S-Nitrosoglutathione reduces asymptomatic embolization after carotid angioplasty

Background: The major complication of carotid angioplasty is embolic stroke, which may occur after balloon inflation and deflation or in the early postintervention period. Platelet adhesion and aggregation to the angioplasty site with subsequent embolization seems to plays a major role in early postangioplasty embolization and stroke. During this period, asymptomatic embolic signals can be detected in patients by transcranial Doppler ultrasound despite aspirin and heparin treatment. S-Nitrosoglutathione (GSNO) is a nitric oxide donor that appears to have relative platelet specificity. We evaluated its effectiveness in reducing embolization after carotid angioplasty. Methods and results: Sixteen patients undergoing carotid angioplasty and stenting for symptomatic 70% internal carotid artery stenosis were randomized in a double-blind manner to GSNO or placebo given after surgery for 90 minutes. All patients were pretreated with aspirin and given heparin for 24 hours after the procedure. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 1 hour before treatment and at 0 to 3, 6, and 24 hours after treatment. GSNO resulted in a rapid reduction in the frequency of embolic signals of 95% at 0 to 3 hours and 100% at 6 hours (P=0.007 and P=0.01 versus placebo, respectively). In the placebo group, 2 patients experienced ipsilateral stroke after the angioplasty. No cerebrovascular events occurred in the GSNO group. Conclusions: S-Nitrosoglutathione was highly effective in rapidly reducing the frequency of embolic signals after endovascular treatment for symptomatic high-grade carotid stenosis

The use of embolic signal detection in multicenter trials to evaluate antiplatelet efficacy: signal analysis and quality control mechanisms in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial

<p><b>Background and Purpose:</b> The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts.</p> <p><b>Methods:</b> As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (ps±values). For all DATs included in CARESS (n=300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator).</p> <p><b>Results:</b> For the reference tape, the cumulative ps±value was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was ps+=0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative ρ=0.84; P<0.001).</p> <p><b>Conclusion:</b> Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.</p&gt

EFEKTIVITAS Trichlorton 95 SP. SEBAGAI PEMBASMI HAMA JEMBRET (Mesopodopsis sp.) PADA BUDI DAYA UDANG WINDU

Trichtoffon 95 SP adalah bahan aktif dari Dyvon yang digunakan untuk membasmi hama jembret pada budi daya udang windu di tambak. Percobaan menggunakan bak fiber sebanyak 21 buah yang diisi dengan air laut 50 L/bak. Tujuan penelitian ini untuk mendapatkan konsentrasi yang tepat yang dapat mematikan hama jembret, namun aman terhadap udang windu

The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1–6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7–34 pathogenic variant

Purpose: CADASIL is a small-vessel disease caused by a cysteine-altering pathogenic variant in one of the 34 epidermal growth factor-like repeat (EGFr) domains of the NOTCH3 protein. We recently found that pathogenic variant in EGFr domains 7\u201334 have an unexpectedly high frequency in the general population (1:300). We hypothesized that EGFr 7\u201334 pathogenic variant more frequently cause a much milder phenotype, thereby explaining an important part of CADASIL disease variability. Methods: Age at first stroke, survival and white matter hyperintensity volume were compared between 664 CADASIL patients with either a NOTCH3 EGFr 1\u20136 pathogenic variant or an EGFr 7\u201334 pathogenic variant. The frequencies of NOTCH3 EGFr 1\u20136 and EGFr 7\u201334 pathogenic variant were compared between individuals in the genome Aggregation Database and CADASIL patients. Results: CADASIL patients with an EGFr 1\u20136 pathogenic variant have a 12-year earlier onset of stroke than those with an EGFr 7\u201334 pathogenic variant, lower survival, and higher white matter hyperintensity volumes. Among diagnosed CADASIL patients, 70% have an EGFr 1\u20136 pathogenic variant, whereas EGFr 7\u201334 pathogenic variant strongly predominate in the population. Conclusion: NOTCH3 pathogenic variant position is the most important determinant of CADASIL disease severity, with EGFr 7\u201334 pathogenic variant predisposing to a later onset of stroke and longer survival

Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388)

RATIONALE: The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. HYPOTHESIS: Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective. SAMPLE SIZE ESTIMATES: The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. METHODS AND DESIGN: Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation. STUDY OUTCOME: The primary outcome is stroke recurrence and its severity ('ordinal recurrence' based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events). DISCUSSION: The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack

Universality in the Screening Cloud of Dislocations Surrounding a Disclination

A detailed analytical and numerical analysis for the dislocation cloud surrounding a disclination is presented. The analytical results show that the combined system behaves as a single disclination with an effective fractional charge which can be computed from the properties of the grain boundaries forming the dislocation cloud. Expressions are also given when the crystal is subjected to an external two-dimensional pressure. The analytical results are generalized to a scaling form for the energy which up to core energies is given by the Young modulus of the crystal times a universal function. The accuracy of the universality hypothesis is numerically checked to high accuracy. The numerical approach, based on a generalization from previous work by S. Seung and D.R. Nelson ({\em Phys. Rev A 38:1005 (1988)}), is interesting on its own and allows to compute the energy for an {\em arbitrary} distribution of defects, on an {\em arbitrary geometry} with an arbitrary elastic {\em energy} with very minor additional computational effort. Some implications for recent experimental, computational and theoretical work are also discussed.Comment: 35 pages, 21 eps file

Energy-Dependent Timing of Thermal Emission in Solar Flares

We report solar flare plasma to be multi-thermal in nature based on the theoretical model and study of the energy-dependent timing of thermal emission in ten M-class flares. We employ high-resolution X-ray spectra observed by the Si detector of the "Solar X-ray Spectrometer" (SOXS). The SOXS onboard the Indian GSAT-2 spacecraft was launched by the GSLV-D2 rocket on 8 May 2003. Firstly we model the spectral evolution of the X-ray line and continuum emission flux F(\epsilon) from the flare by integrating a series of isothermal plasma flux. We find that multi-temperature integrated flux F(\epsilon) is a power-law function of \epsilon with a spectral index (\gamma) \approx -4.65. Next, based on spectral-temporal evolution of the flares we find that the emission in the energy range E= 4 - 15 keV is dominated by temperatures of T= 12 - 50 MK, while the multi-thermal power-law DEM index (\gamma) varies in the range of -4.4 and -5.7. The temporal evolution of the X-ray flux F(\epsilon,t) assuming a multi-temperature plasma governed by thermal conduction cooling reveals that the temperature-dependent cooling time varies between 296 and 4640 s and the electron density (n_e) varies in the range of n_e= (1.77-29.3)*10^10 cm-3. Employing temporal evolution technique in the current study as an alternative method for separating thermal from non-thermal components in the energy spectra, we measure the break-energy point ranging between 14 and 21\pm1.0 keV.Comment: Solar Physics, in pres

Screening and techno-economic assessment of biomass-based power generation with CCS technologies to meet 2050 CO2 targets

Biomass-based power generation combined with CO2 capture and storage (Biopower CCS) currently represents one of the few practical and economic means of removing large quantities of CO2 from the atmosphere, and the only approach that involves the generation of electricity at the same time. We present the results of the Techno-Economic Study of Biomass to Power with CO2 capture (TESBiC) project, that entailed desk-based review and analysis, process engineering, optimisation as well as primary data collection from some of the leading pilot demonstration plants. From the perspective of being able to deploy Biopower CCS by 2050, twenty-eight Biopower CCS technology combinations involving combustion or gasification of biomass (either dedicated or co-fired with coal) together with pre-, oxy- or post-combustion CO2 capture were identified and assessed. In addition to the capital and operating costs, techno-economic characteristics such as electrical efficiencies (LHV% basis), Levelised Cost of Electricity (LCOE), costs of CO2 captured and CO2 avoided were modelled over time assuming technology improvements from today to 2050. Many of the Biopower CCS technologies gave relatively similar techno-economic results when analysed at the same scale, with the plant scale (MWe) observed to be the principal driver of CAPEX (£/MWe) and the cofiring % (i.e. the weighted feedstock cost) a key driver of LCOE. The data collected during the TESBiC project also highlighted the lack of financial incentives for generation of electricity with negative CO2 emissions

Baseline characteristics of the 3096 patients recruited into the 'Triple Antiplatelets for Reducing Dependency after Ischemic Stroke' trial.

Background The risk of recurrence following ischemic stroke or transient ischemic attack is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design The triple antiplatelets for reducing dependency after ischemic stroke trial was an international multicenter prospective randomized open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared with guideline treatment in acute ischemic stroke or transient ischemic attack. The primary outcome was stroke recurrence and its severity, measured using the modified Rankin Scale at 90 days. Secondary outcomes included recurrent vascular events, functional measures (cognition, disability, mood, quality of life), and safety (bleeding, death, serious adverse events). Data are number (%) or mean (standard deviation, SD). Results Recruitment ran from April 2009 to March 2016; 3096 patients were recruited from 106 sites in four countries (Denmark 1.6%, Georgia 2.7%, New Zealand 0.2%, UK 95.4%). Randomization characteristics included: age 69.0 (10.1) years; male 1945 (62.8%); time onset to randomization 29.4 (11.9) h; stroke severity (National Institutes for Health Stroke Scale) 2.8 (3.6); blood pressure 143.5 (18.2)/79.5 (11.4) mmHg; IS 2143 (69.2%), transient ischemic attack 953 (30.8%). Conclusion Triple antiplatelets for reducing dependency after ischemic stroke was a large trial of intensive/triple antiplatelet therapy in acute ischemic stroke and transient ischemic attack, and included participants from four predominantly Caucasian countries who were representative of patients in many western stroke services

Correction to: The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1–6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7–34 pathogenic variant

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