Advanced spectroscopic investigation of colour centres in LiF crystals irradiated with monochromatic hard x-rays.

Nominally-pure lithium fluoride (LiF) crystals were irradiated with monochromatic hard x-rays of energy 5, 7, 9 and 12 keV at the METROLOGIE beamline of the SOLEIL synchrotron facility, in order to understand the role of the selected x-ray energy on their visible photoluminescence (PL) response, which is used for high spatial resolution 2D x-ray imaging detectors characterized by a wide dynamic range. At the energies of 7 and 12 keV the irradiations were performed at five different doses corresponding to five uniformly irradiated areas, while at 5 and 9 keV only two irradiations at two different doses were carried out. The doses were planned in a range between 4 and 1.4 × 103Gy (10.5 mJ cm-3to 3.7 J cm-3), depending on the x-ray energy. After irradiation at the energies of 7 and 12 keV, the spectrally-integrated visible PL intensity of the F2and F3+colour centres (CCs) generated in the LiF crystals, carefully measured by fluorescence microscopy under blue excitation, exhibits a linear dependence on the irradiation dose in the investigated dose range. This linear behaviour was confirmed by the optical absorption spectra of the irradiated spots, which shows a similar linear behaviour for both the F2and F3+CCs, as derived from their overlapping absorption band at around 450 nm. At the highest x-ray energy, the average concentrations of the radiation-induced F, F2and F3+CCs were also estimated. The volume distributions of F2defects in the crystals irradiated with 5 and 9 keV x-rays were reconstructed in 3D by measuring their PL signal using a confocal laser scanning microscope operating in fluorescence mode. On-going investigations are focusing on the results obtained through thisz-scanning technique to explore the potential impact of absorption effects at the excitation laser wavelength.

Measuring the principal Hugoniot of inertial-confinement-fusion-relevant TMPTA plastic foams.

Wetted-foam layers are of significant interest for inertial-confinement-fusion capsules, due to the control they provide over the convergence ratio of the implosion and the opportunity this affords to minimize hydrodynamic instability growth. However, the equation of state for fusion-relevant foams are not well characterized, and many simulations rely on modeling such foams as a homogeneous medium with the foam average density. To address this issue, an experiment was performed using the VULCAN Nd:glass laser at the Central Laser Facility. The aim was to measure the principal Hugoniot of TMPTA plastic foams at 260mg/cm^{3}, corresponding to the density of liquid DT-wetted-foam layers, and their "hydrodynamic equivalent" capsules. A VISAR was used to obtain the shock velocity of both the foam and an α-quartz reference layer, while streaked optical pyrometry provided the temperature of the shocked material. The measurements confirm that, for the 20-120 GPa pressure range accessed, this material can indeed be well described using the equation of state of the homogeneous medium at the foam density.

The multi-faceted nature of 15 CFTR exonic variations: Impact on their functional classification and perspectives for therapy.

BACKGROUND: The majority of variants of unknown clinical significance (VUCS) in the CFTR gene are missense variants. While change on the CFTR protein structure or function is often suspected, impact on splicing may be neglected. Such undetected splicing default of variants may complicate the interpretation of genetic analyses and the use of an appropriate pharmacotherapy. METHODS: We selected 15 variants suspected to impact CFTR splicing after in silico predictions on 319 missense variants (214 VUCS), reported in the CFTR-France database. Six specialized laboratories assessed the impact of nucleotide substitutions on splicing (minigenes), mRNA expression levels (quantitative PCR), synthesis and maturation (western blot), cellular localization (immunofluorescence) and channel function (patch clamp) of the CFTR protein. We also studied maturation and function of the truncated protein, consecutive to in-frame aberrant splicing, on additional plasmid constructs. RESULTS: Six of the 15 variants had a major impact on CFTR splicing by in-frame (n = 3) or out-of-frame (n = 3) exon skipping. We reclassified variants into: splicing variants; variants causing a splicing defect and the impairment of CFTR folding and/or function related to the amino acid substitution; deleterious missense variants that impair CFTR folding and/or function; and variants with no consequence on the different processes tested. CONCLUSION: The 15 variants have been reclassified by our comprehensive approach of in vitro experiments that should be used to properly interpret very rare exonic variants of the CFTR gene. Targeted therapies may thus be adapted to the molecular defects regarding the results of laboratory experiments.

Cylindrical implosion platform for the study of highly magnetized plasmas at Laser MegaJoule.

Investigating the potential benefits of the use of magnetic fields in inertial confinement fusion experiments has given rise to experimental platforms like the Magnetized Liner Inertial Fusion approach at the Z-machine (Sandia National Laboratories) or its laser-driven equivalent at OMEGA (Laboratory for Laser Energetics). Implementing these platforms at MegaJoule-scale laser facilities, such as the Laser MegaJoule (LMJ) or the National Ignition Facility (NIF), is crucial to reaching self-sustained nuclear fusion and enlarges the level of magnetization that can be achieved through a higher compression. In this paper, we present a complete design of an experimental platform for magnetized implosions using cylindrical targets at LMJ. A seed magnetic field is generated along the axis of the cylinder using laser-driven coil targets, minimizing debris and increasing diagnostic access compared with pulsed power field generators. We present a comprehensive simulation study of the initial B field generated with these coil targets, as well as two-dimensional extended magnetohydrodynamics simulations showing that a 5 T initial B field is compressed up to 25 kT during the implosion. Under these circumstances, the electrons become magnetized, which severely modifies the plasma conditions at stagnation. In particular, in the hot spot the electron temperature is increased (from 1 keV to 5 keV) while the density is reduced (from 40g/cm^{3} to 7g/cm^{3}). We discuss how these changes can be diagnosed using x-ray imaging and spectroscopy, and particle diagnostics. We propose the simultaneous use of two dopants in the fuel (Ar and Kr) to act as spectroscopic tracers. We show that this introduces an effective spatial resolution in the plasma which permits an unambiguous observation of the B-field effects. Additionally, we present a plan for future experiments of this kind at LMJ.

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study.

BACKGROUND: Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. METHODS: We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. RESULTS: We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). CONCLUSION: Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach.

The field of noninvasive prenatal diagnosis (NIPD) has undergone significant progress over the last decade. Direct haplotyping has been successfully applied for NIPD of few single-gene disorders. However, technical issues remain for triplet-repeat expansions. The objective of this study was to develop an NIPD approach for couples at risk of transmitting dynamic mutations. This method includes targeted enrichment for linked-read libraries and targeted maternal plasma DNA sequencing. We also developed an innovative Bayesian procedure to integrate the Hoobari fetal genotyping model for inferring the fetal haplotype and the targeted gene variant status. Our method of directly resolving parental haplotypes through targeted linked-read sequencing was smoothly performed using blood samples from families with Huntington's disease or myotonic dystrophy type 1. The Bayesian analysis of transmission of parental haplotypes allowed defining the genotype of five fetuses. The predicted variant status of four of these fetuses was in agreement with the invasive prenatal diagnosis findings. Conversely, no conclusive result was obtained for the NIPD of fragile X syndrome. Although improvements should be made to achieve clinically acceptable accuracy, our study shows that linked-read sequencing and parental haplotype phasing can be successfully used for NIPD of triplet-repeat expansion diseases.Trial registration: NCT04698551_date of first registration: 07/01/2021.

Direct observations of pure electron outflow in magnetic reconnection.

Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.

Robustness of large-area suspended graphene under interaction with intense laser.

Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene.

Medical students' learning processes the first time they role-play in psychiatry: A grounded theory study.

BACKGROUND: Recent changes in psychiatric care and teaching that limit patient contact for medical students can be overcome in part by simulation-based education. Understanding the learning processes of medical students involved in psychiatric simulation-based programmes could usefully inform efforts to improve this teaching. This study explored the learning processes of medical students the first time they role-play in psychiatry. METHODS: We used constructivist grounded theory to analyse semi-structured interviews of 13 purposively sampled medical students and the six psychiatrists who trained them. To improve the triangulation process, the results of this analysis were compared with those of the analyses of the role-play video and the debriefing audio-tapes. RESULTS: Five organising themes emerged: improving the students' immediate perception of patients with mental disorders; cultivating clinical reasoning; managing affect; enhancing skills and attitudes and fostering involvement in learning psychiatry. CONCLUSION: Results suggest that psychiatric role-playing can improve students' progressive understanding of psychiatry through the development of intuition and by allaying affects. Emotional elaboration and student involvement appear to be key features.

Exploring the Atwood-number dependence of the highly nonlinear Rayleigh-Taylor instability regime in high-energy-density conditions.

We experimentally study the late-time, highly nonlinear regime of the Rayleigh-Taylor instability in a decelerating phase. A series of laser-driven experiments is performed on the LULI2000 laser, in which the initial Atwood number is varied by adjusting the decelerating medium density. The high-power laser is used in a direct drive configuration to put into motion a solid target. Its rear side, which initially possesses a two-dimensional machined sinusoidal perturbations, expands and decelerates into a foam leading to a Rayleigh-Taylor unstable situation. The interface position and morphology are measured by time-resolved x-ray radiography. We develop a simple Atwood-dependent model describing the motion of the decelerating interface, from which its acceleration history is obtained. The measured amplitude of the instability, or mixing zone width, is then compared with late-time acceleration-dependent Rayleigh-Taylor instability models. The shortcomings of this classical model, when applied to high-energy-density conditions, are shown. This calls into question their uses for systems, where a shock wave is present, such as those found in laboratory astrophysics or in inertial confinement fusion.

Inefficient Magnetic-Field Amplification in Supersonic Laser-Plasma Turbulence.

We report a laser-plasma experiment that was carried out at the LMJ-PETAL facility and realized the first magnetized, turbulent, supersonic (Ma_{turb}≈2.5) plasma with a large magnetic Reynolds number (Rm≈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 compared to its subsonic, incompressible counterpart.

Micron-scale phenomena observed in a turbulent laser-produced plasma.

Turbulence is ubiquitous in the universe and in fluid dynamics. It influences a wide range of high energy density systems, from inertial confinement fusion to astrophysical-object evolution. Understanding this phenomenon is crucial, however, due to limitations in experimental and numerical methods in plasma systems, a complete description of the turbulent spectrum is still lacking. Here, we present the measurement of a turbulent spectrum down to micron scale in a laser-plasma experiment. We use an experimental platform, which couples a high power optical laser, an x-ray free-electron laser and a lithium fluoride crystal, to study the dynamics of a plasma flow with micrometric resolution (~1µm) over a large field of view (>1 mm2). After the evolution of a Rayleigh-Taylor unstable system, we obtain spectra, which are overall consistent with existing turbulent theory, but present unexpected features. This work paves the way towards a better understanding of numerous systems, as it allows the direct comparison of experimental results, theory and numerical simulations.

Liquid Structure of Tantalum under Internal Negative Pressure.

In situ femtosecond x-ray diffraction measurements and ab initio molecular dynamics simulations were performed to study the liquid structure of tantalum shock released from several hundred gigapascals (GPa) on the nanosecond timescale. The results show that the internal negative pressure applied to the liquid tantalum reached -5.6 (0.8) GPa, suggesting the existence of a liquid-gas mixing state due to cavitation. This is the first direct evidence to prove the classical nucleation theory which predicts that liquids with high surface tension can support GPa regime tensile stress.

Bremsstrahlung cannon design for shock ignition relevant regime.

We report on the optimization of a BremsStrahlung Cannon (BSC) design for the investigation of laser-driven fast electron populations in a shock ignition relevant experimental campaign at the Laser Megajoule-PETawatt Aquitaine Laser facility. In this regime with laser intensities of 1015 W/cm2-1016 W/cm2, fast electrons with energies ≤100 keV are expected to be generated through Stimulated Raman Scattering (SRS) and Two Plasmon Decay (TPD) instabilities. The main purpose of the BSC in our experiment is to identify the contribution to x-ray emission from bremsstrahlung of fast electrons originating from SRS and TPD, with expected temperatures of 40 keV and 95 keV, respectively. Data analysis and reconstruction of the distributions of x-ray photons incident on the BSC are described.

Neighborhood disorder predicts lower serum vitamin D levels in pregnant African American women: A pilot study.

Pregnant African American women are more likely to live in neighborhoods with more disorder (e.g., vacant housing, littler, crime) and to have vitamin D deficiency due to their darker skin pigmentation and poor production of vitamin D [25(OH)D] from ultraviolet rays. However, no study has examined the potential link between neighborhood disorder and 25(OH)D status in African American pregnant women. Forty-one pregnant African American women completed validated questionnaires about perceived neighborhood disorder (6 items; 3-point scale; range 6-18) and with concurrent serum levels of 25-hydroxyvitamin D [25(OH)D] assessed during pregnancy at 18-24 weeks gestation. Higher levels of perceived neighborhood disorder were associated with lower levels of serum 25(OH)D. Pregnant African American women who report higher disorder in their neighborhood may spend less time outside. Health care providers should include assessment of perceived neighborhood disorder. Future research needs to evaluate the relationships among neighborhood disorder and 25(OH)D levels among pregnant African American women.

Autosomal dominant SPG9: intrafamilial variability and onset during pregnancy.

INTRODUCTION: The ALDH18A1 gene, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS), is responsible for an autosomal recessive disease with severe developmental delay; more recently, ALDH18A1 was found to be responsible for SPG9, an autosomal dominant (AD) spastic paraplegia. CASE REPORT: We report a three-generation family with AD SPG9, initially suspected because of low citrulline on fasting plasma amino acid chromatography (AAC). Interestingly, in two patients, the spastic paraplegia appeared during pregnancy. One subject presented a severe childhood-onset form while another subject had a mild late-onset disease. CONCLUSION: The description of this family is of particular interest: it highlights the possibility of transient or permanent aggravation of spastic paraplegia due to SPG9 during pregnancy, suggesting a direct link between neurological symptoms and amino acid defect in a period of higher requirements and the potential benefit of amino acid supplementation; it underscores the value of plasma citrulline on fasting plasma AAC as a biomarker for this disease; it shows the variable expression of the disease.

Rayleigh-Taylor instability experiments on the LULI2000 laser in scaled conditions for young supernova remnants.

We describe a platform developed on the LULI2000 laser facility to investigate the evolution of Rayleigh-Taylor instability (RTI) in scaled conditions relevant to young supernova remnants (SNRs) up to 200 years. An RT unstable interface is imaged with a short-pulse laser-driven (PICO2000) x-ray source, providing an unprecedented simultaneous high spatial (24µm) and temporal (10 ps) resolution. This experiment provides relevant data to compare with astrophysical codes, as observational data on the development of RTI at the early stage of the SNR expansion are missing. A comparison is also performed with FLASH radiative magnetohydrodynamic simulations.

Collisionless Shocks Driven by Supersonic Plasma Flows with Self-Generated Magnetic Fields.

Collisionless shocks are ubiquitous in the Universe as a consequence of supersonic plasma flows sweeping through interstellar and intergalactic media. These shocks are the cause of many observed astrophysical phenomena, but details of shock structure and behavior remain controversial because of the lack of ways to study them experimentally. Laboratory experiments reported here, with astrophysically relevant plasma parameters, demonstrate for the first time the formation of a quasiperpendicular magnetized collisionless shock. In the upstream it is fringed by a filamented turbulent region, a rudiment for a secondary Weibel-driven shock. This turbulent structure is found responsible for electron acceleration to energies exceeding the average energy by two orders of magnitude.

Laser-driven shock compression of "synthetic planetary mixtures" of water, ethanol, and ammonia.

Water, methane, and ammonia are commonly considered to be the key components of the interiors of Uranus and Neptune. Modelling the planets' internal structure, evolution, and dynamo heavily relies on the properties of the complex mixtures with uncertain exact composition in their deep interiors. Therefore, characterising icy mixtures with varying composition at planetary conditions of several hundred gigapascal and a few thousand Kelvin is crucial to improve our understanding of the ice giants. In this work, pure water, a water-ethanol mixture, and a water-ethanol-ammonia "synthetic planetary mixture" (SPM) have been compressed through laser-driven decaying shocks along their principal Hugoniot curves up to 270, 280, and 260 GPa, respectively. Measured temperatures spanned from 4000 to 25000 K, just above the coldest predicted adiabatic Uranus and Neptune profiles (3000-4000 K) but more similar to those predicted by more recent models including a thermal boundary layer (7000-14000 K). The experiments were performed at the GEKKO XII and LULI2000 laser facilities using standard optical diagnostics (Doppler velocimetry and optical pyrometry) to measure the thermodynamic state and the shock-front reflectivity at two different wavelengths. The results show that water and the mixtures undergo a similar compression path under single shock loading in agreement with Density Functional Theory Molecular Dynamics (DFT-MD) calculations using the Linear Mixing Approximation (LMA). On the contrary, their shock-front reflectivities behave differently by what concerns both the onset pressures and the saturation values, with possible impact on planetary dynamos.