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Cerebral sinus venous thrombosis (CSVT) is an uncommon disease that is usually treated with anticoagulation (heparin, low-molecular heparin, or vitamin K-antagonists). We compared treatment with edoxaban, an oral factor Xa-antagonist, that has not been approved in patients with CSVT, with enoxaparin, a well-established therapy, in a rat model of CSVT. Fifty male Wistar rats were randomized into 5 groups (10 animals each) and subjected to aluminum chloride (AlCl3)-induced thrombosis of the superior sagittal sinus (SSS) or sham procedure. Animals with thrombosis of the SSS were treated with edoxaban, enoxaparin, or placebo. Diagnostic workup included neurological examination, MRI imaging, MR-flow measurements of the SSS, and immunohistochemical staining. Neurological examination revealed no differences between treatment groups. Seven days after initial thrombosis, flow in the SSS was lower in the active treatment group as compared to sham-operated animals (p < 0.05). Flow in the SSS in the active treatment groups (edoxaban 1 h prior to thrombosis: 0.16 cm/s ± 0.06 cm/s; edoxaban 6 h after thrombosis: 0.13 cm/s ± 0.05 cm/s; enoxaparin: 0.13 cm/s ± 0.04 cm/s; placebo: 0.07 cm/s ± 0.02 cm/s) was higher as compared to placebo (p < 0.05), but there were no differences between the active treatment groups (p > 0.05). Immunohistochemical staining showed no differences in the actively treated animals. Edoxaban proved to be similar to enoxaparin in a model of experimental AlCl3-induced CSVT. [ABSTRACT FROM AUTHOR]

The overall goal of the indirect-drive inertial confinement fusion [1] tuning campaigns [2] is to maximize the probability of ignition by experimentally correcting for likely residual uncertainties in the implosion and hohlraum physics [3] used in our radiation-hydrodynamic computational models, and by checking for and resolving unexpected shot-to-shot variability in performance [4]. This has been started successfully using a variety of surrogate capsules that set key laser, hohlraum and capsule parameters to maximize ignition capsule implosion velocity, while minimizing fuel adiabat, core shape asymmetry and ablator-fuel mix.

Experiments conducted at the National Ignition Facility using shaped laser pulses with more than 1 MJ of energy have demonstrated the ability to control the implosion symmetry under ignition conditions. To achieve thermonuclear ignition, the low mode asymmetries must be small to minimize the size of the hotspot. The symmetry tuning experiments use symmetry capsules, “symcaps”, which replace the DT fuel with an equivalent mass of CH to emulate the hydrodynamic behavior of an ignition capsule. The x-ray self-emission signature from gas inside the capsule during the peak compression correlates with the surrounding hotspot shape. By tuning the shape of the self-emission, the capsule implosion symmetry can be made to be “round.” In the experimental results presented here, we utilized crossbeam energy transfer [S. H. Glenzer, et al., Science 327, 1228 (2010)] to change the ratio of the inner to outer cone power inside the hohlraum targets on the NIF. Variations in the ratio of the inner cone to outer cone power affect the radiation pattern incident on the capsule modifying the implosion symmetry.

HYBRID-E is an inertial confinement fusion implosion design that increases energy coupled to the hot spot by increasing the capsule scale in cylindrical hohlraums while operating within the current experimental limits of the National Ignition Facility. HYBRID-E reduces the hohlraum scale at a fixed capsule size compared to previous HYBRID designs, thereby increasing the hohlraum efficiency and energy coupled to the capsule, and uses the cross-beam energy transfer (CBET) to control the implosion symmetry by operating the inner (23° and 30°) and outer (44° and 50°) laser beams at different wavelengths (Δ λ > 0). Small case to capsule ratio designs can suffer from insufficient drive at the waist of the hohlraum. We show that only a small amount of wavelength separation between the inner and outer beams (Δ λ 1–2 Å) is required to control the symmetry in low-gas-filled hohlraums (0.3 mg/cm3 He) with enough drive at the waist of the hohlraum to symmetrically drive capsules 1180 μm in outer radius. This campaign is the first to use the CBET to control the symmetry in 0.3 mg/cm3 He-filled hohlraums, the lowest gas fill density yet fielded with Δ λ > 0. We find a stronger sensitivity of hot spot P2 in μm per Angstrom (40–50 μm/Å wavelength separation) than observed in high-gas-filled hohlraums and previous longer pulse designs that used a hohlraum gas fill density of 0.6 mg/cm3. There is currently no indication of transfer roll-off with increasing Δ λ , indicating that even longer pulses or larger capsules could be driven using the CBET in cylindrical hohlraums. We show that the radiation flux symmetry is well controlled during the foot of the pulse, and that the entire implosion can be tuned symmetrically in the presence of the CBET in this system, with low levels of laser backscatter out of the hohlraum and low levels of hot electron production from intense laser–plasma interactions. Radiation hydrodynamic simulations can accurately represent the early shock symmetry and be used as a design tool, but cannot predict the late-time radiation flux symmetry during the peak of the pulse, and semi-empirical models are used to design the experiments. Deuterium–tritium (DT)-layered tests of 1100 μm inner radius implosions showed performance close to expectations from simulations at velocities up to ∼360 km/s, and record yields at this velocity, when increasing the DT fuel layer thickness to mitigate hydrodynamic mixing of the ablator into the hot spot as a result of defects in the ablator. However, when the implosion velocity was increased, mixing due to these defects impacted performance. The ratio of measured to simulated yield for these experiments was directly correlated with the level of observed mixing. These simulations suggest that reducing the mixing, e.g., by improving the capsule defects, could result in higher performance. In addition, future experiments are planned to reduce the coast time at this scale, delay between the peak compression and the end of the laser, to increase the hot spot convergence and pressure. To reduce the coast time by several hundred ps compared to the 1100 μm inner radius implosions, HYBRID-E has also fielded 1050 μm inner radius capsules, which resulted in higher hot spot pressure and a fusion energy yield of ∼170 kJ. [ABSTRACT FROM AUTHOR]

In the article, the authors present their Ability to Self-Administer Medication in Non-Demented In-Hospital Patients (ABLYMED) study on the issues and challenges in the self management of medication by elderly patients like medication errors and drug safety. Also cited are the importance of correct medication administration in achieving the goals of treatment, and the complexities of pharmacotherapy in older patients.

Areal density non-uniformities seeded by time-dependent drive variations and target imperfections in Inertial Confinement Fusion (ICF) targets can grow in time as the capsule implodes, with growth rates that are amplified by instabilities. Here, we report on the first measurements of the perturbations on the density and areal density profiles induced by the membranes used to hold the capsule within the hohlraum in indirect drive ICF targets. The measurements are based on the reconstruction of the ablator density profiles from 2D radiographs obtained using pinhole imaging coupled to area backlighting, as close as 150 ps to peak compression. Our study shows a clear correlation between the modulations imposed on the areal density and measured neutron yield, and a 3× reduction in the areal density perturbations comparing a high-adiabat vs. low-adiabat pulse shape. [ABSTRACT FROM AUTHOR]

Progress toward ignition at the National Ignition Facility (NIF) has been focused on furthering the understanding of implosion performance. Implosion performance depends on the capsule fuel shape, on higher mode asymmetries that may cause hydrodynamic instabilities to quench ignition, on time-dependent asymmetries introduced by the hohlraum target, and on ablator performance. Significant findings in each of these four areas is reported. These investigations have led to improved in-flight capsule shape, a demonstration that a capsule robust to mix can generate high levels of neutrons (7.7 × 1014), hohlraum modifications that should ultimately provide improved beam propagation and better laser coupling, and fielding of capsules with high-density carbon (HDC) ablators. A capsule just fielded with a HDC ablator and filled with DT gas generated a preliminary record level of neutrons at 1.6 × 1015, or 5 kJ of energy. Future plans include further improvements to fuel shape and hohlraum performance, fielding robust capsules at higher laser power and energy, and tuning the HDC capsule. A capsule with a nanocrystalline diamond (HDC) ablator on a DT ice layer will be fielded at NIF later this year. [ABSTRACT FROM AUTHOR]

Ignition of an inertial confinement fusion (ICF) target depends on the formation of a central hot spot with sufficient temperature and areal density. Radiative and conductive losses from the hot spot can be enhanced by hydrodynamic instabilities. The concentric spherical layers of current National Ignition Facility (NIF) ignition targets consist of a plastic ablator surrounding a thin shell of cryogenic thermonuclear fuel (i.e., hydrogen isotopes), with fuel vapor filling the interior volume [S. W. Haan et al., Phys. Plasmas 18, 051001 (2011)]. The Rev. 5 ablator is doped with Ge to minimize preheat of the ablator closest to the DT ice caused by Au M-band emission from the hohlraum x-ray drive [D. S. Clark et al., Phys. Plasmas 17, 052703 (2010)]. Richtmyer-Meshkov and Rayleigh-Taylor hydrodynamic instabilities seeded by high-mode () ablator-surface perturbations can cause Ge-doped ablator to mix into the interior of the shell at the end of the acceleration phase [B. A. Hammel et al., Phys. Plasmas 18, 056310 (2011)]. As the shell decelerates, it compresses the fuel vapor, forming a hot spot. K-shell line emission from the ionized Ge that has penetrated into the hot spot provides an experimental signature of hot-spot mix. The Ge emission from tritium-hydrogen-deuterium (THD) and deuterium-tritium (DT) cryogenic targets and gas-filled plastic-shell capsules, which replace the THD layer with a mass-equivalent CH layer, was examined. The inferred amount of hot-spot-mix mass, estimated from the Ge K-shell line brightness using a detailed atomic physics code [J. J. MacFarlane et al., High Energy Density Phys. 3, 181 (2006)], is typically below the 75-ng allowance for hot-spot mix [S. W. Haan et al., Phys. Plasmas 18, 051001 (2011)]. Predictions of a simple mix model, based on linear growth of the measured surface-mass modulations, are consistent with the experimental results. [ABSTRACT FROM AUTHOR]

DT neutron yield (Yn), ion temperature (Ti), and down-scatter ratio (dsr) determined from measured neutron spectra are essential metrics for diagnosing the performance of inertial confinement fusion (ICF) implosions at the National Ignition Facility (NIF). A suite of neutron-time-of-flight (nTOF) spectrometers and a magnetic recoil spectrometer (MRS) have been implemented in different locations around the NIF target chamber, providing good implosion coverage and the complementarity required for reliable measurements of Yn, Ti, and dsr. From the measured dsr value, an areal density (ρR) is determined through the relationship ρRtot (g/cm2) = (20.4 ± 0.6) × dsr10-12 MeV. The proportionality constant is determined considering implosion geometry, neutron attenuation, and energy range used for the dsr measurement. To ensure high accuracy in the measurements, a series of commissioning experiments using exploding pushers have been used for in situ calibration of the as-built spectrometers, which are now performing to the required accuracy. Recent data obtained with the MRS and nTOFs indicate that the implosion performance of cryogenically layered DT implosions, characterized by the experimental ignition threshold factor (ITFx), which is a function of dsr (or fuel ρR) and Yn, has improved almost two orders of magnitude since the first shot in September, 2010. [ABSTRACT FROM AUTHOR]

The change in the power balance, temporal dynamics, emission weighted size, temperature, mass, and areal density of inertially confined fusion plasmas have been quantified for experiments that reach target gains up to 0.72. It is observed that as the target gain rises, increased rates of self-heating initially overcome expansion power losses. This leads to reacting plasmas that reach peak fusion production at later times with increased size, temperature, mass and with lower emission weighted areal densities. Analytic models are consistent with the observations and inferences for how these quantities evolve as the rate of fusion self-heating, fusion yield, and target gain increase. At peak fusion production, it is found that as temperatures and target gains rise, the expansion power loss increases to a near constant ratio of the fusion self-heating power. This is consistent with models that indicate that the expansion losses dominate the dynamics in this regime.

Although cellular prion protein (PrP(c)) has been suggested to have physiological roles in neurogenesis and angiogenesis, the pathophysiological relevance of both processes remain unknown. To elucidate the role of PrP(c) in post-ischemic brain remodeling, we herein exposed PrP(c) wild type (WT), PrP(c) knockout (PrP-/-) and PrP(c) overexpressing (PrP+/+) mice to focal cerebral ischemia followed by up to 28 days reperfusion. Improved neurological recovery and sustained neuroprotection lasting over the observation period of 4 weeks were observed in ischemic PrP+/+ mice compared with WT mice. This observation was associated with increased neurogenesis and angiogenesis, whereas increased neurological deficits and brain injury were noted in ischemic PrP-/- mice. Proteasome activity and oxidative stress were increased in ischemic brain tissue of PrP-/- mice. Pharmacological proteasome inhibition reversed the exacerbation of brain injury induced by PrP-/-, indicating that proteasome inhibition mediates the neuroprotective effects of PrP(c). Notably, reduced proteasome activity and oxidative stress in ischemic brain tissue of PrP+/+ mice were associated with an increased abundance of hypoxia-inducible factor 1α and PACAP-38, which are known stimulants of neural progenitor cell (NPC) migration and trafficking. To elucidate effects of PrP(c) on intracerebral NPC homing, we intravenously infused GFP(+) NPCs in ischemic WT, PrP-/- and PrP+/+ mice, showing that brain accumulation of GFP(+) NPCs was greatly reduced in PrP-/- mice, but increased in PrP+/+ animals. Our results suggest that PrP(c) induces post-ischemic long-term neuroprotection, neurogenesis and angiogenesis in the ischemic brain by inhibiting proteasome activity.

Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment.

DT neutron yield (Y(n)), ion temperature (T(i)), and down-scatter ratio (dsr) determined from measured neutron spectra are essential metrics for diagnosing the performance of inertial confinement fusion (ICF) implosions at the National Ignition Facility (NIF). A suite of neutron-time-of-flight (nTOF) spectrometers and a magnetic recoil spectrometer (MRS) have been implemented in different locations around the NIF target chamber, providing good implosion coverage and the complementarity required for reliable measurements of Y(n), T(i), and dsr. From the measured dsr value, an areal density (ρR) is determined through the relationship ρR(tot) (g∕cm(2)) = (20.4 ± 0.6) × dsr(10-12 MeV). The proportionality constant is determined considering implosion geometry, neutron attenuation, and energy range used for the dsr measurement. To ensure high accuracy in the measurements, a series of commissioning experiments using exploding pushers have been used for in situ calibration of the as-built spectrometers, which are now performing to the required accuracy. Recent data obtained with the MRS and nTOFs indicate that the implosion performance of cryogenically layered DT implosions, characterized by the experimental ignition threshold factor (ITFx), which is a function of dsr (or fuel ρR) and Y(n), has improved almost two orders of magnitude since the first shot in September, 2010.