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Background People living with HIV (PLWH) have a higher risk of CAD. Whether coronary artery calcification (CAC) score could better stratify the CV risk remains debated in this middle age population. Purpose We conducted the French CAC score study to compare the CAC score between PLHIV and HIV− subjects at intermediate risk. Methods 689 subjects (257 PLHIV and 432 HIV−) were consecutively addressed for CV risk evaluation including CAC score assessment in 2 centers between 2013 and 2019. Subjects were included if they were 18 years'old or older, had no known cardiovascular disease and had a CAC score along with cardiometabolic assessment. Results The mean age of the cohort was 59.3 years ± 10.7 and predominantly male (54%). PLHIV were younger (55.8 years ± 9.1 vs 61.3±11.3, p50% was found (13% vs 8%, p=0.16). Concerning, CV risk estimation using 10-year ASCVD and HEART scores, we observed that the median ASCVD score was similar between PLHIV and HIV− group (10.7% vs 9.8, p=0.15) but that PLHIV had a higher HEART score (3.0% vs 2.0%, p Conclusion In this cohort of subjects at intermediate CV risk according to CV risk scores estimation (ASCVD or HEART scores), PLHIV had a similar prevalence of CAC = 0 and median CAC scores as compared to HIV− subjects despite a younger age (6 years). Longitudinal follow up will explore whether this similar CAC score evaluation will be translated into higher CV events. Funding Acknowledgement Type of funding sources: None.

Genetic diagnosis of familial hypercholesterolemia (FH) remains unexplained in 30 to 70% of patients after exclusion of monogenic disease. There is now a growing evidence that a polygenic burden significantly modulates LDL-cholesterol (LDL-c) concentrations. Several LDL-c polygenic risk scores (PRS) have been set up. However, the balance between their diagnosis performance and their practical use in routine practice is not clearly established. Consequently, we set up new PRS based on our routine panel for sequencing and compared their diagnostic performance with previously-published PRS. After a meta-analysis, four new PRS including 165 to 1633 SNP were setup using different softwares. They were established using two French control cohorts (MONA LISA n=1082 and FranceGenRef n=856). Then the explained LDL-c variance and the ability of each PRS to discriminate monogenic negative FH patients (M-) versus healthy controls were compared with 4 previously-described PRS in 785 unrelated FH patients. Between all PRS, the 165-SNP PRS developed with PLINK showed the best LDL-c explained variance (adjusted R²=0.19) and the best diagnosis abilities (AUROC=0.77, 95%CI=0.74-0.79): it significantly outperformed all the previously-published PRS (p1 × 10

Although sexual interest in children is a risk factor for recidivism of sexual offenses against children, there is a dearth of measures for assessing its current level in patients with pedophilic disorder. The objective was to develop the Pedophilic Fantasies, Desires, and Activities Questionnaire (PFDAQ) to assess the current level of sexual interest in patients with pedophilic disorder. In total, 57 patients with pedophilic disorder and 53 controls were recruited. In addition to the PFDAQ, participants were presented with other measures of sexual interest. PFDAQ scores were significantly higher in patients than in controls and were correlated with other measures of sexual interest. Three PFDAQ scores were correlated with a phallometric index of preference for children. These results suggest that the PFDAQ may be valid and potentially useful for assessing the current level of pedophilic attraction.

Introduction Smoking prevalence in the overall population in France was 27% in 2017. There are few data about smoking prevalence in hospital workers. The aim of this study was to assess prevalence of current smoking in student and staff populations at Lyon University Hospital. Secondary objectives were to identify main variables associated with current smoking and willingness to quit. Methods We designed a single center, cross-sectional survey, using printed questionnaires. During one day, all registered staff and students were surveyed. We used optical reading to extract information from questionnaires. We performed univariate and multivariate analysis adjusted on most relevant factors. Results We analyzed 9712 questionnaires. The participating rates were high: 40.6% in the student cohort and 51.5% in the staff cohort. The proportion of current cigarette users was 26% in students and 25% in staff. In multivariate analysis, current smoking was significantly associated with: younger age, male sex, occupation type (e.g. logistical staff, and paramedical students), overnight work, and e-cigarette use. Among smokers, 53% reported a willingness to quit. In multivariate analysis, number of quit attempts, and feeling symptoms from tobacco were associated with willingness to quit. Conclusions Current smoking is less frequent in our cohorts of hospital staff and students than in the general French population. However, there are deep disparities in current smoking prevalence underlining a heterogeneous population. Among smokers, the majority reported a willingness to quit and some predictive factors may help to target this audience.

Although structural and functional neuroimaging techniques have recently been used to investigate the mechanisms of sexual attraction to children, a hallmark of pedophilic disorder, the differences in the processing of child sexual stimuli between men attracted to children and those attracted to adults remain unclear. Here, our purpose was to identify through positron emission tomography the brain responses of 15 male outpatients with pedophilic disorder to validated visual sexual stimuli depicting children (VSSc) and to compare them with 15 male healthy controls matched for sexual orientation (to female or male adults), age, and handedness. The patients' sample comprised both offenders and non-offenders. In response to VSSc, the between-groups analysis showed that activation in the right inferior temporal cortex [Brodmann area (BA) 20] was lower in patients than in controls. Moreover, in patients but not in controls, the presentation of VSSc induced an activation in a more caudal region of the right inferior temporal gyrus (BA 37) and in the left middle occipital gyrus (BA 19). In addition, in patients the level of activation in the caudal right inferior temporal gyrus was positively correlated with ratings of sexual arousal elicited by VSSc, whereas this correlation was negative in BA 20. These results implicate the right inferior temporal gyrus as a possible candidate area mediating sexual arousal in patients with pedophilic disorder and suggest that two of its areas play opposite, i.e., activating and inhibitory, roles., Highlights • Images of children activate the pedophilic patients' right Brodmann area (BA) 37. • Images of children (IC) activate the pedophilic patients' left BA 19. • Right BA37 activation correlates with pedophilic patients' rating of sexual arousal. • IC induce lower right BA 20 activation in pedophilic patients than in controls.

Structural and functional neuroimaging techniques have recently been used to investigate the mechanisms of sexual attraction to children, a hallmark of pedophilic disorder, and have reported many contradictory or non-replicated findings. Here, our purpose was to identify through functional magnetic resonance imaging the brain responses of 25 male outpatients with pedophilic disorder to visual stimuli depicting children (VSc) and to compare them with 24 male healthy controls matched on sexual orientation (to female or male adults), age, and handedness. No region was differentially activated across the two groups in response to VSc. However, as shown by a random-effects statistical analysis (cluster-level pFWE-corrected \textless 0.05), in patients with pedophilia, but not in controls, the presentation of VSc induced a bilateral activation in the lateral occipital and temporal cortices, in particular in the right inferior temporal gyrus, as well as an activation in the declive of the cerebellar vermis. In addition, in patients the level of bilateral activation in the above-mentioned regions was positively correlated with ratings of perceived sexual arousal elicited by VSc. These results implicate these regions as possible candidate areas mediating sexual arousal in patients with pedophilic disorder.

Supplemental material, PFDAQ_supplementary_file_corrected for Development and Preliminary Validation of the Pedophilic Fantasies, Desires, and Activities Questionnaire by Serge Stoléru, Virginie Moulier and Véronique Fonteille in International Journal of Offender Therapy and Comparative Criminology

Resume La frequence elevee des agressions sexuelles sur enfants et la gravite des troubles psychiatriques qu’elles contribuent a provoquer justifient de mieux etudier les mecanismes de l’attirance sexuelle pedophile, afin d’ameliorer les approches therapeutiques et preventives. Les premiers travaux en neuroimagerie fonctionnelle suggerent que certaines regions cerebrales sont plus activees chez les patients pedophiles que chez des temoins sains en reponse a la presentation d’images non pornographiques representant des enfants. Ces regions comprennent le cervelet, le gyrus orbitaire anterieur droit, le gyrus frontal inferieur droit, le gyrus fusiforme gauche, le cortex cingulaire anterieur gauche, et l’insula droite et gauche. Inversement, en reponse a ces images, l’activation du gyrus temporal moyen droit est plus forte chez les temoins. Pour aider a interpreter ces resultats, nous presentons un modele neurophenomenologique de l’excitation sexuelle. Il est vraisemblable que les progres de l’etude de la pedophilie par la neuroimagerie fonctionnelle aboutiront a des resultats pertinents sur le plan des questions et des debats judiciaires. Ces etudes doivent etre mieux organisees grâce a la mise en place d’une plateforme consacree a la clinique et a la recherche dans ce domaine.

Intensity Modulated Radiotherapy (IMRT) is a high-precision radiotherapy technique based on the use of a multi-leaf collimator, placed at the output of the accelerator. The modulation is adapted to the patient's anatomical structures and obtained by leaves movement during the beam administration. To ensure that the delivered fluence is consistent with the expected one, a control is necessary. In clinical routine, this control isn't achieved on the patient, but on a phantom, before the beginning of the treatment New emerging solutions make possible an online control, done during the treatment of the patient. They can be divided into three classes: those which use data acquired by the accelerator, those which exploit the portal imager and those which use a dedicated detector placed at the exit of the head of the accelerator, upstream of the patient. The thesis work presented here relate to the development of a detector of this third class, Tradera (Transparent Detector for Radiotherapy). The choice was made to use a segmented plane ionization chamber.The first phase of the project was to design the detector thanks to studies made by Monte Carlo simulations. For this it was necessary to model the photon beam. The choice of a point source of photons, quick to set up, has been retained. The characteristics of the particles at the detector input obtained with our model were compared with those obtained with a more complex model: a phase space obtained from the database of the IAEA. Once the model validated, Geant4 code was used to size the various elements of our detector. A innovative geometry has been proposed. It consists in introducing material in the sensitive volume of the detector to limit the lateral travel of the electrons from the interaction of photons, and thus improve the spatial resolution of the detector. In practice, a checkerboard with plastic pads is introduced in the sensitive volume. The benefit of this solution has been shown by simulations.The second phase was to assess a prototype in a clinical beam with radiation equipment and test the performance of various associated acquisition electronics. For a long time, reading was made at the output of a single channel at a time. First, a picoammeter was used to measure the average output current. Then the ionization current has been studied at the time scale of a pulse of the beam, allowing the development of a charge preamplifier dedicated to our application. This charge preamplifier permit to know, for a single beam pulse, the electrical charge measured by one channel of the prototype with a uncertainty of 5%, and thus makes it possible to study the evolution of the charge pulse as a function of irradiation time. Once the choice of this readout electronics was validated, the charge preamplifier was realized in small series : the acquisition in multi-channels on an area of ​​3 cm square was possible. The first beam images could then be obtained for static and dynamic beam., La Radiothérapie Conformationnelle avec Modulation d'Intensité (RCMI), aussi dénommée IMRT, est une technique avancée de radiothérapie de haute précision qui repose sur l'utilisation d'un collimateur multi-lames, placé en sortie de l'accélérateur, dont les lames vont se déplacer pendant la séance d'irradiation afin de produire un faisceau d'intensité modulée, adaptée à la forme des structures anatomiques du patient. Un tel dispositif permet d'obtenir une répartition de dose homogène dans le volume cible et d'épargner au mieux les tissus sains environnants1, ouvrant la voie à l'escalade de dose et donc à l'amélioration des résultats thérapeutiques. Néanmoins, la mise en œuvre d'une telle technique nécessite la réalisation d'un contrôle du système de délivrance de la dose de manière à s'assurer que la fluence délivrée par l'appareil de traitement est bien conforme à la fluence attendue.

Introduction: An innovative Transparent Detector for Radiotherapy (TraDeRa) has been developed for radiotherapy quality assurance (QA). It consists in a pixelated matrix of ionization chambers with a patented electrodes design. Each electrode is connected to in-house designed specific integrated circuits, providing a map of beam intensity and shape, at the linac pulse-scale. The detector aims at real-time monitoring of modulated beam upstream to the patient during delivery sessions, with a field cover up to 40 × 40 cm2. The work described here was realized on a 1:4 scale prototype in order to evaluate the dynamic of measurements, to characterize the raDeRa ability for detecting leaf position errors and to determine the impact of the detector presence on the photon beam. Methods: An acquisition system without charges losses and an electronic calibration procedure were developed to homogenize the response of each electrode and associated readout channel, allowing significant reduction of acquisition biases. An analysis method which takes into account the statistical calibration and measurement errors provides the relevant intensity deviations between two accumulated images of different acquisitions. The measurements under irradiation were performed with a clinical 6 MV X-Ray beam and a low energy high intensity photon beam from the European Synchrotron Radiation Facility (ESRF). Dose calculations are performed with the Monte Carlo code PENELOPE, modeling the full accelerator head and the TraDeRa detector. Results: A 2% attenuation of the 6 MV beam was measured in the presence of TraDeRa and the preliminary simulation study showed no significant modification of the photon beam properties. TraDeRa detects error leaf position as small as 1 mm compared to reference field, for both static(about 10% of local over-response)and modulated fields(about 4% focal over-response, see annex). In addition, measurements are stable over a large dynamic range from low intensity signals, as inter-leaves leaks, to very high intensities as obtained on the medical beamline of ESRF (dose rate thousand times larger than that of a conventional clinical linac). Conclusions: The 1:4 version of TraDeRa shows promising results for IMRT QA, allowing pulse-scale monitoring of the beam and high sensitivity for errors detection. The attenuation seems small enough not to hinder the irradiation while keeping the beam upstream to the patient under constant control. Nevertheless, further simulations will be necessary to convert the signal response of TraDeRa to dose response. In terms of dynamic, the detector is operational for every radiotherapy treatments, including the FFF modes with high dose rates(up to 2400 MU/min).The different versions ofTraDeRa already led to two patents [1] and [2]. A final prototype under development will include 1600 independent electrodes, half of them forming a high resolution area centered on the beam axis. The power supply, acquisition systems and data transmission will be embedded on the device, removing all external dependency and improving the compactness of the whole system. References [1] Brevet FR N° 11/53254. [2] Brevet FR N° 13/54339.

Introduction: The group Developments and Application for Medicine of the LPSC, in collaboration with the Public Hospital of Grenoble, is developing the TraDeRa detector (Transparent Detector for Radiotherapy). This device includes an ionization chambers matrix and provides 2D signal maps for any irradiation field, upstream to the patient. Converting the detector's signal into dose in the patient is a challenge. To do so, Monte Carlo simulation is a powerful tool, and will give accurate results if correctly parameterized. The work described here focuses on the optimization of the treatment head simulation (especially on the target, the source of X-rays) and the determination of the correct nominal energy and radial distribution of electrons on the target. In order to calibrate the detector, one must reach a perfect agreement between the observables from the simulation and from the beam of our reference accelerator. Methods: The interactions of the electrons in the target are numerous and time consuming to simulate. A study was conducted on both parameters of different particles transport methods and variance reduction in PENELOPE Monte Carlo code, which remains a reference for electron transport for the considered energies [1]. We have optimized a set of parameters to keep a reasonable computation time without biasing the physical observables. The determination of the initial characteristics of the electron beam (nominal energy/radial distribution of electrons on the target) is done by trial and error process. Several simulations are performed at various energies and radial electron distributions. The dose deposited in a simulated water phantom is compared with the depth-dose curves and dose profiles acquired under irradiation. We propose two efficient methods of comparison, the calculation of the Kolmogorov-Smirnov test and an original extension with more sensitivity. Results: The set of optimized parameters provides an overall increase on the simulation efficiency of nearly 300%. The useful secondary particles generation rate (stored in the PSF) was also increased by about 250%. Determining the characteristics of the electron accelerator of our reference beam is ongoing, we currently have simulated three energies around 6 MeV. In the appendix are presented the results of two comparative tests for these three energies. These tests including measurement uncertainties are robust and will accurately lead to the beam nominal energy with only five simulated energy sets. To date, the simulation has been running for six months on the IN2P3 computing center. Conclusions: The developed statistical tests are robust and will allow us to accurately determine the characteristics of the beam by comparing the simulated and the measured depth-dose curves and dose profiles. We will then be able to validate the reference accelerator simulation and calibrate the detector in terms of dose. This will allow us to reconstruct the 3D dose matrix in water from upstream information collected on a TraDeRa simulated model.

National audience

In the last decade, planar patch-clamp (PPC) has emerged as an innovative technology allowing parallel recordings of cellular electrophysiological activity on planar substrates. If PPC is widely adopted by the pharmaceutical sector, it remains poorly extended to other areas (i.e. environment and safety organizations) probably because of the large, expensive and non-easily transportable format of those commercial equipments. The present work describes for the first time a new compact and transportable planar patch-clamp system (named Toxint’patch or TIP, for Toxin detection with integrated patch-clamp) focusing on environmental matters and meant to be used in coastal laboratories, for direct on-site monitoring of the seawater and shellfish quality. The TIP system incorporates silicon chips tailored to monitor cellular ionic currents from cultured cells stably expressing a phycotoxin molecular target. The functionality of this novel briefcase-sized PPC system is described in terms of fluidic control, electronic performances with amplifying and filtering boards and of user interface for data acquisition and control implemented on a computer.

In the last fifteen years, functional neuroimaging techniques have been used to investigate the neuroanatomical correlates of sexual arousal in healthy human subjects. In most studies, subjects have been requested to watch visual sexual stimuli and control stimuli. Our review and meta-analysis found that in heterosexual men, sites of cortical activation consistently reported across studies are the lateral occipitotemporal, inferotemporal, parietal, orbitofrontal, medial prefrontal, insular, anterior cingulate, and frontal premotor cortices as well as, for subcortical regions, the amygdalas, claustrum, hypothalamus, caudate nucleus, thalami, cerebellum, and substantia nigra. Heterosexual and gay men show a similar pattern of activation. Visual sexual stimuli activate the amygdalas and thalami more in men than in women. Ejaculation is associated with decreased activation throughout the prefrontal cortex. We present a neurophenomenological model to understand how these multiple regional brain responses could account for the varied facets of the subjective experience of sexual arousal. Further research should shift from passive to active paradigms, focus on functional connectivity and use subliminal presentation of stimuli.

Gonadotropin-releasing hormone (GnRH) agonists, such as leuprorelin, are recommended in the patients with pedophilia at highest risk of offending. However, the cerebral mechanisms of the effects of these testosterone-decreasing drugs are poorly known. This study aimed to identify changes caused by leuprorelin in a pedophilic patient’s brain responses to pictures representing children. Clinical, endocrine, and fMRI investigations were done of a man with pedophilia before leuprorelin therapy and 5 months into leuprorelin therapy. Patient was compared with an age-matched healthy control also assessed 5 months apart. Before therapy, pictures of boys elicited activation in the left calcarine fissure, left insula, anterior cingulate cortex, and left cerebellar vermis. Five months into therapy, all the above-mentioned activations had disappeared. No such activations and, consequently, no such decreases occurred in the healthy control. The results of this pilot study suggest that leuprorelin decreased activity in regions known to mediate the perceptual, motivational, and affective responses to visual sexual stimuli.

International audience

International audience; Planar patch-clamp is a two-dimensional variation of traditional patch-clamp. By contrast to classical glass micropipette, the seal quality of silicon patch-clamp chips (i.e. seal resistance and seal success rate) have remained poor due to the planar geometry and the nature of the substrate and thus partially obliterate the advantages related to planar patch-clamp. The characterization of physical parameters involved in seal formation is thus of major interest. In this paper, we demonstrate that the physical characterization of surfaces by a set of techniques (Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), surface energy (polar and dispersive contributions), drop angles, impedance spectroscopy, combined with a statistical design of experiments (DOE)) allowed us discriminating chips that provide relevant performances for planar patch-clamp analysis. Analyses of seal quality demonstrate that dispersive interactions and micropore size are the most crucial physical parameters of chip surfaces, by contrast to surface roughness and dielectric membrane thickness. This multi-scale study combined with electrophysiological validation of chips on a diverse set of cell-types expressing various ion channels (IRK1, hERG and hNa(v)1.5 channels) unveiled a suitable patch-clamp chip candidate. This original approach may inspire novel strategies for selecting appropriate surface parameters dedicated to biochips.