Upgrades to the gamma ray imager on DIII-D enabling access to high flux hard x-ray measurements during the runaway electron plateau phase (invited).

The Gamma Ray Imager (GRI) is a pinhole camera providing 2D imaging of MeV hard x-ray (HXR) bremsstrahlung emission from runaway electrons (REs) over the poloidal cross section of the DIII-D tokamak. We report a series of upgrades to the GRI expanding the access to RE scenarios from the diagnosis of a trace amount of REs to high flux HXR measurements during the RE plateau phase. We present the implementation of novel gamma ray detectors based on LYSO and YAP crystals coupled to multi-pixel photon counters, enabling a count rate in excess of 1 MHz. Finally, we highlight new insights into the RE physics discovered during the current quench and RE plateau phase experiments as the result of these upgrades.

Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence.

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.

Langmuir probe array for the small angle slot divertor in DIII-D.

The DIII-D small angle slot (SAS) divertor is designed for divertor physics studies with enhanced neutral confinement and special target geometries in a closed divertor. The closed nature of the SAS makes optical diagnostic measurements difficult, so a specially designed, multipurpose array of Langmuir probes has been implemented to study the plasma conditions in and around the slot. The probes are spaced to provide at least 2 mm resolution (shorter than the energy decay length) of the near scrape-off layer when mapped to the outer mid-plane. Due to space limitations at the bottom of the slot, a novel spring-loaded probe and tile design was developed to clamp several short rooftop probe tips and insulators to the cooled baseplate. Initial probe measurements revealed tile to tile edge shadowing, especially where magnetic field line surface angles were less than 1°. Additionally, it was found, using three Langmuir probes (at 90°, 180°, and 270°), that the strike point variation of ±5 mm radially around the torus was not well aligned with the circular slot geometry [Watkins et al., Nucl. Mater. Energy 18, 46 (2019)]. These issues were resolved by (1) designing tiles with all probes mounted near the tile center instead of near the edges and (2) aligning these new custom tiles to the measured strike point toroidal surface with a very accurate laser scanning alignment tool. Post-alignment Langmuir probe measurements and plasma behavior demonstrated close agreement at two separate toroidal locations that were 45° apart.

Optimizing the Detection of Subtle Insular Lesions on MRI When Insular Epilepsy Is Suspected.

Insular epilepsy is underdiagnosed and accounts for a number of failed operations. Identifying insular target lesions on MR imaging can help guide intracranial electroencephalography and improve the outcome of surgery. In this study, we present a novel method of exploring the insular region for subtle lesions on 3D MR imaging by MPR postprocessing of slices in oblique reference planes. Using this method, we retrospectively reviewed presurgical MRIs that were initially considered to have normal findings in 7 pediatric patients with intractable insular epilepsy. Insular epilepsy was confirmed in these patients on stereo-electroencephalography and histopathology. The MPR postprocessing method we describe helped detect subtle insular lesions in all 7 patients.

Thomson scattering measurements on DIII-D using in-vessel laser mirrors and lenses to diagnose a new divertor location.

Translatable in-vessel mirrors have enabled the DIII-D Thomson scattering system to diagnose the divertor plasma in high triangularity shaped plasmas. Previous divertor Thomson scattering measurements in DIII-D were restricted to spatial locations along a Nd:YAG laser beam that was directed through a vertical port. This only allowed measurements to be made in low triangularity shaped plasmas. The new mirrors re-route the laser underneath floor tiles to a position of smaller major radius as necessary for high triangularity plasmas. New in-vessel collection optics transmit scattered light from regions inaccessible to external lenses. Damage to mirrors and high stray light levels are challenges that were overcome to successfully make these measurements. Through the careful use of baffles and light shields, stray light leakage into polychromator detector channels was reduced to negligible levels, allowing temperature measurements below 1 eV. The system is described and the initial results presented.

The use of unfixed bone marrow trephines for multicolour flow cytometry.

An adequate bone marrow aspirate is essential for a rapid diagnosis of acute leukaemia by multicolour flow cytometry enabling the simultaneous assessment of multiple antigens on the cell surface as well as intracellular or nuclear ones. In the context of acute leukaemia, it is important to have a diagnosis of the blasts lineage as soon as possible to decide the appropriate treatment. This is sometimes delayed due to difficulties in obtaining a bone marrow aspirate due to a "dry tap". In this study we evaluated retrospectively cell markers results by flow cytometry of unfixed bone marrow trephines of 65 patients with leukaemia at diagnosis and including a few after treatment. Our aims were: 1) To compare cell markers results between bone marrow trephine (BMT) and bone marrow aspirate (BMA) 24 cases and BMT with peripheral blood (PB) 14 cases in paired samples to establish if they were reproducible with results of the unfixed bone marrow trephine biopsies. 2) To ascertain a precise diagnosis in 27 (42%) of the cases in which only a bone marrow trephine was available. We demonstrated that unfixed bone marrow trephine provides an adequate and representative cell suspension for flow cytometry and it is a powerful tool when no other material (bone marrow aspirate or peripheral blood) is available to make a rapid diagnosis. Furthermore when marrow aspirate or peripheral blood paired samples were available, flow cytometry results obtained were identical across all the sample types. Applicability to the clinical laboratory: We described a method to obtain a cell suspension from core biopsies that can easily be implemented routinely in a laboratory that performs diagnostic flow cytometry immunophenotyping. This method is simple, inexpensive and it doesn't require extra equipment.

Faraday-effect polarimeter diagnostic for internal magnetic field fluctuation measurements in DIII-D.

Motivated by the need to measure fast equilibrium temporal dynamics, non-axisymmetric structures, and core magnetic fluctuations (coherent and broadband), a three-chord Faraday-effect polarimeter-interferometer system with fast time response and high phase resolution has recently been installed on the DIII-D tokamak. A novel detection scheme utilizing two probe beams and two detectors for each chord results in reduced phase noise and increased time response [δb ∼ 1G with up to 3 MHz bandwidth]. First measurement results were obtained during the recent DIII-D experimental campaign. Simultaneous Faraday and density measurements have been successfully demonstrated and high-frequency, up to 100 kHz, Faraday-effect perturbations have been observed. Preliminary comparisons with EFIT are used to validate diagnostic performance. Principle of the diagnostic and first experimental results is presented.

Upgraded divertor Thomson scattering system on DIII-D.

A design to extend the unique divertor Thomson scattering system on DIII-D to allow measurements of electron temperature and density in high triangularity plasmas is presented. Access to this region is selectable on a shot-by-shot basis by redirecting the laser beam of the existing divertor Thomson system inboard - beneath the lower floor using a moveable, high-damage threshold, in-vacuum mirror - and then redirecting again vertically. The currently measured divertor region remains available with this mirror retracted. Scattered light is collected from viewchords near the divertor floor using in-vacuum, high temperature optical elements and relayed through the port window, before being coupled into optical fiber bundles. At higher elevations from the floor, measurements are made by dynamically re-focusing the existing divertor system collection optics. Nd:YAG laser timing, analysis of the scattered light spectrum via polychromators, data acquisition, and calibration are all handled by existing systems or methods of the current multi-pulse Thomson scattering system. Existing filtered polychromators with 7 spectral channels are employed to provide maximum measurement breadth (Te in the range of 0.5 eV-2 keV, ne in the range of 5 × 1018-1 × 1021 m3) for both low Te in detachment and high Te measurement up beyond the separatrix.

Gamma ray imager on the DIII-D tokamak.

A gamma ray camera is built for the DIII-D tokamak [J. Luxon, Nucl. Fusion 42, 614 (2002)] that provides spatial localization and energy resolution of gamma flux by combining a lead pinhole camera with custom-built detectors and optimized viewing geometry. This diagnostic system is installed on the outer midplane of the tokamak such that its 123 collimated sightlines extend across the tokamak radius while also covering most of the vertical extent of the plasma volume. A set of 30 bismuth germanate detectors can be secured in any of the available sightlines, allowing for customizable coverage in experiments with runaway electrons in the energy range of 1-60 MeV. Commissioning of the gamma ray imager includes the quantification of electromagnetic noise sources in the tokamak machine hall and a measurement of the energy spectrum of background gamma radiation. First measurements of gamma rays coming from the plasma provide a suitable testbed for implementing pulse height analysis that provides the energy of detected gamma photons.

Invasive EEG explorations.

The Wada test was adapted from the procedure described by Wada in 1964. It still has a role in the prognostic evaluation of memory disorders after mesial temporal lobectomy. The test consists of injecting a short-acting anesthetic into one hemisphere, under continuous EEG monitoring and during carotid catheterization, to verify the function of contralateral structures. Intracranial EEG recordings deliver signals with few artifacts, and which are quite specific of the zone explored. Three types of electrodes are in common use: (a) foramen ovale (FO) electrodes: electrodes can be inserted directly, without any stereotactic procedure, to provide easy and comparative EEG recordings of the lower and middle portions of the temporal lobe close to the hippocampus. These allow validation of the temporal lobe origin of seizures using FO electrodes recording coupled with scalp EEG; (b): subdural strip or grip electrodes. This relatively aggressive technique carries infectious and hemorrhagic risks and does not allow the exploration of deep cortical structures. However, it permits precise functional cortical mapping via electrical stimulation because of dense and regular positioning of electrodes over the cortical convexity; (c) stereotactically implanted depth electrodes (stereo-electroencephalography [SEEG]). Electrodes are individually planned and inserted within the brain parenchyma through small burr holes. This technique is less aggressive than subdural grid exploration. However it offers relatively limited spatial sampling that may be less well adapted to precise functional evaluation. It allows recording from deep cortical structures and can be argued to be the gold standard of presurgical EEG exploration.

Long-term EEG in children.

Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development.

[French guidelines on electroencephalogram]. / Recommandations françaises sur l'électroencéphalogramme.

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patient's bedside. Faced with the advances in knowledge, techniques and indications, the Société de Neurophysiologie Clinique de Langue Française (SNCLF) and the Ligue Française Contre l'Épilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines.

Outcome of surgery in children with focal cortical dysplasia younger than 5 years explored by stereo-electroencephalography.

PURPOSE: Focal cortical dysplasia (FCD) is the most frequent etiology for drug-resistant epilepsy in young children. Complete removal of the lesion is mandatory to cure the epilepsy. Stereo-EEG (SEEG) is an excellent method to delimitate the zone to be resected in older children and adults. We studied its feasibility in younger children. METHODS: We retrospectively studied 19 children under 5 years of age who underwent SEEG between January 2009 and December 2012 and were subsequently operated on. FCD was diagnosed in all. We reviewed magnetic resonance imaging (MRI), electrophysiological and clinical data, as well as postoperative seizure outcome. We also included fluoro-deoxyglucose positron emission tomography (FDG-PET) studies, which had been systematically performed before invasive recording in 16 of the 19 children. RESULTS: The mean patient's age at the time of SEEG was 38.6 months, and the mean age at seizure onset was 8 months. Three patients had normal MRI. No SEEG-associated complications occurred. We were able to delineate the epileptogenic zone in all children, and electrode stimulation localized the motor area when necessary (12 patients). Hypometabolic areas on FDG-PET included the epileptogenic zone in 13 of the 16 children, with a lobar concordance in 9 (56 %) and the same anatomical extent in 6 (38 %). Twelve children subsequently underwent focal or sublobar resection, six had multilobar resection, and one had hemispherotomy. The etiology was FCD type 2 in 15 and FCD type 1 or type 3 in three children. Eighty-four percent of our population have remained seizure-free at a mean follow-up of 29 months (12-48 months). CONCLUSION: Although children with FCD can successfully undergo resective surgery without invasive EEG, poor seizure semiology at this age inclines to perform SEEG when the dysplastic lesion is ill-defined and/or the electroclinical correlation is unclear. In cases with normal imaging as well as with suspected huge malformations, as was the case in 52 % of our patients, we consider it to be indispensable.

An upgrade of the magnetic diagnostic system of the DIII-D tokamak for non-axisymmetric measurements.

The DIII-D tokamak magnetic diagnostic system [E. J. Strait, Rev. Sci. Instrum. 77, 023502 (2006)] has been upgraded to significantly expand the measurement of the plasma response to intrinsic and applied non-axisymmetric "3D" fields. The placement and design of 101 additional sensors allow resolution of toroidal mode numbers 1 ≤ n ≤ 3, and poloidal wavelengths smaller than MARS-F, IPEC, and VMEC magnetohydrodynamic model predictions. Small 3D perturbations, relative to the equilibrium field (10(-5) < δB/B0 < 10(-4)), require sub-millimeter fabrication and installation tolerances. This high precision is achieved using electrical discharge machined components, and alignment techniques employing rotary laser levels and a coordinate measurement machine. A 16-bit data acquisition system is used in conjunction with analog signal-processing to recover non-axisymmetric perturbations. Co-located radial and poloidal field measurements allow up to 14.2 cm spatial resolution of poloidal structures (plasma poloidal circumference is ~500 cm). The function of the new system is verified by comparing the rotating tearing mode structure, measured by 14 BP fluctuation sensors, with that measured by the upgraded B(R) saddle loop sensors after the mode locks to the vessel wall. The result is a nearly identical 2/1 helical eigenstructure in both cases.

Insular and insulo-opercular epilepsy in childhood: an SEEG study.

PURPOSE: In recent years, there have been series analysing the electro-clinical correlations of insular epilepsy in adult populations. In contrast, the ictal semiology in children with insular epilepsy is poorly described. Considering that early and successful surgery may greatly improve the cognitive outcome and quality of life, it is worthwhile to deepen our knowledge of insular epilepsy in children. METHODS: We retrospectively evaluated ten children with drug-resistant focal insular epilepsy who had been consecutively explored with stereoelectroencephalography (SEEG), followed by individually tailored resective surgery that included part of the insula in all cases. A detailed anatomo-electro-clinical analysis of non-invasive EEG and SEEG data was performed. At least one of the electrodes explored the insular cortex. SEEG analysis confirmed that the insular cortex was included in the ictal onset zone. RESULTS: Epilepsy onset was mostly during the first year of life, characterized by subtle seizures as well as spasms and myoclonic seizures. Later on, neurovegetative signs and asymmetric tonic and hypermotor seizures (HMS) dominated the ictal semiology. The epileptogenic zone was frequently wider than insular with frontal and central predominance. In eight patients, the tailored resection included a lesion. In seven patients, an Engel class 1 outcome as well as neuropsychological and behavioural improvement was obtained. CONCLUSIONS: SEEG is feasible and useful in children with drug-resistant insular epilepsy which is often characterized by autonomic symptoms as the initial symptoms and should be suspected in cases with HMS, asymmetric tonic seizures and even asymmetric spasms. Early propagation is mostly frontal and central. Analysis of a larger population is required to refine these findings.

Swinging reciprocating Mach probes for the high field side scrape-off layer in DIII-D.

A new pair of in situ reciprocating Mach probes termed swing probes has been deployed on the DIII-D centerpost for the 2012 experimental campaign. When not deployed, the entire assembly is housed in a <5 cm space underneath the centerpost tiles. This design is unique in that the probe swings vertically through the edge plasma, taking measurements along a 180° arc with a 20 cm radius. The motion is powered by actuator coils that interact with the tokamak's magnetic field. Two electrodes maintain a Mach-pair orientation throughout the swing and provide measurements of saturation current, electron temperature, and parallel flow speeds up to the separatrix.

Soft x-ray array system with variable filters for the DIII-D tokamak.

Recent upgrades to the soft x-ray (SXR) array system on the DIII-D tokamak are described. The system consists of two 32-channel arrays at one toroidal location and three toroidally distributed 12-channel arrays. The 32-channel arrays have been completely rebuilt to allow the switching of SXR filters without breaking vacuum. The 12-channel arrays have had upgrades performed to detectors, view slits, and data acquisition. Absolute extreme ultraviolet (AXUV) photodiodes are used as detectors in all arrays, allowing detection of photons ranging in energy from 2 eV to 10 keV. In the fixed-filter arrays, 127 µm Be filters are used. In the variable-filter arrays, filter wheels are used to switch between five different possible pinhole/filter combinations.

Extended fast-ion D-alpha diagnostic on DIII-D.

A fast-ion deuterium-alpha (FIDA) diagnostic, first commissioned on DIII-D in 2005, relies on Doppler-shifted light from charge-exchange between beam neutrals and energetic ions. The second generation (2G) system was installed on DIII-D in 2009. Its most obvious improvement is the spatial coverage with 11 active in-beam and three passive off-beam views; the latter allows for simultaneous monitoring of the background signal. Providing extended coverage in fast-ion velocity space, the new views possess a more tangential component with respect to the toroidal field compared to their first generation counterparts. Each viewing chord consists of a bundle of three 1.5 mm core fibers to maximize light gathering. For greater throughput, fast f/1.8 optical components are used throughout. The signal is transmitted via fiber optics to a patch panel, so the user is able to choose the detector. FIDA was originally installed with a spectrometer and charge-coupled device (CCD) camera to monitor the full D(α) spectrum for two spatial views. 2G adds another spectrometer and CCD that monitor the blue-shifted wing for six spatial views at 1 kHz. In addition, a photomultiplier tube and fast digitizer provide wavelength-integrated signals at 1 MHz for eight spatial views.

High heat flux Langmuir probe array for the DIII-D divertor plates.

Two modular arrays of Langmuir probes designed to handle a heat flux of up to 25 MW/m(2) for 10 s exposures have been installed in the lower divertor target plates of the DIII-D tokamak. The 20 pyrolytic graphite probe tips have more than three times higher thermal conductivity and 16 times larger mass than the original DIII-D isotropic graphite probes. The probe tips have a fixed 12.5 degree surface angle to distribute the heat flux more uniformly than the previous 6 mm diameter domed collectors and a symmetric "rooftop" design to allow operation with reversed toroidal magnetic field. A large spring-loaded contact area improves heat conduction from each probe tip through a ceramic insulator into a cooled graphite divertor floor tile. The probe tips, brazed to molybdenum foil to ensure good electrical contact, are mounted in a ceramic tray for electrical isolation and reliable cable connections. The new probes are located 1.5 cm radially apart in a staggered arrangement near the entrance to the lower divertor pumping baffle and are linearly spaced 3 cm apart on the shelf above the in-vessel cryopump. Typical target plate profiles of J(sat), T(e), and V(f) with 4 mm spatial resolution are shown.