Neuropathology of wild-type and nef-attenuated T cell tropic simian immunodeficiency virus (SIVmac32H) and macrophage tropic neurovirulent SIVmac17E-Fr in cynomolgus macaques

The neuropathology of simian immunodeficiency (SIV) infection in cynomolgus macaques (Macaca fascicularis) was investigated following infection with either T cell tropic SIVmacJ5, SIVmacC8 or macrophage tropic SIVmac17E-Fr. Formalin fixed, paraffin embedded brain tissue sections were analysed using a combination of in situ techniques. Macaques infected with either wild-type SIVmacJ5 or neurovirulent SIVmac17E-Fr showed evidence of neuronal dephosphorylation, loss of oligodendrocyte and CCR5 staining, lack of microglial MHC II expression, infiltration by CD4+ and CD8+ T cells and mild astrocytosis. SIVmacJ5-infected animals exhibited activation of microglia whilst those infected with SIVmac17E-Fr demonstrated a loss of microglia staining. These results are suggestive of impaired central nervous system (CNS) physiology. Furthermore, infiltration by T cells into the brain parenchyma indicated disruption of the blood brain barrier (BBB). Animals infected with the Δnef-attenuated SIVmacC8 showed microglial activation and astrogliosis indicative of an inflammatory response, lack of MHC II and CCR5 staining and infiltration by CD8+ T cells. These results demonstrate that the SIV infection of cynomolgus macaque can be used as a model to replicate the range of CNS pathologies observed following HIV infection of humans and to investigate the pathogenesis of HIV associated neuropathology

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Radiative shocks produced from spherical cryogenic implosions at the National Ignition Facility

Spherically expanding radiative shock waves have been observed from inertially confined implosion experiments at the National Ignition Facility. In these experiments, a spherical fusion target, initially 2 mm in diameter, is compressed via the pressure induced from the ablation of the outer target surface. At the peak compression of the capsule, x-ray and nuclear diagnostics indicate the formation of a central core, with a radius and ion temperature of ∼20 μm and ∼ 2 keV, respectively. This central core is surrounded by a cooler compressed shell of deuterium-tritium fuel that has an outer radius of ∼40 μm and a density of >500 g/cm3. Using inputs from multiple diagnostics, the peak pressure of the compressed core has been inferred to be of order 100 Gbar for the implosions discussed here. The shock front, initially located at the interface between the high pressure compressed fuel shell and surrounding in-falling low pressure ablator plasma, begins to propagate outwards after peak compression has been reached. Approximately 200 ps after peak compression, a ring of x-ray emission created by the limb-brightening of a spherical shell of shock-heated matter is observed to appear at a radius of ∼100 μm. Hydrodynamic simulations, which model the experiment and include radiation transport, indicate that the sudden appearance of this emission occurs as the post-shock material temperature increases and upstream density decreases, over a scale length of ∼10 μm, as the shock propagates into the lower density (∼1 g/cc), hot (∼250 eV) plasma that exists at the ablation front. The expansion of the shock-heated matter is temporally and spatially resolved and indicates a shock expansion velocity of ∼300 km/s in the laboratory frame. The magnitude and temporal evolution of the luminosity produced from the shock-heated matter was measured at photon energies between 5.9 and 12.4 keV. The observed radial shock expansion, as well as the magnitude and temporal evolution of the luminosity from the shock-heated matter, is consistent with 1-D radiation hydrodynamic simulations. Analytic estimates indicate that the radiation energy flux from the shock-heated matter is of the same order as the in-flowing material energy flux, and suggests that this radiation energy flux modifies the shock front structure. Simulations support these estimates and show the formation of a radiative shock, with a precursor that raises the temperature ahead of the shock front, a sharp μ m-scale thick spike in temperature at the shock front, followed by a post-shock cooling layer. © 2013 AIP Publishing LLC