A comprehensive model was developed to simulate gasification of pine sawdust in the presence of both air and steam. The proposed model improved upon the premise of an existing ASPEN PLUS-based ...biomass gasification model. These enhancements include the addition of a temperature-dependent pyrolysis model, an updated hydrodynamic model, more extensive gasification kinetics and the inclusion of tar formation and reaction kinetics. ASPEN PLUS was similarly used to simulate this process; however, a more extensive FORTRAN subroutine was applied to appropriately model the complexities of a Bubbling Fluidized Bed (“BFB”) gasifier. To confirm validity, the accuracy of the model's predictions was compared with actual experimental results. In addition, the relative accuracy of the comprehensive model was compared to the original base-model to see if any improvement had been made.
Results show that the model predicts H2, CO, CO2, and CH4 composition with reasonable accuracy in varying temperature, steam-to-biomass, and equivalence ratio conditions. Mean error between predicted and experimental results is calculated to range from 6.1% to 37.6%. Highest relative accuracy was obtained in CO composition prediction while the results with the least accuracy were for CH4 and CO2 estimation at changing steam-to-biomass ratios and equivalence ratios. When compared to the original model, the comprehensive model predictions of H2 and CO molar fractions are more accurate than those of CO2 and CH4. For CO2 and CH4, the original model predicted with comparable or better accuracy when varying steam-to-biomass ratio and equivalence ratios but the comprehensive model performed better at varying temperatures.
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•A comprehensive kinetic model was developed to include pyrolysis and tar reactions.•The highest accuracy was obtained in CO and H2 compositions predicted by the model.•Reaction temperature had the greatest overall influence on H2 production.•Mass transfer limitations showed a non-negligible effect on the CO/CO2 ratio.•CH4 is highly dependent on biomass decomposition in pyrolysis before gasification.
Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a ...widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease.
Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo.
54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p < 0.05, 90% power). Primary outcomes are cerebral blood flow in subcortical white matter and deep grey nuclei. Secondary outcomes are cortical grey matter cerebral blood flow and performance on cognitive tests (reaction time, information processing speed, digit span forwards and backwards, semantic fluency).
Recruitment started on 4th September 2015 and 36 participants have completed to date (19th April 2017). No serious adverse events have occurred. All participants have been recruited from one centre, St George's University Hospitals NHS Foundation Trust.
European Union Clinical Trials Register: EudraCT number 2015-001235-20 . Registered on 13 May 2015.
From 2016 to 2021, the National Institutes of Health Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke initiated ten multicenter ...randomized controlled clinical trials. Optimal subject randomization designs are demanded with 4 critical properties: (1) protection of treatment assignment randomness, (2) achievement of the desired treatment allocation ratio, (3) balancing of baseline covariates, and (4) ease of implementation. For acute stroke trials, it is necessary to minimize the time between eligibility assessment and treatment initiation. This article reviews the randomization designs for 3 trials currently enrolling in Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke, the SATURN (Statins in Intracerebral Hemorrhage Trial), the MOST (Multiarm Optimization of Stroke Thrombolysis Trial), and the FASTEST (Recombinant Factor VIIa for Hemorrhagic Stroke Trial). Randomization methods utilized in these trials include minimal sufficient balance, block urn design, big stick design, and step-forward randomization. Their advantages and limitations are reviewed and compared with traditional stratified permuted block design and minimization.
•More drugs are needed for vascular causes of dementia.•Single-administration tadalafil did not enhance cognition in people with small vessel disease.•Chronic tadalafil treatment may have cognitive ...effects.
Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52–87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27, range 15–30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies.
http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015–001,235–20NCT00123456.
Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) ...is reduced in SVD, particularly within white matter.
Here we quantified test–retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days).
Test–retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient 95%CI: 0.758 0.616, 0.852 for whole brain, 0.842 0.743, 0.905 for total grey matter, 0.771 0.636, 0.861 for deep grey matter (caudate-putamen and thalamus), 0.872 0.790, 0.923 for normal-appearing white matter (NAWM) and 0.780 0.650, 0.866 for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM).
We conclude that pCASL has high test–retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.
All data come from the PASTIS trial, prospectively registered at:
https://eudract.ema.europa.eu
(2015-001235-20, registered 13/05/2015),
http://www.clinicaltrials.gov
(NCT02450253, registered 21/05/2015).
Involved in the coagulation cascade, factor Xa (FXa) is a serine protease which has received great interest as a potential target for the development of new antithrombotics. Although there is a great ...wealth of structural data on thrombin complexes, few structures of ligand/FXa complexes have been reported, presumably because of the difficulty in growing crystals. Reproducible crystallization conditions for human des-Gla1-45 coagulation FXa have been found. This has led to an improvement in the diffraction quality of the crystals (about 2.1 A) when compared to the previously reported forms (2.3-2.8 A) thus providing a suitable platform for a structure-based drug design approach. A series of crystal structures of noncovalent inhibitors complexed with FXa have been determined, three of which are presented herein. These include compounds containing the benzamidine moiety and surrogates of the basic group. The benzamidine-containing compound binds in a canonical fashion typical of synthetic serine protease inhibitors. On the contrary, molecules that contain surrogates of the benzamidine group do not make direct hydrogen-bonding interactions with the carboxylate of Asp189 at the bottom of the S1 pocket. The structural data provide a likely explanation for the specificity of these inhibitors and a great aid in the design of bioavailable potent FXa inhibitors.
Over the last few decades, research on the abatement of carbon dioxide (CO2) gas has gained momentum, due to its increasing atmospheric levels. This study investigated high‐temperature steam‐only ...gasification of woody biomass for the production of high‐purity hydrogen integrated with CO2 capture in a moving‐bed gasifier. Extensive process modelling and simulation were performed using the superior solid handling features of the Aspen Plus process simulator software. After validating the model with experimental data from a demonstration plant available in the open literature, a reversible carbonation‐calcination reaction of calcium oxide (CaO) with CO2 was added to the system. Sensitivity analyses were conducted to verify the predictive accuracy of the model. The effects of steam‐to‐carbon (S/C) ratio on the resulting gas composition were thoroughly studied to delineate the complex process of gasification. Beyond the mitigation of CO2 emissions, the introduction of a CaO‐based sorbent in the process simulation significantly enhanced hydrogen production by simultaneously promoting the forward water‐gas shift reaction and reducing tars through increased tar‐cracking reactions. The results show that hydrogen of a higher purity was produced with the inclusion of dry‐sorption CO2 capture in the gasification process. Moreover, the addition of the sorbent increased the higher heating values (HHV) by 3 times and improved the cold gas efficiency by 34 %.
Results of a fully three‐dimensional model of the interaction of the solar wind with the local interstellar medium are presented. The effects of charge‐exchange with interstellar neutral hydrogen are ...taken into account self‐consistently, while the effects of hot solar wind neutral hydrogen, as well as cosmic rays and magnetic fields, are ignored in this study. In accord with solar medium observations by Ulysses, the solar wind is assumed to depend on heliolatitude. Two large, long‐lived polar coronal holes, one in the northern hemisphere and the other in the southern hemisphere, are assumed to produce a hot, low‐density, high‐speed wind which bounds a cooler, higher‐density, low‐speed ecliptic wind. The solar wind boundary conditions, which allow for a 1.5 increase in solar wind ram pressure over the poles of the Sun compared with the ecliptic plane, are drawn from published Ulysses data Phillips et al., 1995, 1996. The results of this simulation are compared with the no‐charge‐exchange asymmetric solar wind simulation, described by Pauls and Zank 1996. It is found that the elongation of the heliosphere along the solar poles, resulting from the ram pressure increase with heliolatitude, induces a greater influx of interstellar hydrogen over the poles of the Sun than in the ecliptic plane. This, in turn, reduces the extent of elongation of the heliosphere along the poles of the Sun. The vorticity, found in the no‐charge‐exchange simulation, is absent in the presence of charge‐exchange. Once again, as found by Baranov and Malama 1993 and Pauls et al. 1995, the interaction of the solar wind with the local interstellar medium is influenced strongly by charge‐exchange processes.
Introduction
There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases ...cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI.
Methods
In a double‐blind, placebo‐controlled, cross‐over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling.
Results
Tadalafil increased CBF non‐significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P < .001). No serious adverse events were observed.
Discussion
This trial did not identify a significant treatment effect of single‐administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.
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