Neutralization of chemokines RANTES and MIG increases virus antigen expression and spinal cord pathology during Theiler's virus infection.

The role of chemokines during some viral infections is unpredictable because the inflammatory response regulated by these molecules can have two, contrasting effects-viral immunity and immunopathologic injury to host tissues. Using Theiler's virus infection of SJL mice as a model of this type of disease, we have investigated the roles of two chemokines-regulated on activation, normal T cell-expressed and secreted (RANTES) chemokine and monokine induced by IFN-gamma (MIG)-by treating mice with antisera that block lymphocyte migration. Control, infected mice showed virus persistence, mild inflammation and a small degree of demyelination in the white matter of the spinal cord at 6 weeks post-infection. Treatment of mice with RANTES antiserum starting at 2 weeks post-infection increased both viral antigen expression and the severity of inflammatory demyelination at 6 weeks post-infection. MIG antiserum increased the spread of virus and the proportion of spinal cord white matter with demyelination. Overall, viral antigen levels correlated strongly with the extent of pathology. At the RNA level, high virus expression was associated with low IL-2 and high IL-10 levels, and RANTES antiserum decreased the IL-2/IL-10 ratio. Our results suggest that RANTES and MIG participate in an immune response that attempts to restrict viral expression while limiting immunopathology and that anti-chemokine treatment poses the risk of exacerbating both conditions in the long term

Stroke saturation on a MEMS deformable mirror for woofer-tweeter adaptive optics

High-contrast imaging of extrasolar planet candidates around a main-sequence star has recently been realized from the ground using current adaptive optics (AO) systems. Advancing such observations will be a task for the Gemini Planet Imager, an upcoming "extreme" AO instrument. High-order "tweeter" and low-order "woofer" deformable mirrors (DMs) will supply a >90%-Strehl correction, a specialized coronagraph will suppress the stellar flux, and any planets can then be imaged in the "dark hole" region. Residual wavefront error scatters light into the DM-controlled dark hole, making planets difficult to image above the noise. It is crucial in this regard that the high-density tweeter, a micro-electrical mechanical systems (MEMS) DM, have sufficient stroke to deform to the shapes required by atmospheric turbulence. Laboratory experiments were conducted to determine the rate and circumstance of saturation, i.e. stroke insufficiency. A 1024-actuator 1.5-um-stroke MEMS device was empirically tested with software Kolmogorov-turbulence screens of r_0=10-15cm. The MEMS when solitary suffered saturation ~4% of the time. Simulating a woofer DM with ~5-10 actuators across a 5-m primary mitigated MEMS saturation occurrence to a fraction of a percent. While no adjacent actuators were saturated at opposing positions, mid-to-high-spatial-frequency stroke did saturate more frequently than expected, implying that correlations through the influence functions are important. Analytical models underpredict the stroke requirements, so empirical studies are important.Comment: 16 pages, 10 figure

Amplitude variations on the Extreme Adaptive Optics testbed

High-contrast adaptive optics systems, such as those needed to image extrasolar planets, are known to require excellent wavefront control and diffraction suppression. At the Laboratory for Adaptive Optics on the Extreme Adaptive Optics testbed, we have already demonstrated wavefront control of better than 1 nm rms within controllable spatial frequencies. Corresponding contrast measurements, however, are limited by amplitude variations, including those introduced by the micro-electrical-mechanical-systems (MEMS) deformable mirror. Results from experimental measurements and wave optic simulations of amplitude variations on the ExAO testbed are presented. We find systematic intensity variations of about 2% rms, and intensity variations with the MEMS to be 6%. Some errors are introduced by phase and amplitude mixing because the MEMS is not conjugate to the pupil, but independent measurements of MEMS reflectivity suggest that some error is introduced by small non-uniformities in the reflectivity

Effect of metabolic syndrome on mean pulmonary arterial pressures in patients with acute pulmonary embolism treated with catheter-directed thrombolysis

Background: Metabolic syndrome (MetS) has been associated with a procoagulant and hypofibrinolytic state. Current data exploring the role of MetS in venous thromboembolism (VTE) are limited. The objective was to measure the prevalence of MetS in patients with acute PE receiving catheter-directed thrombolysis (CDT) and to investigate its effect on mean pulmonary arterial pressure and overall treatment success. Methods: We used a 3-year prospective registry of ED patients with acute PE with severity qualifying for activation of a PE response team (PERT). All patients had CDT with catheter-measured mPAP and angiography. The presence or absence of MetS components were extracted from chart review based on the following criteria: 1. body mass index (BMI) >30 kg/m2; 2. diagnosed hypertension; 3. diabetes mellitus (including HbA1c >6.5%) and; 4. dyslipidemia (including triglycerides >150 mg/dL or high-density lipoprotein <40 mg/dL). Results: Of the 134 patients, 85% met the criteria for at least one of four MetS components, with obesity being most common, present in 71%. Results demonstrated a positive concordance between the number of criteria for MetS and MPAP, both pre- and post-fibrinolysis, as pressures tended to increase with each additional MetS criterion. Multivariate regression analysis determined age (-), BMI (+) and hypertension (+) to be significant independent predictor variables for mPAP. Conclusions: MetS was common in patients with more severe manifestations of PE and was associated with higher mPAP values both at diagnosis and following treatment with CDT

Re-emergence of Tobacco streak virus Infecting Soybean in the United States and Canada

Tobacco streak virus (TSV), an Ilarvirus, was first confirmed as a viral pathogen of tobacco in 1936 (Johnson 1936) and first reported in North American soybean in 1969 (Fagbenle and Ford 1970). TSV has a wide host range with strains able to infect at least 140 different plant genera, including crop, ornamental, and wild species (Fulton 1948). Due to its extensive host range and strain adaptations, TSV is found in commercial crops worldwide. Since 1969, however, TSV has not been a problem on soybean or commonly reported until the 2013 season, when it was found in fields throughout Iowa. A similar situation is found throughout the Midwest, with TSV being reported in recent years in Illinois, Kansas, and Wisconsin, as well as Ontario, Canada

Influence of Pleistocene glacial deposits on the transport of agricultural nitrate in the river Wensum catchment, UK

Mitigating NO3− pollution requires an understanding of the hydrological processes controlling contaminant mobilisation and transport, particularly in agricultural catchments underlain by Pleistocene glacial deposits. Focusing on the Wensum catchment in East Anglia, UK, precipitation (n = 20), stream water (n = 50), field drainage (n = 22) and groundwater (n = 84) samples collected between February–March 2011 and April–September 2012 were variously analysed for water stable isotopes (δ2HH2O and δ18OH2O), the dual-isotopes of NO3− (δ15NNO3 and δ18ONO3), groundwater residence time indicators (CFCs and SF6) and hydrochemical parameters. The residence time indicators suggested a component of modern (post-1960) groundwater throughout the sequence of glacial deposits that corresponds with the penetration of agricultural NO3−. Denitrification and lower NO3− concentrations (<8 mg L−1) are observed in the glacial tills, compared with higher NO3− concentrations (<90 mg L−1) observed under more oxidising conditions in the glacial sands and gravels. Storm hydrograph separation for two storms in April and September 2012 using two- and three-component mixing models showed a faster response with field drainage (36–38 %) and baseflow (5–37 %) contributing to the total stream discharge in areas of clay loam soils over glacial tills. In these areas, the dual stable isotopes of NO3− (δ15NNO3 = +11.8 ‰ and δ18ONO3 = +7.1 ‰) indicated a denitrified source of nitrogen from field drainage and groundwater. In comparison, a dampened response and a higher percentage of baseflow (29–80 %) was observed in areas of sandy clay loam soils over glacial sands and gravels. In these areas, mean NO3− isotopic signatures (δ15NNO3 = +7.8 ‰ and δ18ONO3 = +5.0 ‰) indicated a source of nitrified NH4+. In conclusion, understanding hydrological processes in catchments underlain by variable glacial deposits can inform nutrient management plans and cultivation practices to reduce the risk of agricultural NO3− contamination

Randomized Controlled Trial of Mechanical Thrombectomy Versus Catheter-directed Thrombolysis for Acute Hemodynamically Stable Pulmonary Embolism: Rationale and Design of the PEERLESS Study.

BACKGROUND The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the Pulmonary Embolism Response Team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and non-thrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients. METHODS The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a non-randomized MT cohort for separate analysis. The primary endpoint will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary endpoints. Other key secondary endpoints include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit. IMPLICATIONS PEERLESS is the first RCT to compare two different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted