The Search Coil Magnetometer for THEMIS

International audienceTHEMIS instruments incorporate a tri-axial Search Coil Magnetometer (SCM) designed to measure the magnetic components of waves associated with substorm breakup and expansion. The three search coil antennas cover the same frequency bandwidth, from 0.1 Hz to 4 kHz, in the ULF/ELF frequency range. They extend, with appropriate Noise Equivalent Magnetic Induction (NEMI) and sufficient overlap, the measurements of the fluxgate magnetometers. The NEMI of the searchcoil antennas and associated pre-amplifiers is smaller than 0.76 pT/ p Hz at 10 Hz.The analog signals produced by the searchcoils and associated preamplifiers are digitized and processed inside the IDPU, together with data from the EFI instrument. Searchcoil telemetry includes waveform transmission, FFT processed data, and data from a filter bank. The frequency range covered in waveform depends on the available telemetry. The searchcoils and their three axis structures have been precisely calibrated in a quiet site, and the calibration of the transfer function is checked on board usually once per orbit. The tri-axial searchcoils implemented on the five THEMIS spacecraft are working nominally

MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial

Background: Diffuse midline gliomas (DMG) are characterized by a high incidence of H3 K27 mutations and poorer outcome. The HERBY trial has provided one of the largest cohorts of pediatric DMGs with available radiologic, histologic-genotypic, and survival data. / Purpose: To define MRI and molecular characteristics of DMG. / Materials and Methods: This study is a secondary analysis of a prospective trial (HERBY; ClinicalTrials.gov identifier, NCT01390948) undertaken between October 2011 and February 2016. Among 121 HERBY participants, 50 had midline nonpontine-based tumors. Midline high-grade gliomas were reclassified into DMG H3 K27 mutant, H3 wild type with enhancer of zest homologs inhibitory protein overexpression, epidermal growth factor receptormutant, or not otherwise stated. The epicenter of each tumor and other radiologic characteristics were ascertained from MRI and correlated with the new subtype classification, histopathologic characteristics, surgical extent, and outcome parameters. Kaplan-Meier curves and log-rank tests were applied to determine and describe survival differences between groups. / Results: There were 42 participants (mean age, 12 years ± 4 [SD]; 23 girls) with radiologically evaluable thalamic-based DMG. Eighteen had partial thalamic involvement (12 thalamopulvinar, six anteromedial), 10 involved a whole thalamus, nine had unithalamic tumors with diffuse contiguous extension, and five had bithalamic tumors (two symmetric, three partial). Twenty-eight participants had DMG H3 K27 mutant tumors; there were no differences in outcome compared with other DMGs (n = 4). Participants who underwent major debulking or total or near-total resection had longer overall survival (OS): 18.5 months vs 11.4 months (P = .02). Enrolled participants who developed leptomeningeal metastatic dissemination before starting treatment had worse outcomes (event-free survival, 2.9 months vs 8.0 months [P = .02]; OS, 11.4 months vs 18.5 months [P = .004]). / Conclusion: Thalamic involvement of diffuse midline gliomas ranged from localized partial thalamic to holo- or bithalamic with diffuse contiguous spread and had poor outcomes, irrespective of H3 K27 subtype alterations. Leptomeningeal dissemination and less than 50% surgical resection were adverse risk factors for survival. / Clinical trial registration no. NCT0139094

Phase II, open-label, randomized, multicenter trial (HERBY) of Bevacizumab in pediatric patients with newly diagnosed high-grade glioma

Purpose Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG). Methods The randomized, parallel group, multicenter, open-label HERBY trial (ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m² per day for 6 weeks; 4-week treatment break; then up to 12 3 28-day cycles of TMZ [cycle 1: 150 mg/m² per day, days 1 to 5; cycles 2 to 12: 200 mg/m² per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient. Results One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee–assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]). Conclusion Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies

Radiological evaluation of newly diagnosed non-brainstem pediatric high-grade glioma in the HERBY phase II trial

Purpose: The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma (HGG). The work presented here aims to correlate imaging characteristics and outcome measures with pathologic and molecular data.Experimental Design: Radiological, pathologic, and molecular data were correlated with trial clinical information to retrospectively re-evaluate event-free survival (EFS) and overall survival (OS).Results: One-hundred thirteen patients were randomized to the RT/TMZ arm (n = 54) or the RT/TMZ+BEV (BEV arm; n = 59). The tumor arose in the cerebral hemispheres in 68 patients (Cerebral group) and a midline location in 45 cases (Midline group). Pathologic diagnosis was available in all cases and molecular data in 86 of 113. H3 K27M histone mutations were present in 23 of 32 Midline cases and H3 G34R/V mutations in 7 of 54 Cerebral cases. Total/near-total resection occurred in 44 of 68 (65%) Cerebral cases but in only 5 of 45 (11%) Midline cases (P < 0.05). Leptomeningeal metastases (27 cases, 13 with subependymal spread) at relapse were more frequent in Midline (17/45) than in Cerebral tumors (10/68, P < 0.05). Mean OS (14.1 months) and EFS (9.0 months) in Midline tumors were significantly lower than mean OS (20.7 months) and EFS (14.9 months) in Cerebral tumors (P < 0.05). Pseudoprogression occurred in 8 of 111 (6.2%) cases.Conclusions: This study has shown that the poor outcome of midline tumors (compared with cerebral) may be related to (1) lesser surgical resection, (2) H3 K27M histone mutations, and (3) higher leptomeningeal dissemination

Etude et miniaturisation d'un analyseur basse fréquence destiné à la correction de l'effet Doppler à bord d'une sonde en mouvement rapide par rapport au milieu étudié (application à la mission "Solar Probe")

La mission "Solar Probe" (NASA) est une mission d'exploration de la couronne solaire qui combinera de l'imagerie à des mesures in situ de façon à étudier des phénomènes physiques tels que l'accélération du vent solaire et le chauffage de la couronne. Pour cela, les expériences embarquées doivent permettre de caractériser les ondes qui se propagent dans le plasma. Or, dans le cas des ondes basses fréquences, la vitesse de la sonde par rapport au plasma entraînera un décalage Doppler k. V important qu'il est indispensable d'évaluer pour caractériser correctement les ondes. Nous avons montré que le calcul de k. V et la correction des données, à partir de la mesure B et J dans le repère de la sonde et de l'utilisation de l'équation d'Ampère dans la limite basse fréquence, est possible. La validité de cette méthode a été démontrée, par des simulations, pour différentes combinaisons d'ondes planes. cependant, cette méthode n'est pas toujours utilisable, en particulier dans le cas d'ondes accompagnant la sonde (Vg [environ]Vsonde). Le faible taux de télémesure accordé rend intéressante l'utilisation d'un analyseur embarquée pour réaliser la correction Doppler. La faisabilité de cet analyseur a été étudiée au cours de la thèse. Cette étude comporte deux grands axes : la conception d'une maquette sur table et la miniaturisation d'un élément de la chaîne d'acquisition. L'utilisation du microprocesseur ADSP21060L a permis de réaliser un analyseur faible consommation (environ 1W) compatible avec les contraintes de la mission. Ce processeur n'étant pas qualifié pour les applications spatiales nous avons réalisé une pré-étude de tenue aux radiations dont les résultats sont favorables. La réalisation en technologie 3D d'un système de trois préamplificateurs et leur alimentation, associé à un tri-axes d'antennes magnétiques, a permis de réduire de 30/ la masse et le volume par rapport à la réalisation hybride utilisée précédemment sans dégradation de la sensibilté.VERSAILLES-BU Sciences et IUT (786462101) / SudocSudocFranceF

PDCT-01. BIOLOGICAL MEDICINE FOR DIFFUSE INTRINSIC PONTINE GLIOMAS ERADICATION (BIOMEDE): RESULTS OF THE THREE-ARM BIOMARKER-DRIVEN RANDOMIZED TRIAL IN THE FIRST 230 PATIENTS FROM EUROPE AND AUSTRALIA

International audienceAbstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating brain neoplasms. Despite 50 years of clinical trials, no improvement of survival has been observed and most children die within 2 years of diagnosis. Only radiotherapy transiently controls disease progression. METHODS/AIMS: BIOMEDE was conceived as a randomized multi-arm multi-stage program (drop-the-loser adaptive design). It started with an open-label phase-II trial comparing three drugs (everolimus, dasatinib, erlotinib) combined with irradiation, allocated according to the presence of their specific targets) with a planned sample size of 250 patients. A stereotactic biopsy was performed at diagnosis to centrally confirm the diagnosis of DIPG (presence of histone H3K27M mutation or loss of K27 trimethylation) and assess biomarkers/targets (PTEN-loss, EGFR-overexpression). Targeted therapies were started concomitantly with radiotherapy and were continued until disease progression. The main objective of the study was to compare the efficacy of randomized groups in terms of overall survival (OS). RESULTS At the 3rd interim analysis, based on 193 randomized patients among the 230 study patients, the IDMC concluded that the study was unlikely to meet its primary objective even if 250 patients were randomized. The median OS from the time of randomization was 10.9, 9.5 and 9 months for everolimus, dasatinib and erlotinib, respectively, which is comparable to historical controls. The median number of courses administered was 7, 5.5 and 6 respectively. Treatment was discontinued due to toxicity in 2%, 13%, and 15%, respectively. No biopsy-related death was reported and diagnostic yield was excellent, with only 5 non-informative biopsies. CONCLUSION BIOMEDE shows the feasibility of biologically-driven treatment in DIPG on a large international scale. Based on the better toxicity profile and the slightly better efficacy, although not statistically significant, the steering committee proposed that everolimus should be used as the control arm for the next step, BIOMEDE 2.0

Second generation of portable gamma camera based on Caliste CdTe hybrid technology

International audienceIn the framework of a national funded program for nuclear safety, a first prototype of portable gamma camera was built and tested. It integrates a Caliste-HD CdTe-hybrid detector designed for space X-ray astronomy coupled with a new system-on-chip based acquisition system (FPGA and ARM microprocessor) and thermo-electrical coolers for a use at room temperature. The complete gamma part of the camera fits in a volume of for a mass lower than 1 kg and a power consumption lower than 10 W. Localization and spectro-identification of radionuclides in a contaminated scene were demonstrated during several test campaigns. A new generation of system is under development taking into account feedback experience from in-situ measurements and integrating a new generation of sensor cost-optimized by industrial applications called Caliste-O. Caliste-O holds a 16x16 pixel detector of 14x14 mm2 and 2 mm thick with 8 full-custom front-end IDeF-X HD ASICs. Two prototypes were fabricated and tested. The paper will present the results of in-situ measurements with the first gamma camera, the spectroscopic performance of Caliste-O and the design of the second generation of gamma camera which aims for real time imaging and spectro-identification