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Background The immune-checkpoint inhibitors (ICIs) announced a new era in cancer treatment allowing long-term survival in advanced cancers. However, immune related adverse events impose treatment limitations being one of the main challenges when dealing with ICI treated patients. Neurologic toxicities have unique presentations and can progress rapidly, requiring prompt recognition. Among them, ICI-related peripheral nerve disorders are highly heterogeneous, profoundly debilitating, and insufficiently explored. Material and Methods We reviewed the clinical and electrodiagnostic features of a retrospective cohort of patients hospitalized in our centre for ICI related neuropathies. We applied the EFNS 2021 electrodiagnostic criteria for neuropathies and we researched the outcome according to the treatment received. Results We included 16 patients: 4 men and 12 women, median age 61 years (31-72) treated by anti-PD1 monotherapy (10) or antiCTLA4-antiPD1 combination (6). Median delay from ICIs initiation to neuropathy symptoms was 58,5 days (4 cycles), it seemed lower in combination group (median 33,5 days vs 81,5 days in monotherapy patients p=0,02). Half of patients presented with concurrent non-neurological irAE. CSF was inflammatory in 56% of cases, pleocytosis was seen in 57% of these. Cranial nerve involvement was rare (3/16) the most frequent phenotype was demyelinating polyneuropathy fulfilling EFNS 2021 EMG criteria in 10 cases. The other 6 presented with non-length dependent sensory neuropathy, (3) dysautonomic neuropathy (1) or sensory motor neuropathy with incomplete EFNS 2021 EMG criteria (2). ICI treatment was stopped, and steroids were the first line of treatment for all patients. However, 12/16 patients received additional iv immunoglobulin. Supplementary immunomodulation (cyclophosphamide, tocilizumab) was required in 2 cases. 75% of patients improved within a median of 4.5 months, median decrease in mRS was 2 points. Noteworthy, the rechallenge by antiPD1 monotherapy was proposed in 4 patients with a single neuropathy relapse. Conclusion Our series expand the knowledge on the clinical and electrophysiological phenotype of ICI related neuropathies improving their recognition in clinical practice. Moreover, our findings argue for the benefit of adding iv immunoglobulin to steroids as a first line treatment for different phenotypes of ICI related neuropathies.

We detail results of an experiment performed at the Ligne d'Intégration Laser facility aimed at studying supersonic and diffusive radiation front propagation in low-density SiO2 aerogel (20 and 40 mg/cm3) enclosed in a gold tube, driven by thermal emission from a laser-heated spherical gold cavity. The evolution of the front is studied continuously by measuring its self-emission with a 1D (one-dimensional) time-resolved soft x-ray imager. Measurement is performed along (through a 200- μm-wide observation slit) and at the exit of the tube giving access to the dynamics and the curvature of the front. Experimental results are then compared successfully to results from the 3D (three-dimensional) radiation hydrodynamics code TROLL, which shows that if continuous tracking of the front position is accessible with this experimental scheme, measurement of its maximum radiation temperature is on the contrary affected by radiation closure of the observation slit. 3D simulations also indicate that this effect can even be worsened if one includes pointing errors of the x-ray imager. Radiation temperature along the tube was then inferred by combining results from the imager to a wall shock breakout time measurement using a velocity interferometer system for any reflector and results from a broadband x-ray spectrometer used to determine the temperature at the exit of the tube. A decrease in the radiation temperature along the tube is observed, the decrease being more important for the higher SiO2 aerogel density.

International audience; We detail results of an experiment performed at the Laser Mégajoule (LMJ) facilityaimed at studying transition from supersonic radiation front to shock front in a lowdensity CHOBr foam enclosed in a plastic tube driven by thermal emission producedin a laser heated spherical gold cavity. Time resolved 2D hard x-ray radiographyimaging using a Sc source (photon energy at ~ 4.3 keV) is employed to measure thedensity perturbation front position, absorption, curvature and shocked materialcompression (defined as the compressed foam density normalized to its nominal value)from the supersonic to the subsonic regimes of propagation. Between these two regimeswhere compression goes from 1 (limited hydrodynamics) to 4 (strong shock formed), aquick increase of the foam compression is observed at the transition time tHS =6.75±0.75 ns, corresponding to the transient transonic regime (HS means“hydrodynamically separated” and refers to the instant when the shock and the radiationfront physically separate). This time is associated to a foam compression ratio of ~2and a Mach number of the slowing down front below M < 2. Experimental results aresuccessfully compared to 3D hydrodynamics simulations; comparisons never presentedfor that regime in past similar studies to our knowledge. Simulations show that thetransition time tHS is sensitive to the radiation closure of the tube entrance. This closure, which occurs in 3D, affects the amount of x-ray energy coupled from the laser heatedcavity to the CHOBr foam, and consequently the transient transonic regime dynamics.

We report on the performance of the highest radiant energy x-ray source at the LaserMegaJoule facility (LMJ) for testing material properties under irradiation. This radiation source was produced by the L-shell emission of xenon contained in a gas-pipe. The target was an epoxy ortho-cylinder tube with a diameter of 3 mm and a 50- μm thickness wall containing xenon gas at 1.2 atm. For this proof of principle shot, the LaserMegaJoule facility delivered a total energy of around 90 kJ of 351 nm laser and a total power of 30 TW. Thirty-two beams, divided into eight beamlets each, are arranged into two cones. The laser pulses were nearly flat, with a duration of 3 ns and a power range of 3.5–5 TW for each quadruplet. Two broadband spectrometers, DMX (DP4) and miniDMX (DP11), have been used to characterize the x-ray emission up to 10 keV. Radiant energy up to 0.5 kJ/sr has been recorded in the xenon L-shell band between 3 and 6 keV. This was the highest energy ever delivered for creating an x-ray source on the LMJ. Even though the target was axisymmetric, the strong asymmetric laser irradiation (nor axi or bottom/top symmetric) required full 3D radiation-hydrodynamic calculations to retrieve the radiant energy measured by broad band spectrometers. The main purpose of this work was to benchmark our 3D hydrorad code and the non-local thermodynamic equilibrium model by using newly developed x-ray spectrometers.

We report a laser-plasma experiment that was carried out at the LMJ-PETAL facility and realized the first magnetized, turbulent, supersonic plasma with a large magnetic Reynolds number ($\mathrm{Rm} \approx 45$) in the laboratory. Initial seed magnetic fields were amplified, but only moderately so, and did not become dynamically significant. A notable absence of magnetic energy at scales smaller than the outer scale of the turbulent cascade was also observed. Our results support the notion that moderately supersonic, low-magnetic-Prandtl-number plasma turbulence is inefficient at amplifying magnetic fields., 6 pages, 4 figures; supplemental information included (14 pages, 10 figures)

The effectiveness of a dome-shaped wall covered by a thin gold foil (hollow wall) [M. Vandenboomgaerde et al., Phys. Plasmas 25, 012713 (2018)PHPAEN1070-664X10.1063/1.5008669] in holding back the high-Z plasma expansion in a gas-filled hohlraum is demonstrated for the first time in experiments reproducing the irradiation conditions of indirect drive at the ignition scale. The setup exploits a 1D geometry enabling record of the complete history of the gold expansion for 8 ns by imaging its emission in multiple x-ray energy ranges featuring either the absorption zones or the thermal emission regions. The measured expansion dynamics is well reproduced by numerical simulations. This novel wall design could now be tailored for the megajoule scale to enable the propagation of the inner beams up to the equator in low gas-filled hohlraum thus allowing the fine-tuning of the irradiation symmetry on the timescale required for ignition.

The effectiveness of a dome-shaped wall covered by a thin gold foil (hollow wall) [M. Vandenboomgaerde et al., Phys. Plasmas 25, 012713 (2018)PHPAEN1070-664X10.1063/1.5008669] in holding back the high-Z plasma expansion in a gas-filled hohlraum is demonstrated for the first time in experiments reproducing the irradiation conditions of indirect drive at the ignition scale. The setup exploits a 1D geometry enabling record of the complete history of the gold expansion for 8 ns by imaging its emission in multiple x-ray energy ranges featuring either the absorption zones or the thermal emission regions. The measured expansion dynamics is well reproduced by numerical simulations. This novel wall design could now be tailored for the megajoule scale to enable the propagation of the inner beams up to the equator in low gas-filled hohlraum thus allowing the fine-tuning of the irradiation symmetry on the timescale required for ignition.

International audience; We present an experiment performed in 2016 at the LULI2000 laser facility in which X-ray and XUV absorption structures of nickel hot plasmas were measured simultaneously. Such experiments may provide stringent tests of the accuracy of plasma atomic-physics codes used to the modeling of plasmas close to local thermodynamic equilibrium. The experimental setup relies on a symmetric heating of the sample foil by two gold hohlraums in order to reduce the spatial gradients. The plasma conditions are characterized by temperatures between 10 and 20 eV and densities of the order of 10$^{−3}$ g/cm $^3$-10$^{−2}$ g/cm$^3$. For the X-ray part, we investigate the 2p-3d and 2p-4d transitions, and for the XUV part, we recorded the $\Delta$n = 0 (n = 3) transitions, which present a high sensitivity to plasma temperature. These latter transitions are of particular interest because, in mid-Z plasmas, they dominate the Planck and Rosseland mean opacities. Measured spectra are compared to calculations performed using the hybrid opacity code SCO-RCG and the Flexible Atomic Code (FAC). The influence of a spectator electron on the calculated spectra is analyzed using the latter code.

Implosion experiments of an inertial confinement fusion (ICF) target on the laser megajoule (LMJ) and the National Ignition Facility require, for certain designs, a precise timing coalescence of fo...

The advent of high-power lasers facilities such as the National Ignition Facility (NIF), and the Laser Megajoule (LMJ) in the near future, opens a new era in the field of High Energy Density Laboratory Astrophysics. These versatile laser facilities will provide unique platforms to study the rich physics of nonlinear and turbulent mixing flows. The extended laser pulse duration could be harnessed to accelerate targets over much larger distances and longer time periods than previously achieved. We report on the first results acquired on NIF with the ablative Rayleigh–Taylor Instability (RTI) platform. A 20-ns X-ray drive is tailored to accelerate planar modulated samples into the highly-nonlinear bubble merger regime. Based on the analogy between flames front and ablation front, highly nonlinear RTI measurements at ablation front can provide important insights into the initial deflagration stage of thermonuclear supernova of Type Ia. We also report on an innovative concept used to create even longer drive on multi-beam laser facilities. The multi-barrel hohlraum (Gattling Gun) approach consists, here, of three adjacent cavities, driven in succession in time. This novel concept has been validated on the Omega EP laser system. The three cavities were irradiated with three 6–10 ns pulse UV beams and a 30 ns, 90 eV X-ray radiation drive was measured with the time-resolved X-ray spectrometer μDMX. This concept is promising to investigate the pillar structures in the Eagle Nebula or for photoionization studies which require a steady light source of sufficient duration to recreate relevant physics.

The advent of high-power lasers facilities such as the National Ignition Facility (NIF), and Laser Megajoule (LMJ) in the near future opens a new era in the field of High Energy Density Laboratory Astrophysics. The LMJ, keystone of the French Simulation Program, is under construction at CEA/CESTA and will deliver 1.5 MJ with 176 beamlines. The first physics experiments on LMJ will be performed at the end of 2014 with 2 quadruplets (8 beams). The operational capabilities (number of beams and plasma diagnostics) will increase gradually during the following years. We describe the current status of the LMJ facility and the first set of diagnostics to be used during the commissioning phase and the first experiments. The PETAL project (PETawatt Aquitaine Laser), part of the CEA opening policy, consists in the addition of one short-pulse (500 fs to 10 ps) ultra-high-power, high-energy beam (a few kJ compressed energy) to the LMJ facility. PETAL is focalized into the LMJ target chamber and could be used alone or in combination with LMJ beams. In the later case, PETAL will offer a combination of a very high intensity multi-petawatt beam, synchronized with the nanosecond beams of the LMJ. PETAL, which is devoted to the academic research, will also extend the LMJ diagnostic capabilities. Specific diagnostics adapted to PETAL capacities are being fabricated in order to characterize particles and radiation yields that can be created by PETAL. A first set of diagnostics will measure the particles (protons/ions/electrons) spectrum (0.1–200 MeV range) and will also provide point projection proton-radiography capability. LMJ/PETAL, like previously the LIL laser [X. Julien et al., Proc. SPIE 7916 (2011) 791610], will be open to the academic community. Laboratory astrophysics experiments have already been performed on the LIL facility, as for example radiative shock experiments and planetary interiors equation of state measurements.

International audience; Ion stopping experiments in plasma for beam energies of few hundred keV per nucleon are of great interest to benchmark the stopping-power models in the context of inertial confinement fusion and high-energy-density physics research. For this purpose, a specific ion detector on chemical-vapor-deposition diamond basis has been developed for precise time-of-flight measurements of the ion energy loss. The electrode structure is interdigitated for maximizing its sensitivity to low-energy ions, and it has a finger width of 100 μm and a spacing of 500 μm. A short single α-particle response is obtained, with signals as narrow as 700 ps at full width at half maximum. The detector has been tested with α-particle bunches at a 500 keV per nucleon energy, showing an excellent time-of-flight resolution down to 20 ps. In this way, beam energy resolutions from 0.4 keV to a few keV have been obtained in an experimental configuration using a 100 μg/cm2 thick carbon foil as an energy-loss target and a 2 m time-of-flight distance. This allows a highly precise beam energy measurement of δE/E ≈ 0.04%–0.2% and a resolution on the energy loss of 0.6%–2.5% for a fine testing of stopping-power models.

Due to the iconic status of the pillars of the Eagle Nebula, this research will bring popular attention to plasma physics, HED laboratory physics, and fundamental science at NIF and other experimental facilities. The result will be to both to bring new perspectives to the studies of hydrodynamics in inertial confinement fusion and HED scenarios in general, and to promote interest in the STEM disciplines.

This research will; confirm the possibility of studying the structure and evolution of star-forming regions of molecular clouds in the laboratory; test the cometary model for the formation of the pillar structures in molecular clouds; assess the effect of magnetic fields on the evolution of structures in molecular clouds; and develop and demonstrate a new, long-duration (60-100 ns), directional source of x-ray radiation that can be used for the study of deeply nonlinear hydrodynamics, hydrodynamic instabilities that occur in the presence of directional radiation, shock-driven and radiatively-driven collapse of dense cores, and photoionization. Due to the iconic status of the pillars of the Eagle Nebula, this research will bring popular attention to plasma physics, HED laboratory physics, and fundamental science at NIF and other experimental facilities. The result will be to both to bring new perspectives to the studies of hydrodynamics in inertial confinement fusion and HED scenarios in general, and to promote interest in the STEM disciplines.

Introduction L’efficacite et la tolerance du facteur VII active recombinant (rFVIIa) sont reconnues chez les patients avec une hemophilie A acquise (HAA), mais des donnees detaillees sur le controle du saignement en pratique medicale sont limitees. Patients et methodes L’objectif de cette etude prospective, observationnelle, multicentrique, francaise (ACQUI-7) etait de renforcer les connaissances sur les differents types de saignements survenant chez des patients HAA (titre de l’auto-anticorps anti-FVIII > 1 UB ; taux de FVIII Les donnees ont ete collectees dans 20 centres de traitement de l’hemophilie ou departement de medecine interne entre 2010 et 2013. Apres inclusion pour prise en charge d’un episode hemorragique traite par rFVIIa en 1re ou 2nde intention, les patients etaient suivis pendant 1 an. Les modalites d’utilisation du rFVIIa etaient laissees au libre arbitre de l’investigateur. Resultats Vingt-sept patients (18 hommes), âges de 76 ans (± 14 DS) ont ete recrutes. Seize (59 %) patients avaient une HAA idiopathique, les autres avaient une pathologie associee possiblement liee a la survenue de HAA (5 une polyarthrite rhumatoide, 1 un lupus erythemateux systemique, 3 une pathologie tumorale active) et/ou des medicaments potentiellement inducteurs (betalactamines [2], clopidrogel [3]). Plus de la moitie des patients avaient une maladie ou des facteurs de risque cardiovasculaires. Vingt-sept saignements (89 % severes) ont ete traites avec rFVIIa, en premiere intention. Le saignement justifiant le traitement par rFVIIa etait musculaire (12), cutane (3), digestif (3), urinaire (2), pleural (2), retroperitoneal (2), oropharynge (1), articulaire (1) et post-extraction dentaire (1). Plus de 15 jours avant l’episode hemorragique a l’origine du diagnostic, 9 patients ont presente des saignements et principalement cutanes et/ou muqueux (7). Le delai median entre le diagnostic et le traitement etait de 1,5 jour. rFVIIa etait efficace dans 89 % des saignements. La dose initiale etait de 90,5 mg/kg [83,2 ; 100,0], la duree du traitement de 4 jours [2 ; 11] avec 12 [5 ; 21] injections et la dose cumulee de 0,90 mg/kg [0,48 ; 1,79] (mediane [Q1 ; Q3]). Le nombre median quotidien d’injections pendant les 4 premiers jours etait entre 2 et 3. L’utilisation du rFVIIa pour le traitement des saignements severes entre j1 (1er jour de traitement) et j4 sont presentees dans le Tableau 1 . Au cours du traitement, une modification de la dose et/ou frequence des injections etait realisee chez 19 patients avec une augmentation chez 6 patients et une diminution chez 16 patients. Aucun evenement indesirable grave, dont evenement thromboembolique, lie au rFVIIa n’a ete rapporte. Six deces sont survenus (septicemie, saignement, deterioration generale [1] , neoplasmes [1] ). Conclusion Ces donnees sont en accord avec celles des etudes EACH2, SACHA, pour le type de saignements traites et la prise en charge globale par rFVIIa (doses cumulees, nombre total d’injections, duree de traitement). ACQUI-7 apporte des informations complementaires sur l’utilisation quotidienne du rFVIIa dans l’hemophilie acquise.

X-ray transmission spectra of copper, nickel and aluminum laser produced plasmas were measured at the LULI2000 laser facility with an improved target design of indirect heating. Measurements were performed in plasmas close to local thermodynamic equilibrium at temperatures around 25 eV and densities between 10−3 g/cm3 and 10−2 g/cm3. This improved design provides several advantages, which are discussed in this paper. The sample is a thin foil of mid-Z material inserted between two gold cavities heated by two 300J, 2ω, nanosecond laser beams. A third laser beam irradiates a gold foil to create a spectrally continuous X-ray source (backlight) used to probe the sample. We investigate 2p–3d absorption structures in Ni and Cu plasmas as well as 1s–2p transitions in an additional Al plasma layer to infer the in-situ plasma temperature. Geometric and hydrodynamic calculations indicate that the improved geometry reduces spatial gradients during the transmission measurements. Experimental absorption spectra are in good agreement with calculations from the hybrid atomic physics code SCO-RCG.

The x-ray yields from laser-irradiated thin foils of iron, copper, zinc, and germanium have been measured in the soft and multi-keV x-ray ranges at the OMEGA laser at the Laboratory for Laser Energetics. The incident laser power had a pre-pulse to enhance the x-ray emission of a 1 ns flat-top main pulse. The experimental results have been compared with post-shot simulations performed with the two-dimensional radiation-hydrodynamics code FCI2. A new non-local thermodynamic equilibrium model, NOO-RAD, have been incorporated into FCI2. In this approach, the plasma ionization state is in-line calculated by the atomic physics NOHEL package. In the soft x-ray bands, both simulations using RADIOM [M. Busquet, Phys. Fluids B 5, 4191 (1993)] and NOO-RAD clearly over-predict the powers and energies measured by a broad-band spectrometer. In one case (the iron foil), the discrepancy between the measured and simulated x-ray output is nevertheless significantly reduced when NOO-RAD is used in the simulations. In the multi-keV x-ray bands, the simulations display a strong sensitivity to the coupling between the electron thermal conductivity and the NLTE models, and for some particular combinations of these, provide a close match to the measured emission. The comparison between the measured and simulated H-like to He-like line-intensity ratios deduced from high-resolution spectra indicates higher experimental electron temperatures were achieved, compared to the simulated ones. Measurements of the plasma conditions have been achieved using the Thomson-scattering diagnostic. The electron temperatures are found to range from 3 to 5 keV at the end of the laser pulse and are greater than predicted by the simulations. The measured flow velocities are in reasonable agreement with the calculated ones. This last finding gives us confidence in our numerical predictions for the plasma parameters, which are over that time mainly determined by hydrodynamics, such as the mass densities and the ion temperatures.

Experimental investigation of stimulated Raman (SRS) and Brillouin (SBS) scattering have been obtained at the Ligne-d'Integration-Laser facility (LIL, CEA-Cesta, France). The parametric instabilities (LPI) are driven by firing four laser beamlets (one quad) into millimeter size, gas-filled hohlraum targets. A quad delivers energy on target of 15 kJ at 3ω in a 6-ns shaped laser pulse. The quad is focused by means of 3ω gratings and is optically smoothed with a kinoform phase plate and with smoothing by spectral dispersion-like 2 GHz and/or 14 GHz laser bandwidth. Open- and closed-geometry hohlraums have been used, all being filled with 1-atm, neo-pentane (C5H12) gas. For SRS and SBS studies, the light backscattered into the focusing optics is analyzed with spectral and time resolutions. Near-backscattered light at 3ω and transmitted light at 3ω are also monitored in the open geometry case. Depending on the target geometry (plasma length and hydrodynamic evolution of the plasma), it is shown that, at maximu...