no reliable biological marker. The purpose of this study was to evaluate the value of gas chromatography combined with mass spectroscopy (GC-MS) associated with multivariate statistical modeling to capture the global biochemical signature of autistic individuals. GC-MS urinary metabolic profiles of 26 autistic and 24 healthy children were obtained by liq/liq extraction, and were or were not subjected to an oximation step, and then were subjected to a persilylation step. These metabolic profiles were then processed by multivariate analysis, in particular orthogonal partial least-squares discriminant analysis (OPLS-DA, R(2)Y(cum) = 0.97, Q(2)(cum) = 0.88). Discriminating metabolites were identified. The relative concentrations of the succinate and glycolate were higher for autistic than healthy children, whereas those of hippurate, 3-hydroxyphenylacetate, vanillylhydracrylate, 3-hydroxyhippurate, 4-hydroxyphenyl-2-hydroxyacetate, 1H-indole-3-acetate, phosphate, palmitate, stearate, and 3-methyladipate were lower. Eight other metabolites, which were not identified but characterized by a retention time plus a quantifier and its qualifier ion masses, were found to differ between the two groups. Comparison of statistical models leads to the conclusion that the combination of data obtained from both derivatization techniques leads to the model best discriminating between autistic and healthy groups of children.

International audience; Ultrasound contrast imaging has provided more accurate medical diagnoses. One of the most used techniques is the pulse inversion imaging improving the contrast-to-tissue ratio (CTR) by extracting nonlinearities of contrast agents. The usual transmitted signal is at a fixed frequency. However, an optimal choice requires information about the transducer and the medium. This information is experimentally inaccessible. Moreover, the digital electronic setup can limit the solution. Our goal was to seek the binary command which maximized the CTR. A genetic algorithm sought the vector of input binary samples. By adding a closed loop, the system automatically proposed the optimal binary command without any a priori information about the system or the medium explored and without hypothesis on binary samples. In simulation, the gain compared with a transmitted signal at the optimal frequency can reach about 3 dB and 0.5 dB in comparison with a transmitted signal at the two-thirds of the central frequency of the transducer.

Simulation program available : http://www.runmycode.org/companion/view/1956; International audience; Contrast imaging has significantly improved clinical diagnosis by increasing the contrast-to-tissue ratio after microbubble injection. Pulse inversion imaging is the most commonly used contrast imaging technique, as it greatly increases the contrast-to-tissue ratio by extracting microbubble nonlinearities. The main purpose of our study was to propose an automatic technique providing the best contrast-to-tissue ratio throughout the experiment. For reasons of simplicity, we proposed to maximize the contrast-to-tissue ratio with an appropriate choice of the transmit frequency. The contrast-to-tissue ratio was maximized by a closed loop system including the pulse inversion technique. An algorithm based on the gradient provided iterative determination of the optimal transmit frequency. The optimization method converged quickly after six iterations. This optimal control method is easy to implement and it optimizes the contrast-to-tissue ratio by selecting the transmit frequency adaptively.

International audience; Ultrasound contrast imaging has been introduced in order to increase the contrast of echographic images by injecting micro-bubbles in the vascular system. They are gaz filled microbubbles with nonlinear behavior. One of the most used modality of ultrasound contrast imaging is the second harmonic imaging. This imaging technique, based on the reception of the second harmonic, is devoted to image only the nonlinearity of the microbubble. However, in such ultrasound images the contrast is limited by the nonlinear components of non-perfused tissue. Sub and ultra harmonic imaging appeared to be an interesting alternative to overcome this limitation since, unlike tissue, microbubbles generate sub and ultra harmonics. In order to extract optimally these sub and ultra harmonic components, we proposed a modified Hammerstein model able to model and extract sub and ultra harmonics. Results showed i) that microbubble signal is accurately represented both in time and frequency domains and ii) that sub- and ultra-harmonics were well extracted and separated from harmonic component. Note that the gain achieved by comparing the filtering signals by the modified Hammerstein and the standard Hammerstein was dB.

International audience; Conventional ultrasound contrast imaging systems use sequences of sine waves at a fixed transmit frequency. The excitation of the system is thus a sine wave whose frequency is often fixed around two-thirds of the center frequency of the transducer in the second harmonic imaging. However, this choice requires a knowledge of the transducer and does not take into account the specificities of microbubbles and medium. The main purpose of our study was to propose an automatic technique providing the best contrast-to-tissue ratio by selecting the optimal transmit frequency. The simulations and the experiment showed that the optimal transmit frequency value did not correspond to the usual value. By using the optimized value, the contrast was improved by around 6 dB. Finally, by providing a closed loop system, the system automatically proposed the optimal control without any a priori knowledge of the system or the medium explored.

International audience; Over the past twenty years, in ultrasound imaging, contrast and resolution were improved by using the nonlinearties of the medium. One of the most common techniques which used this properties is the pulse inversion imaging. The optimization of this imaging system that we proposed has consisted in finding the optimal command. However, the properties which enable to make an optimal command was not known and that is why we seek the best optimal command by exciting the system by random sequences. In this study, we proposed two steps in our analysis: an analysis and a modelling stage. The proposed model took into account the nonlinearity of the optimal command and enabled to describe the optimal command by using some parameters. If the synthetic model was used in the pulse inversion imaging system, the contrast can reach the same performances.

The detection of precursor signs of cerebrovascular accidents is a problem of public health since cerebrovascular accidents correspond to the second leading cause of death worldwide. The transcranial Doppler system is used to detect micro-emboli signals. To date, the commercial devices used by clinician did not permit to detect all micro-emboli. New detectors are expected to reduce the false negative rate. We propose a novel detector based on the conditional variance. This detector outperforms the conventionnal detector by a factor 10. Consequently, it will allow a more efficient detection of precursor signs of cerebrovascular accidents and a reducing of the risk for patients., La détection des signes précurseurs d'un accident vasculaire cérébral est un problème de santé publique puisque les accidents vasculaires cérébraux correspondent à la deuxième cause de mortalité dans le monde. Le système Doppler transcrânien est le seul dispositif permettant de détecter les micro-emboles cérébraux. Toutefois, les appareils du commerce existants ne permettent pas encore de détecter automatiquement tous les micro-emboles. Nous proposons alors un nouveau détecteur basé sur un modèle à variance conditionnelle. À partir d'enregistrements obtenus grâce à un système Doppler transcrânien, le nouveau détecteur permet de réduire, d'un facteur 10, le taux de faux négatif affiché par le détecteur d'énergie conventionnel. Ces très bons résultats sont de bonnes augures et ils permettront sans aucun doute une détection plus efficace des signes précurseurs d'un accident vasculaire cérébral et une réduction du risque pour les patients.

ISBN: 978-2-919340-01-9 EAN: 9782919340019; International audience; Over the past twenty years, in ultrasound contrast imaging, new physiological information are obtained by the detection of non-linearities generated by the microbubbles. One of the most used techniques is the pulse inversion imaging. The usual command of this system is a fixed-frequency sinus wave. An optimal choice of this command requires the knowledge of the transducer and of the medium to obtain the best contrast-to-tissue ratio. However, these information are experimentally inaccessible. Our goal is to seek the command which maximizes the contrast-to-tissue ratio. Among several noises, we identified the one which maximized the contrast-to-tissue ratio. A new suboptimal control was made from the parameters of a nonlinear autoregressive filter and from suboptimal noise. The contrast-to-tissue ratio was then iteratively optimized by the method of Nelder-Mead which adjusted the filter parameters. The gain compared to the case in which we used at the optimal frequency can reach about 1 dB and 5 dB in comparison to the center frequency of the transducer. By adding a closed loop, the system automatically proposes the optimal command without any a priori knowledge of the system or of the medium explored and without any hypothesis about the shape of the command.

ISBN: 978-2-919340-01-9; EAN: 9782919340019; International audience; Ultrasound imaging systems usually work in open loop. The system control is thus a sine wave whose frequency is often fixed around two-thirds of the center frequency of the transducer in tissue harmonic imaging. However, this choice requires a knowledge of the transducer and does not take into account the medium properties. Our aim is to seek the command which maximizes the tissue harmonic contrast. We proposed an iterative optimization algorithm that automatically saught for the optimal frequency of the command. Both experimentally and in simulation, its value did not correspond to the usual value. The contrast can be improved by 5 dB. By providing a closed loop system, the system automatically proposes the optimal control without any a priori knowledge of the system or of the medium explored.

Medical ultrasound imaging systems have greatly improved the clinical diagnosis by improving the image quality thanks to more sensitive systems and post-processings. The scientific community has made a great effort of research on post-processing and on encoding the excitation. The methods of the optimal control have been neglected. Our work has focused on the optimal methods based on the feedback from output to input. We have transformed the complex problem of optimal control into an easier suboptimal parametric problem. We apply the principle of optimal control to the ultrasound imaging, the ultrasound harmonic imaging and to the constrast harmonic imaging with or without encoding. The simplicity of the method has allowed us to adapt it to harmonic imaging by a change in the cost function. This adaptation shows that our method can usually be applied to the ultrasound imaging. Nowadays, the stakes of the ultrasound imaging focus not only on the excitation processings or image processings but also on the sensors. This point naturally leads us to seek the optimal control of the capacitive transducers (cMUT) in order to adapt them to the encoded ultrasound imaging. Our compensation and encoding methods by optimal control provide very promising results that go beyond our expectations. The application scope of our methods of optimal control is large and we do not see all the limits yet. The main advantage of our approaches is the easiness of their use and of their implementation. Indeed, our approaches do not require any a priori knowledge on system and medium explored. Our system automatically adapts itself to the changes which may be related to sensor ageing or to the medium change., Les systèmes d'imagerie médicale ultrasonore ont considérablement amélioré le diagnostic clinique par une meilleure qualité des images grâce à des systèmes plus sensibles et des post-traitements. La communauté scientifique de l'imagerie ultrasonore a consenti à un très grand effort de recherche sur les post-traitements et sur le codage de l'excitation sans s'intéresser, outre mesure, aux méthodes de commande optimale. Ce travail s'est donc légitimement tourné vers les méthodes optimales basées sur l'utilisation d'une rétroaction de la sortie sur l'entrée. Pour rendre applicable ces méthodes, ce problème complexe de commande optimale a été transformé en un problème d'optimisation paramétrique sous-optimal et plus simple. Nous avons appliqué ce principe au domaine de l'imagerie ultrasonore : l'échographie, l'imagerie harmonique native et l'imagerie harmonique de contraste avec ou sans codage de la commande. La simplicité de l'approche nous a permis, par une modification de la fonction de coût, de l'adapter à l'imagerie harmonique. Cette adaptation montre que la méthode peut être appliquée à l'imagerie ultrasonore en générale. Aujourd'hui, les enjeux de l'imagerie ultrasonore portent non seulement sur les traitements des excitations ou des images mais aussi sur les capteurs. Ce point nous a conduit naturellement à rechercher la commande optimale des transducteurs capacitifs (cMUT) afin de les adapter à une utilisation plus large en imagerie ultrasonore codée. Nos méthodes de compensation et de codage par commande optimale procurent des résultats très prometteurs qui vont au delà de nos espérances. Le champ d'applications de nos méthodes de codage optimal est large et nous n'en voyons pas forcément encore toutes les limites. L'atout majeur de nos approches est leur simplicité d'utilisation et d'implémentation. En effet, elles ne nécessitent pas d'informations a priori difficilement accessibles sur les outils utilisés ou milieux explorés. Notre système s'adapte automatiquement aux variations qui peuvent être liées au vieillissement du capteur ou à la modification du milieu exploré.

International audience; One aim of comparative neuroanatomy is to better understand brain function among species. It is tempting to try and explain brain differences throughout the animal kingdom by differences in adaptive behaviors as well as ecological factors. Based on this idea, we explored, with MRI, the brain morphology of three species with different sociality and predator avoidance (Bongo, Java deer mouse and Maki Catta). Brains were collected after death of natural causes and MR-imaged. Brain and body weights were collected, and volumes of brain were estimated after MRI segmentation. The brain-to-body weight ratio was close to 1 for the Java deer mouse (1.04%) and the maki catta (1.05%) but only 0.26% for the bongo. Encephalization quotients (EQ) were calculated using formulas defined for human (hEQ, constants 0.12 and 2/3; Cairó 2011, doi:10.3389/fnhum.2011.00108) and for dog (dEQ, constants 0.14 and 0.528; Saganuwan 2021, doi:10.1186/s13104-021-05638-0). Whatever the method, the Java deer mouse EQs were the smallest (hEQ=0.98; dEQ=0.88). The maki catta had a higher hEQ (1.23) than the bongo (1.14) whereas the order was reversed for the dEQ (maki catta dEQ=1.21; bongodEQ=1.96). These values are coherent with the idea that EQ is higher in prey species using active predator avoidance (bongo) and in social species (bongo and maki catta)

Background: Chicken meat has become a major source of protein for human consumption. However, the quality of the meat is not yet under control, especially since pH values that are too low or too high are often observed. In an attempt to get a better understanding of the genetic and biochemical determinants of the ultimate pH, two genetic lines of broilers were divergently selected for low (pHu−) or high (pHu+) breast meat pHu. In this study, the serum lipidome of 17-day-old broilers from both lines was screened for pHu markers using liquid-chromatography coupled with mass spectrometry (LC-HRMS).Results: A total of 185 lipids belonging to 4 groups (glycerolipids, glycerophospholipids, sterols, sphingolipids) were identified in the sera of 268 broilers from the pHu lines by targeted lipidomics. The glycerolipids, which are involved in energy storage, were in higher concentration in the blood of pHu− birds. The glycerophospholipids (phosphatidylcholines, phosphatidylethanolamines) with long and polyunsaturated acyl chains were more abundant in pHu+ than in pHu− while the lysophosphatidylcholines and lysophosphatidylethanolamines, known to be associated with starch, were observed in higher quantity in the serum of the pHu− line. Finally, the concentration of the sterols and the ceramides, belonging to the sphingolipids class, were higher in the pHu+ and pHu−, respectively. Furthermore, orthogonal partial least-squares analyses highlighted a set of 68 lipids explaining 77% of the differences between the two broilers lines (R2Y = 0.77, Q2 = 0.67). Among these lipids, a subset of 40 predictors of the pHu value was identified with a Root Mean Squared Error of Estimation of 0.18 pH unit (R2Y = 0.69 and Q2 = 0.62). The predictive model of the pHu value was externally validated on 68 birds with a Root Mean Squared Error of Prediction of 0.25 pH unit.Conclusion: The sets of molecules identified will be useful for a better understanding of relationship between serum lipid profile and meat quality, and will contribute to define easily accessible pHu biomarkers on live birds that could be useful in genetic selection.

International audience; The transcription factor Krüppel-like factor 10 (Klf10), also known as Tieg1 for TGFβ (Inducible Early Gene-1) is known to control numerous genes in many cell types that are involved in various key biological processes (differentiation, proliferation, apoptosis, inflammation), including cell metabolism and human disease. In skeletal muscle, particularly in the soleus, deletion of the Klf10 gene (Klf10 KO) resulted in ultrastructure fiber disorganization and mitochondrial metabolism deficiencies, characterized by muscular hypertrophy. To determine the metabolic profile related to loss of Klf10 expression, we analyzed blood and soleus tissue using UHPLC-Mass Spectrometry. Metabolomics analyses on both serum and soleus revealed profound differences between wild-type (WT) and KO animals. Klf10 deficient mice exhibited alterations in metabolites associated with energetic metabolism. Additionally, chemical classes of aromatic and amino-acid compounds were disrupted, together with Krebs cycle intermediates, lipids and phospholipids. From variable importance in projection (VIP) analyses, the Warburg effect, citric acid cycle, gluconeogenesis and transfer of acetyl groups into mitochondria appeared to be possible pathways involved in the metabolic alterations observed in Klf10 KO mice. These studies have revealed essential roles for Klf10 in regulating multiple metabolic pathways whose alterations may underlie the observed skeletal muscle defects as well as other diseases.

2010 IEEE. Reprinted, with permission, from Sébastien Ménigot, Iulian Voicu, Anthony Novell, Melouka Elkateb Hachemi Amar and Jean-Marc Girault,Adaptive matched filters for contrast imaging, 2010 IEEE International Ultrasonics Symposium (IUS), 11---14 Oct. 2010. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of the Université François Rabelais de Tours' products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org.; International audience; The ultrasound (US) contrast imaging is a promising technique. Currently the scientific community of this field seeks US excitations which should make possible the optimization of the acoustic contrast. Two matched filters (MF) techniques are used to improve the image contrast. The first technique is an adaptive MF technique and the second is a RLS technique derived from identification theory. The system proposed is a close loop system which optimizes the power backscattered by microbubbles. After having transmit a first signal, the backscattered power is optimized by transmitting the matched filtered signal at each iteration. This process is iterated until convergence. Simulations are carried out for encapsulated microbubbles of 2 microns by considering the modified Rayleigh-Plesset equation for a 2.25 MHz transmitted frequency and for various pressure levels (20 kPa up to 420 kPa). In vitro, experiments are carried out by using two transducers a transducers which were placed perpendicularly. The signal was transmitted through a 2.25 MHz transducer. Responses of a 1/2000 diluted solution of SonoVue were measured by a 3.5 MHz transducer. Each experiment has been realized with three pressure levels (127, 244 and 370 kPa). We show through simulations and through in vitro experiments that our adaptive imaging technique gives in case of simulations a gain which can reach 12 dB compared to the traditional technique and for in vitro experiments, the MF gives a gain which can reach 4.5 dB whereas the MF derived from identification theory can reach 6 dB.

National audience; La détection des micro-emboles cérébraux est d'une importance cruciale pour prévenir les accidents vasculaires cérébraux ischémiques. Les techniques de détection standard implémentées dans la plupart des systèmes Doppler transcrâniens sont basées sur une détection énergétique à seuil constant. Ce seuil peut être réglé statistiquement dans une phase d'apprentissage précédent clinique. En supposant que le signal Doppler est cyclostationnaire, nous proposons une détection synchrone de rupture de modèles AR et GARCH. Ces techniques ont été comparées aux techniques existantes à partir de simulations et de signaux réels. Pour les simulations, la technique standard détecte 60% de micro-emboles alors que la meilleure technique que nous proposons détecte 97% de micro-emboles pour une probabilité de fausse alarme de 0%. Pour les signaux réels, la technique standard détecte 67% de micro-emboles alors que la meilleure de nos techniques détecte 100% des micro-emboles pour une fausse alarme de 0%. Ces techniques de détections de ruptures de modèles synchrones ouvrent de nouvelles pistes pour la détection temps réel des micro-emboles.

National audience; Conventionnellement, les systèmes d'imagerie de contraste ultrasonore utilisent une fréquence d'émission fixe. Cependant, le milieu perfusé (microbulles) change au cours du temps, et donc nous suggérons une excitation adaptative au cours du temps. Nous proposons une technique d'imagerie adaptative qui sélectionne la fréquence optimale d'émission pour maximiser le contraste. Deux algorithmes ont été proposés pour trouver une excitation ultrasonore pour laquelle la fréquence est optimale pour les microbulles. Les simulations ont été réalisées avec une microbulle encapsulée de 2 microns à partir de l'équation de Rayleigh-Plesset modifiée pour différents niveaux de pression (de 20 kPa à 420 kPa). In vitro, les expériences ont été menées en utilisant 2 transducteurs placés perpendiculairement. Le signal était transmit par un transducteur à 2,25 MHz, tandis que la réponse d'une solution de Sonovue\texttrademark~ diluée à 1/2000 était mesurée par un transducteur à 3,5 MHz. Chaque expérience a été réalisée avec 2 niveaux de pression (244 et 370 kPa). Nous montrons à travers les simulations et les expériences in vitro que notre technique adaptative donne 1) pour les simulations, un gain qui peut atteindre 9 dB comparée aux techniques traditionnelles de l'imagerie de contraste 2) pour les expériences in vitro un gain qui peut atteindre 14 dB. En proposant un système en boucle fermée qui adapte de lui-même la fréquence au milieu perfusé tout au long de l'examen, le système d'optimisation s'adapte de lui-même à la population de microbulles restantes, et donc permet une augmentation de 30% de la durée d'examen. La divergence entre les résultats expérimentaux et ceux de simulations est non-négligeable. Ces différences sont certainement dues à la simulation qui ne prend pas en compte les imperfections des transducteurs, l'atténuation, la diffraction et les effets de la propagation. Cependant, ces résultats sont encourageants et nous suggèrent de continuer dans cette voie.

International Congress on Ultrasonics, Santiago de Chile, January 2009; International audience; Introduction: Since the introduction of ultrasound (US) contrast imaging, the imaging systems use a fixed emitting frequency. However it is known that the insonified medium is time-varying and therefore an adapted time-varying excitation is expected. We suggest an adaptive imaging technique which selects the optimal transmit frequency that maximizes the acoustic contrast. Two algorithms have been proposed to find an US excitation for which the frequency was optimal with microbubbles. Methods and Materials: Simulations were carried out for encapsulated microbubbles of 2 microns by considering the modified Rayleigh-Plesset equation for 2 MHz transmit frequency and for various pressure levels (20 kPa up to 420kPa). In vitro experiments were carried out using a transducer operating at 2 MHz and using a programmable waveform generator. Contrast agent was then injected into a small container filled with water. Results and discussions: We show through simulations and in vitro experiments that our adaptive imaging technique gives: 1) in case of simulations, a gain of acoustic contrast which can reach 9 dB compared to the traditional technique without optimization and 2) for in vitro experiments, a gain which can reach 18 dB. There is a non negligible discrepancy between simulations and experiments. These differences are certainly due to the fact that our simulations do not take into account the diffraction and nonlinear propagation effects. Further optimizations are underway.

Conventionnal ultrasound contrast imaging systems use a fixed transmit frequency. However it is known that the insonified medium (microbubbles) is time-varying and therefore an adapted time-varying excitation is expected. We suggest an adaptive imaging technique which selects the optimal transmit frequency that maximizes the contrast tissue ratio (CTR). The method is proposed with the contrast imaging and the harmonic contrast imaging. Simulations were carried out for encapsulated microbubbles of 2µm-radius by considering the modified Rayleigh-Plesset equation for various pressure levels (80 kPa up to 420kPa). In vitro experiments have been carried out using using a 2.25 MHz transmitter transducer and using a programmable waveform. We show, through experiments, that our adaptive imaging technique increases the CTR of 2 dB compared to the standard method looking at the central frequency. By proposing a close loop system whose frequency adapts itself with the perfused media, throughout the examination, the optimization system adapt itself to the bubble population to seek the best trade-off between the bubble response and the transducer bandwidth.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy has been broadly used. However, no consensus has been achieved on the practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult patients. METHODS: An online anonymous questionnaire survey endorsed by 4 academic societies from America, Europe, mainland China, and Taiwan was administered from May to December 2019. Clinicians who had worked in adult ICUs for > 1 year and had used HFNC to treat patients within 30 days were included. RESULTS: A total of 2,279 participants clicked on the survey link, 1,358 respondents completed the HFNC section of the questionnaire, whereas 1,014 completed the whole survey. Postextubation hypoxemia and moderate hypoxemia were major indications for HFNC. The initial flow was mainly set at 40–50 L/min. Aerosol delivery via HFNC was used by 24% of the participants (248/1,014), 30% (74/248) of whom reported reducing flow during aerosol delivery. For the patients who required aerosol treatment during HFNC therapy, 40% of the participants (403/1,014) reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC (a method shown to reduce inhaled dose), whereas 33% (331/1,014) discontinued HFNC to use conventional aerosol devices. A vibrating mesh nebulizer was the most commonly used nebulizer (40%) and was mainly placed at the inlet of the humidifier. CONCLUSIONS: The clinical utilization of HFNC was variable, as were indications, flow settings, and criteria for adjustment. Many practices associated with concomitant aerosol therapy were not consistent with available evidence for optimal use. More efforts are warranted to close the knowledge gap.

International Federation for Medical and Biological Engineering copyright; International audience; Introduction: Since the introduction of ultrasound (US) contrast imaging, the imaging systems use a fixed emitting frequency. However it is known that the insonified medium is time-varying and therefore an adapted time-varying excitation is expected. We suggest an adaptive imaging technique which selects the optimal transmit frequency that maximizes the acoustic contrast. Two algorithms have been proposed to find an US excitation for which the frequency was optimal with microbubbles. Methods and Materials: Simulations were carried out for encapsulated microbubbles of 2 microns by considering the modified Rayleigh-Plesset equation for 2 MHz transmit fre-quency and for various pressure levels (20 kPa up to 420kPa). In vitro experiments were carried out using a transducer oper-ating at 2 MHz and using a programmable waveform genera-tor. Contrast agent was then injected into a small container filled with water. Results and discussions: We show through simulations and in vitro experiments that our adaptive imaging technique gives: 1) in case of simulations, a gain of acoustic contrast which can reach 9 dB compared to the traditional technique without optimization and 2) for in vitro experiments, a gain which can reach 18 dB. There is a non negligible discrepancy between simulations and experiments. These differences are certainly due to the fact that our simulations do not take into account the diffraction and nonlinear propagation effects. Further optimizations are underway.

© 2009 IEEE. Reprinted, with permission, from Sébastien Ménigot, Anthony Novell, Ayache Bouakaz and Jean-Marc Girault, Improvement of the power response in contrast imaging with transmit frequency optimization, 2009 IEEE International Ultrasonics Symposium (IUS), 20---23 Sept. 2009. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of the Université François Rabelais de Tours' products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org.; International audience; Conventionnal ultrasound contrast imaging systems use a fixed transmit frequency. However it is known that the insonified medium (microbubbles) is time-varying and therefore an adapted time-varying excitation is expected. We suggest an adaptive imaging technique which selects the optimal transmit frequency that maximizes the contrast tissue ratio (CTR). Two algorithms have been proposed to find an US excitation for which the frequency has been optimal with microbubbles. Simulations were carried out for encapsulated microbubbles of 2µm-radius by considering the modified Rayleigh-Plesset equation for a 2.25MHz transmitted frequency and for various pressure levels (20 kPa up to 420kPa). In vitro experiments have been carried out using a 2.25 MHz transducer and using a programmable waveform generator. Responses of a 1/2000 blood mimicking fluid-diluted solution of Sonovue(TM) were measured by a 3.5 MHz transducer. We show through simulations that our adaptive imaging technique allows to reduce the transmit maximal pressure. As for in vitro experiments the CTR can reach 10 dB. By proposing a close loop system whose frequency adapts itself with the perfused media, throughout the examination, the optimization system adapt itself to the remaining bubbles population thus allowing an increase of the 30\% examination duration.

© 20009 IEEE. Reprinted, with permission, from S. Ménigot, L. Dreibine, N. Meziati and J.-M. Girault, Automatic detection of microemboli by means of a synchronous linear prediction technique, 2009 IEEE International Ultrasonics Symposium (IUS), 20---23 Sept. 2009. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of the Université François Rabelais de Tours' products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org.; International audience; Detection of microemboli is of great clinical importance to prevent cerebro-vascular events and to identify the causes of such events. As standard detection techniques implemented in the most commonly used systems cannot detect all of microemboli events whose energy is lower than the systolic energy, new techniques are proposed. By assuming that the Doppler signal is cyclostationary, we hypothesize that energy is statistically periodic. Furthermore, we hypothesis that embolic signals are unpredictable. Hence, the joint use of synchronous and linear prediction techniques could detect very small microemboli. If we periodically take and compare the values of the energy of the prediction error (or autoregressive parameters) at different time points in the cardiac cycle, we can therefore detect the presence of non-periodic events such as microemboli. In our study, we tested and compared our new technique to the standard technique (Fourier) using simulated and in vivo signals from patients with stenosis of high degrees of severity. From simulations, the standard automatic technique detected 60% of microemboli detected by our gold standard technique (audible detection and sonogram visualization) whereas the synchronous linear prediction technique detects 97% (the false alarm rate being set at 0%). From clinic examinations, the standard automatic technique only detects 67% of microemboli detected by our gold standard technique whereas the synchronous linear prediction technique detected 100%. This study demonstrates that our new technique detects microemboli up to now not identified by classical methods. Large microemboli are all detected, but small microemboli are only detected with our new technique. This latter technique opens up new prospects to detect small emboli, despite the need for further studies to incorporate ''on line'' technique.

National audience; L'imagerie de contraste, Doppler ou échographique, est un outil diagnostique qui est devenu aujourd'hui un système incontournable. Pendant presque un demi-siècle les principes fondateurs des systèmes Doppler ou échographiques n'ont pas beaucoup évolué. Pourtant, depuis plus d'une dizaine d'année les chercheurs du monde entier essaient de faire naître une nouvelle façon d'explorer les tissus biologique : c'est l'imagerie US codée adaptative. Les chercheurs imaginent de nouveaux systèmes d'imagerie fondés non plus sur la transmission de simples séries d'impulsions ultrasonores mais plutôt sur la transmission d'ondes dites intelligentes qui s'adaptent au fur et à mesure de l'examen clinique. L'innovation réside en fait en deux étapes. La première consiste à envoyer des ondes exploratrices qui, en sondant le milieu exploré, s'imprègnent des secrets les plus intimes de ce dernier. En disséquant les ondes renvoyées par le milieu exploré, le système extrait d'importantes informations qui, dans un second temps, serviront d'ingrédients à la constitution d'une nouvelle onde adaptée à l'objectif à atteindre c'est-à-dire imager le milieu exploré avec le meilleur contraste. Les futurs systèmes d'imagerie US ne seront plus des systèmes dits non bouclés, mais ils seront en boucle fermée assurant ainsi une prise en compte instantanée de l'évolution temporelle du milieu perfusé.

Objective\ud \ud Current concepts highlight the neurological and psychological heterogeneity of functional/dissociative seizures (FDS). However, it remains uncertain whether it is possible to distinguish between a limited number of subtypes of FDS disorders. We aimed to identify profiles of distinct FDS subtypes by cluster analysis of a multidimensional dataset without any a priori hypothesis.\ud \ud \ud \ud Methods\ud \ud We conducted an exploratory, prospective multicenter study of 169 patients with FDS. We collected biographical, trauma (childhood and adulthood traumatic experiences), semiological (seizure characteristics), and psychopathological data (psychiatric comorbidities, dissociation, and alexithymia) through psychiatric interviews and standardized scales. Clusters were identified by the Partitioning Around Medoids method. The similarity of patients was computed using Gower distance. The clusters were compared using analysis of variance, chi-squared, or Fisher exact tests.\ud \ud \ud \ud Results\ud \ud Three patient clusters were identified in this exploratory, hypothesis-generating study and named on the basis of their most prominent characteristics:\ud \ud 1. A “No/Single Trauma” group (31.4%), with more male patients, intellectual disabilities, and nonhyperkinetic seizures, and a low level of psychopathology;\ud \ud 2. A “Cumulative Lifetime Traumas” group (42.6%), with clear female predominance, hyperkinetic seizures, relatively common comorbid epilepsy, and a high level of psychopathology; and\ud \ud 3. A “Childhood Traumas” group (26%), commonly with comorbid epilepsy, history of childhood sexual abuse (75%), and posttraumatic stress disorder, but also with a high level of anxiety and dissociation.\ud \ud Significance\ud \ud Although our cluster analysis was undertaken without any a priori hypothesis, the nature of the trauma history emerged as the most important differentiator between three common FDS disorder subtypes. This subdifferentiation of FDS disorders may facilitate the development of more specific therapeutic programs for each patient profile.

International audience; Background: The purpose of this study is to assess the psychometric properties of the French version of the Positivity scale (P scale), a self-report measure of positivity, which is the tendency to view and address life and experience with a positive outlook. Positivity is seen as a latent factor underlying multiple cognitive concepts such as self-esteem, life satisfaction, and optimism. Methods: We recruited 666 volunteers (540 women and 126 men). They completed the P scale online, as well as self-report measures of psychological well-being, self-esteem, satisfaction with life, general health, and personality dimensions. The study sample was randomly split into two subgroups , one used for exploratory factor analysis and the other for confirmatory factor analysis. Results: We found conflictual results related to the uni-dimensionality of the French version of the P scale. We found good internal consistency and high concurrent validity. Conclusion: The French version of the P scale demonstrated good psychometric qualities and is a reliable tool that can now be used by French researchers and clinicians to assess positivity.

International audience; Recent evidence suggests that the chimeric protein SETMAR is a factor of interest in cancer, especially in glioblastoma. However, little is known about the expression of this protein in glioblastoma tissues, and no study has been done to assess if SETMAR could be a prognostic and/or diagnostic marker of glioblastoma. We analyzed protein extracts of 47 glioblastoma samples coming from a local and a national cohort of patients. From the local cohort, we obtained localized biopsies from the central necrosis area, the tumor, and the perilesional brain. From the French Glioblastoma Biobank (FGB), we obtained three types of samples: from the same tumors before and after treatment, from long survivors, and from very short survivors. We studied the correlations between SETMAR amounts, clinical profiles of patients and other associated proteins (PTN, snRNP70 and OLIG2). In glioblastoma tissues, the shorter isoform of SETMAR (S-SETMAR) was predominant over the full-length isoform (FL-SETMAR), and the expression of both SETMAR variants was higher in the tumor compared to the perilesional tissues. Data from the FGB showed that SETMAR amounts were not different between the initial tumors and tumor relapses after treatment. These data also showed a trend toward higher amounts of S-SETMAR in long survivors. In localized biopsies, we found a positive correlation between good prognosis and large amounts of S-SETMAR in the perilesional area. This is the main result presented here: survival in Glioblastoma is correlated with amounts of S-SETMAR in perilesional brain, which should be considered as a new relevant prognosis marker.

International audience; Recent studies have demonstrated a new role for Klf10, a Krüppel-like transcription factor, in skeletal muscle, specifically relating to mitochondrial function. Thus, it was of interest to analyze additional tissues that are highly reliant on optimal mitochondrial function such as the cerebellum and to decipher the role of Klf10 in the functional and structural properties of this brain region. In vivo (magnetic resonance imaging and localized spectroscopy, behavior analysis) and in vitro (histology, spectroscopy analysis, enzymatic activity) techniques were applied to comprehensively assess the cerebellum of wild type (WT) and Klf10 knockout (KO) mice. Histology analysis and assessment of locomotion revealed no significant difference in Klf10 KO mice. Diffusion and texture results obtained using MRI revealed structural changes in KO mice characterized as defects in the organization of axons. These modifications may be explained by differences in the levels of specific metabolites (myo-inositol, lactate) within the KO cerebellum. Loss of Klf10 expression also led to changes in mitochondrial activity as reflected by a significant increase in the activity of citrate synthase, complexes I and IV. In summary, this study has provided evidence that Klf10 plays an important role in energy production and mitochondrial function in the cerebellum.

International audience; The psychoendocrine evaluation of lamb development has demonstrated that maternal deprivation and milk replacement alters health, behavior and endocrine profiles. While lambs are able to discriminate familiar and non-familiar conspecifics (mother or lamb), only lambs reared with their mother develop such clear social discrimination or preference. Lambs reared without mother display no preference for a specific lamb from its own group. Differences in exploratory and emotional behaviours between mother-reared and mother deprived lambs have also been reported. As these behavioural abilities are supported by the brain, we hypothesize that rearing with maternal deprivation and milk replacement leads to altered brain development and maturation. To test this hypothesis, we examined brain morphometric and microstructural variables extracted from in-vivo T1-weighted and diffusion-weighted magnetic resonance images acquired longitudinally (1 week, 1.5 months and 4.5 months of age) in mother-reared and mother-deprived lambs. From the morphometric variables the caudate nuclei volume was found to be smaller for mother-deprived than for mother-reared lambs. T1-weighted signal intensity and radial diffusivity were higher for mother-deprived than for mother-reared lambs in both the white and gray matters. The fractional anisotropy of the white matter was lower for mother-deprived than for mother-reared lambs. Based on these morphometric and microstructural characteristics we conclude that maternal deprivation delays and affects lamb brain growth and maturation.

International audience; The first access to N-1, N-4 disubstituted pyrrolo[2,3-d][1,2,3]triazoles is reported. The series were generated using a “one-pot” MCR, leading to a single regioisomer of the attempted heteroaromatic skeleton in good yields. Next, the functionalization of C-5 and C-6 positions was investigated. (Het)aryl groups were introduced at the C-5 and C-6 positions of the pyrrolo[2,3-d][1,2,3]triazoles using regioselective electrophilic brominations followed by Suzuki–Miyaura cross coupling reactions. Palladium-catalyzed cross-coupling conditions were optimized and a representative library of various boronic acids was employed to establish the scope and limitations of the method

Simple Summary Physical activity is increasingly incorporated in cancer patient health care as a strategy to improve survival outcomes. However, its effects on treatment efficiency remains unclear. The aim of our preclinical study is to evaluate whether access to a running wheel could enhance the response to radiotherapy in mice with prostate cancer. We observed that voluntary wheel running (VWR) did not slow down tumor growth but appeared to modulate some parameters related to tumor perfusion. However, this did not result in enhanced response to radiotherapy. To investigate whether the lack of benefits on tumor growth observed with VWR could be attributed to the choice of physical activity modality, we conducted additional experiments comparing the effects of treadmill running versus VWR in two different preclinical models of prostate cancer. Only treadmill running was able to slow down tumor growth. Hence, the anti-cancer effects of physical activity seem dependent on its modalities. Abstract Physical activity is increasingly recognized as a strategy able to improve cancer patient outcome, and its potential to enhance treatment response is promising, despite being unclear. In our study we used a preclinical model of prostate cancer to investigate whether voluntary wheel running (VWR) could improve tumor perfusion and enhance radiotherapy (RT) efficiency. Nude athymic mice were injected with PC-3 cancer cells and either remained inactive or were housed with running wheels. Apparent microbubble transport was enhanced with VWR, which we hypothesized could improve the RT response. When repeating the experiments and adding RT, however, we observed that VWR did not influence RT efficiency. These findings contrasted with previous results and prompted us to evaluate if the lack of effects observed on tumor growth could be attributable to the physical activity modality used. Using PC-3 and PPC-1 xenografts, we randomized mice to either inactive controls, VWR, or treadmill running (TR). In both models, TR (but not VWR) slowed down tumor growth, suggesting that the anti-cancer effects of physical activity are dependent on its modalities. Providing a better understanding of which activity type should be recommended to cancer patients thus appears essential to improve treatment outcomes.

International audience; Nonword repetition is a relevant task in clinical phonological assessment. However, few authors have considered the impact of syllable constituency on child performance in such task. In this study, we analyse the contribution of syllable constituency in nonword repetition through the validation of a new test (LITMUS-QU-NWR-EP) adapted to European Portuguese (EP). Two syllable structures were considered: lateral coda (both in word-medial and word-final position) and branching onsets (obstruent + lateral clusters). Results from typically developing children, aged 5 to 8 years, showed generalized difficulties in both structures, although codas were less problematic than branching onsets. Portuguese child performance contrasts with the data obtained for the French version of the instrument (LITMUS-QU-NWR-FR), given the overall lower performance found for EP, and the preference for codas over branching onsets, unlike attested for French children. A comparative analysis shows that nonword repetition difficulties in what concerns syllabic constituency may be language dependent. Clinical implications for EP are discussed.

International audience; Antibody-based therapeutics have become a major class of therapeutics with over 120 recombinant antibodies approved or under review in the EU or US. This therapeutic class has experienced a remarkable expansion with an expected acceleration in 2021-2022 due to the extraordinary global response to SARS-CoV2 pandemic and the public disclosure of over a hundred anti-SARS-CoV2 antibodies. Mainly delivered intravenously, alternative delivery routes have emerged to improve antibody therapeutic index and patient comfort. A major hurdle for antibody delivery and efficacy as well as the development of alternative administration routes, is to understand the different natural and pathological barriers that antibodies face as soon as they enter the body up to the moment they bind to their target antigen. In this review, we discuss the well-known and more under-investigated extracellular and cellular barriers faced by antibodies. We also discuss some of the strategies developed in the recent years to overcome these barriers and increase antibody delivery to its site of action. A better understanding of the biological barriers that antibodies have to face will allow the optimization of antibody delivery near its target. This opens the way to the development of improved therapy with less systemic side effects and increased patients' adherence to the treatment.

Stroke is the second leading cause of death worldwide. Existing therapies present limitations, and other therapeutic alternatives are sought, such as sonothrombolysis with microbubbles (STL). The aim of this study was to evaluate the change induced by STL with or without recombinant tissue-type plasminogen activator (rtPA) on the acoustic and elastic properties of the blood clot by measuring its sound speed (SoS) and shear wave speed (SWS) with high frequency ultrasound and ultrafast imaging, respectively. An in-vitro setup was used and human blood clots were submitted to a combination of microbubbles and rtPA. The results demonstrate that STL induces a raise of SoS in the blood clot, specifically when combined with rtPA (p &lt, 0.05). Moreover, the combination of rtPA and STL induces a hardening of the clot in comparison to rtPA alone (p &lt, 0.05). This is the first assessment of acoustoelastic properties of blood clots during STL. The combination of rtPA and STL induce SoS and hardening of the clot, which is known to impair the penetration of thrombolytic drugs and their efficacy.

The impact of a third dose of COVID-19 vaccine on antibody responses is unclear in immunocompromised patients. The objective of this retrospective study was to characterize antibody responses induced by a third dose of mRNA COVID-19 vaccine in 160 kidney transplant recipients and 20 patients treated for chronic lymphocytic leukemia (CLL). Prevalence of anti-spike IgG ≥ 7.1 and ≥ 30 BAU/mL after the third dose were 47% (75/160) and 39% (63/160) in kidney transplant recipients, and 57% (29/51) and 50% (10/20) in patients treated for CLL. Longitudinal follow-up identified a moderate increase in SARS-CoV-2 anti-spike IgG levels after a third dose of vaccine in kidney transplant recipients (0.19 vs. 5.28 BAU/mL, p = 0.03) and in patients treated for CLL (0.63 vs. 10.7 BAU/mL, p = 0.0002). This increase in IgG levels had a limited impact on prevalence of anti-spike IgG ≥ 30 BAU/mL in kidney transplant recipients (17%, 2/12 vs. 33%, 4/12, p = 0.64) and in patients treated for CLL (5%, 1/20 vs. 45%, 9/20, p = 0.008). These results highlight the need for vaccination of the general population and the importance of non-medical preventive measures to protect immunocompromised patients.

Summary Background Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. Methods In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov , NCT04325906 , NCT04347941 , NCT04358939 , NCT04395144 , NCT04391140 , and NCT04477655 . Findings Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75−0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62−0·91), and the HR for mortality was 0·87 (0·68−1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. Interpretation Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. Funding Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interregional, Appel d'Offre 2020, Groupement Interregional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion a Tours de la Reanimation Medicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.

International audience; Entecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present before treatment in patient #1. HBs Ag immune escape mutations were present before treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). These results provided a unique insight into the evolution of HBV quasispecies during entecavir treatment, addressing the whole HBV genome and not only the Pol/RT domain. Our results suggest that mutations selected outside of the Pol/RT domain could contribute to entecavir treatment failure, not by an increased level of resistance, but by an immune escape mechanism, in synergy with immunosuppressive drugs.