Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.Peer reviewedFinal Published versio

Magnetic properties of Hydrogenated Li and Co doped ZnO nanoparticles

The effect of hydrogenation on magnetic properties of Zn0.85Co0.05Li0.10O nanoparticles is presented. It was found that the sample hydrided at room temperature (RT) showed weak ferromagnetism (FM) while that hydrided at 400oC showed robust ferromagnetism at room temperature. In both cases reheating the sample at 400oC in air converts it back into paramagnetic state (P) completely. The characterization of samples by X-ray and electron diffraction (ED) showed that room temperature ferromagnetism observed in the samples hydrogenated at RT is intrinsic in nature whereas that observed in the samples hydrogenated at 400oC is partly due to the cobalt metal clusters.Comment: 10 pages, 3 figure

Graphene-Enabled Electrodes for Electrocardiogram Monitoring

The unique parameters of Graphene (GN), notably its considerable electron mobility, high surface area and electrical conductivity are bringing extensive attention into the wearable technologies. This work presents a novel Graphene-based electrode for acquisition of electrocardiogram (ECG). The proposed electrode was fabricated by coating GN on top of metallic layer of Ag/AgCl electrode using chemical vapor deposition (CVD) technique. To investigate the performance of the fabricated GN-based electrode, two types of electrodes were fabricated with different sizes to conduct the signal qualities and the skin-electrode contact impedance measurements. Performances of the GN-enabled electrodes were compared to the conventional Ag/AgCl electrodes in terms of ECG signal quality, skin-electrode contact impedance, signal-to-noise ratio (SNR) and response time. Experimental results showed the proposed GN-based electrodes produced better ECG signals, higher SNR (improved by 8%) and lower contact impedance (improved by 78%) values than conventional ECG electrodes

Morphine Analgesia Pre-PPCI Is Associated with Prothrombotic State, Reduced Spontaneous Reperfusion and Greater Infarct Size

Schattauer GmbH Stuttgart.The emergency management of ST-elevation myocardial infarction (STEMI) involves treatment with dual-antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PPCI). Pain is generally treated with opiates, which may delay gastric transit and reduce DAPT absorption. We sought to assess the effect of morphine on reperfusion, infarct size and thrombotic status in 300 patients presenting for PPCI. Morphine was given in a non-randomized fashion as required by emergency teams en route to the heart attack centre. All patients received DAPT and PPCI according to standard care, with optional glycoprotein IIb/IIIa inhibitor (GPI) use. Patients were assessed for ST-segment resolution, coronary flow, thrombotic status and peak troponin. Patients receiving morphine (n = 218; 72.7%) experienced less spontaneous ST-segment resolution pre-PPCI, lower rate of TIMI 2/3 flow in the infarct-related artery pre-PPCI and higher peak troponin level post-PPCI (median [interquartile range]; 1,906 [1,002-4,398] vs. 1,268 [249-2,920] ng/L; p = 0.016) than those who did not. Patients receiving morphine exhibited significantly enhanced platelet reactivity and impaired endogenous fibrinolysis on arrival, compared with no-morphine patients. Morphine administration was an independent predictor of failure of spontaneous ST-segment resolution after adjustment for other variables (odds ratio: 0.26; confidence interval: 0.08-0.84; p = 0.025). Among patients receiving GPI, there was no difference in pre-PPCI flow or peak troponin according to morphine use, suggesting that the adverse effects of morphine relate to delayed DAPT absorption, which may be overcome by GPI. Our hypothesis-generating data suggest that morphine use in STEMI is associated with enhanced platelet reactivity, reduced spontaneous myocardial reperfusion (pre-PPCI) and larger infarct size, and these adverse effects may be influenced by GPI use. CLINICAL TRIAL REGISTRATION:  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02562690.Peer reviewedFinal Accepted Versio

Use of bioresorbable vascular scaffold : a meta-analysis of patients with coronary artery disease

BACKGROUND: Differences in outcomes between bioresorbable vascular scaffold (BVS) systems and drug-eluting metal stents (DES) have not been fully evaluated. We aimed to compare clinical and angiographic outcomes in randomised studies of patients with coronary artery disease (CAD), with a secondary analysis performed among registry studies. METHODS: A meta-analysis comparing outcomes between BVS and DES in patients with CAD. Overall estimates of treatment effect were calculated with random-effects model and fixed-effects model. RESULTS: In 6 randomised trials (3818 patients), BVS increased the risk of subacute stent thrombosis (ST) over and above DES (OR 2.14; CI 1.01 to 4.53; p=0.05), with a trend towards an increase in the risk of myocardial infarction (MI) (125 events in those assigned to BVS and 50 to DES; OR 1.36; CI 0.97 to 1.91; p=0.07). The risk of in-device late lumen loss (LLL) was higher with BVS than DES (mean difference 0.08 mm; CI 0.03 to 0.13; p=0.004). There was no difference in the risk of death or target vessel revascularisation (TVR) between the two devices. In 6 registry studies (1845 patients), there was no difference in the risk of death, MI, TVR or subacute ST between the two stents. Final BVS dilation pressures were higher in registry than in randomised studies (18.7±4.6 vs 15.2±3.3 atm; p<0.001). CONCLUSIONS: Patients treated with BVS had an increased risk of subacute ST and slightly higher LLL compared with those with DES, but this might be related to inadequate implantation techniques, in particular device underexpansion.Peer reviewedFinal Published versio

Impaired endogenous fibrinolysis at high shear using a point-of-care test in STEMI is associated with alterations in clot architecture

© The Author(s) 2019Impaired endogenous fibrinolysis is an adverse prognostic biomarker in acute coronary syndrome (ACS). Abnormally dense in vitro fibrin thrombi have been demonstrated in ACS patients and related to hypofibrinolysis using cumbersome, laboratory-based methods. We aimed to assess endogenous fibrinolysis using a point-of-care technique and relate this to clot architecture. From patients with ST-segment elevation myocardial infarction (STEMI), venous blood was drawn immediately on arrival to assess thrombotic status. Blood was assessed using the point-of-care Global Thrombosis Test which measures occlusive thrombus formation under high shear and subsequently endogenous fibrinolysis (lysis time, LT). Two samples per patient were run in parallel. In one channel, the measurement was allowed to proceed as normal. In the other, after occlusion, thrombus was extracted, washed, fixed in glutaraldehyde, dried, sputter-coated, and assessed using scanning electron microscope. Endogenous fibrinolysis was strongly associated fibrin fibre thickness (p = 0.0001). As LT increased (less efficient fibrinolysis), the fibrin network of the thrombus was significantly more compact and dense, with thinner fibrin fibres and smaller gaps. Fibrin fibre thickness correlated inversely with LT (r = - 0.89, p = 0.001). Adverse clot architecture in vitro is directly related to impaired endogenous fibrinolysis using a relatively new point-of-care technique in patients with STEMI. This may transform the relevance of fibrin clot architecture from an off-line laboratory association to being directly relevant to endogenous fibrinolysis at the patient bedside, which could be used as a near-patient test to guide prognosis and assess the effect of treatment.Peer reviewedFinal Published versio

Relative effects of different non-vitamin K antagonist oral anticoagulants on global thrombotic status in atrial fibrillation

This is an Accepted Manuscript of an article published by Taylor & Francis GroupNon-vitamin K antagonist oral anticoagulants (NOACs) reduce the risk of thromboembolism in patients with atrial fibrillation (AF). There has been no head-to-head comparison of the effect of these agents on ex vivo thrombotic and thrombolytic status. Enhanced platelet reactivity and impaired endogenous thrombolysis are risk factors for recurrent thrombotic events. We aimed to assess the comparative effect of NOACs and warfarin using an ex vivo test of thrombosis and thrombolysis. Eighty patients with newly diagnosed non-valvular AF were tested before, and after being established on apixaban (n = 20), dabigatran (n = 20), rivaroxaban (n = 20), or warfarin (n = 20). Thrombotic status was assessed with the automated, point-of-care Global Thrombosis Test (GTT) that assesses both platelet reactivity and endogenous thrombolysis from native blood. The time taken to form an occlusive thrombus (occlusion time, OT) and the time required to restore flow through endogenous thrombolysis (lysis time, LT) were measured. All anticoagulants caused OT prolongation compared to baseline (apixaban 403 ± 102s vs. 496 ± 125s, p = 0.006; dabigatran 471 ± 106s vs. 656 ± 165s, p < 0.00001; rivaroxaban 381 ± 119s vs. 579 ± 158, p < 0.00001; warfarin 420 ± 145s vs. 604 ± 124s, p < 0.00001). Apixaban reduced LT from baseline (1895[1702-2167]s vs. 1435[347-1990]s; p = 0.006). A trend for LT reduction was seen with other NOACs (dabigatran 1594[1226-2069]s vs. 1539[561-2316]s, p = 0.499; rivaroxaban 2085[1366-2428]s vs. 1885[724-2420]s, p = 0.295) but not with warfarin (1490[1206-1960]s vs. 1776[1545-2334], p = 0.601). Our results suggest that NOACs and warfarin have a similar favorable effect on reducing platelet reactivity. All NOACs exhibited a trend toward enhancing endogenous thrombolytic status, although this was significant only for apixaban. This raises the possibility of using NOACs to enhance impaired endogenous fibrinolysis in patients at high-thrombotic risk.Peer reviewedFinal Accepted Versio

An Experimental Study on Solar Flat Plate Collector Using an Alternative Working Fluid

This paper describes the performance of a solar water heater with an alternative working fluid. A solar flat plate collector of fIxed orientation was fabricated and connected to a heat exchanger, which was kept inside the water storage drum. The developed collector was a low temperature device operating with the temperature range of ambient to 100°C. Acetone was selected as an alternative working fluid and allowed to re-eirculate in a closed loop. A shell and tube type heat exchanger (non-mixing) was designed and fabricated for the heat transfer between acetone and water. The solar intensity increased from 55 mw/cm2 at 8.30 am to 85 mw/cm2 at 1.30 pm and decreased to 64 mw/cm2 at 5.00 pm. The absorber plate temperature, which remained nearly constant for the first two hours, went up to 90°C in the next two hours. It was nearly constant from 11.00 am to 1.30 pm and then dropped down to 72°C in the afternoon. The hot fluid was found to loose heat to the surrounding water at more or less constant rate from 11.30 am to 5.00 pm. The highest temperature of acetone (70°C) was observed during 1.00 pm to 2.00 pm. The temperature of water increased from 30°C to a maximum of 62°C. Overall efficiency of the system was found to be 45% while considering the solar input to the heat gained by the water. Alternative working fluids such as acetone, methanol or ethanol may be considered for substituting water in the flat plate collector in view of the fact that the fluids have low boiling point coupled with high latent heat of evaporation

Improved control strategy of DFIG-based wind turbines using direct torque and direct power control techniques

This paper presents different control strategies for a variable-speed wind energy conversion system (WECS), based on a doubly fed induction generator. Direct Torque Control (DTC) with Space-Vector Modulation is used on the rotor side converter. This control method is known to reduce the fluctuations of the torque and flux at low speeds in contrast to the classical DTC, where the frequency of switching is uncontrollable. The reference for torque is obtained from the maximum power point tracking technique of the wind turbine. For the grid-side converter, a fuzzy direct power control is proposed for the control of the instantaneous active and reactive power. Simulation results of the WECS are presented to compare the performance of the proposed and classical control approaches.Peer reviewedFinal Accepted Versio

Biodegradation of lignocellulosic residues of water hyacinth (Eichhornia crassipes) and response surface methodological approach to optimize bioethanol production using fermenting yeast Pachysolen tannophilus NRRL Y-2460

The objective of this research was to investigate biodegradation of water hyacinth (Eichhornia crassipes) to produce bioethanol using dilute-acid pretreatment (1 % sulfuric acid) results in high hemicellulose decomposition and using yeast (Pachysolen tannophilus) as bioethanol producing strain. A maximum ethanol yield of 1.14 g/L with coefficient, 0.24 g g-1; productivity, 0.015 g l-1h-1 was comparable to predicted value 32.05 g/L obtained by Central Composite Design (CCD). Maximum ethanol yield coefficient was comparable to those obtained through enzymatic saccharification and fermentation of acid hydrolysate using fully equipped fermentor. Although maximum ethanol concentration was low in lab scale, the improvement of lignocellulosic ethanol yield is necessary for large scale production