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Mechanistic Insights Into the Therapeutic Use of High-Dose Allopurinol in Angina Pectoris
No full textObjectives The aim of this study was to evaluate the effect of high-dose allopurinol on vascular oxidative stress (OS) and endothelial function in subjects with stable coronary artery disease (CAD).Background Allopurinol, a xanthine oxidase inhibitor, prolongs the time to chest pain during exercise in angina. We sought to ascertain whether allopurinol also improves endothelial dysfunction in optimally treated CAD patients, because such an effect might be of value to reduce future cardiovascular mortality. The mechanism of the anti-ischemic effect of allopurinol could be related to its reducing xanthine oxidase-induced OS, and our second aim was to see whether allopurinol really does reduce vascular tissue OS in CAD patients.Methods A randomized, double-blind, placebo-controlled, crossover study was conducted in 80 patients with CAD, comparing allopurinol (600 mg/day) with placebo. Endothelial function was assessed by forearm venous occlusion plethysmography, flow-mediated dilation, and pulse wave analysis. Vascular OS was assessed by intra-arterial co-infusion of vitamin C and acetylcholine.Results Compared with placebo, allopurinol significantly improved endothelium-dependent vasodilation, by both forearm venous occlusion plethysmography (93 +/- 67% vs. 145 +/- 106%, p = 0.006) and flow-mediated dilation (4.2 +/- 1.8% vs. 5.4 +/- 1.7%, p < 0.001). Vascular oxidative stress was completely abolished by allopurinol. Central augmentation index improved significantly with allopurinol (2.6 +/- 7.0%, p < 0.001) but not with placebo.Conclusions Our study demonstrates that, in optimally treated CAD patients, high-dose allopurinol profoundly reduces vascular tissue OS and improves 3 different measures of vascular/endothelial dysfunction. The former effect on OS might underpin the anti-ischemic effect of allopurinol in CAD. Both effects (on OS and endothelial dysfunction) increase the likelihood that high-dose allopurinol might reduce future cardiovascular mortality in CAD, over and above existing optimum therapy. (Exploring the therapeutic potential of xanthine oxidase inhibitor allopurinol in angina; ISRCTN15253766) (J Am Coll Cardiol 2011;58:820-8) (C) 2011 by the American College of Cardiology Foundation</p
Peer tutoring in reading:the effects of role and organization on two dimensions of self-esteem
No full textBackground. Paired reading (PR) is an application of peer tutoring. It has been extensively researched, and its efficacy across a range of outcomes has been established. Benefits include improvements in key reading skills, and also in affective aspects of learning. Several studies have shown gains in self-esteem, although measurement methods have varied, and the model of self-esteem has rarely been clearly articulated.Aims. To investigate the changes in self-esteem of children participating in a randomized trial of PR over a 15-week treatment period. To investigate the relative contribution of self-worth and self-competence to any gains in self-esteem. To investigate whether the pattern of change differs in children who take on different roles in the PR process.Participants. The participants comprised a subset of a large-scale randomized trial of peer learning (The Fife Peer Learning Project). Four schools were randomly selected from schools allocated to the same-age PR condition, and four schools from those allocated to the cross-age PR condition. The same-age group consisted of 87 primary 6 children (10-11 years old). The cross-age group consisted of 81 primary 6 children. The controls, from schools randomly selected from a neighbouring authority, consisted of 92 primary 6 children.Method. A pre-post design employing self-report measures of self-esteem. Rosenberg's Self-Esteem Scale was used, with scores analysed for worth and competence. The treatment period was 15 weeks, with the participants following a prescribed PR process.Results. Significant pre-post gains were noted in self-esteem, driven predominantly by improved beliefs about competence, in both same-age and cross-age conditions, but not for controls. Gains were also seen in self-worth in the cross-age condition. Further analyses of the influence of organizational condition (same-age or cross-age) and role played (tutor vs. tutee) showed significant differences between same-age tutors and cross-age tutors in relation to self-worth. Effect sizes were generally small or moderate.Conclusions. The findings provide further support for the belief that PR can enhance self-esteem. Importantly, the use of a two-dimensional model provides extra information about self-perceptions in PR contexts: first, the central role of self-competence; and second, the gains in self-worth which are associated with tutoring younger children (but not same-age peers). This new information has educational significance for schools considering the potential of peer tutoring and the benefits of different organizational conditions.</p
Centrifuge modelling of hillslope debris flow initiation
No full textPhysical modelling of hillslope debris flow initiation was undertaken using the geotechnical beam centrifuge at the University of Dundee. The tests were carried out on model slopes consisting of soils with known properties prepared with constant initial density and material thickness. The results showed that soils with a higher silt fraction can sustain a higher increase in pore water pressure and thus a greater reduction in effective stress before failure is induced. This suggests that sand rich soils with lower fines content are geotechnically more susceptible to slope failure and that observed higher spatial frequencies of debris flow on slopes with coarse grained bedrocks can be partially explained in terms of lower critical pore pressure failure thresholds amongst the sandier soil matrixes produced from such lithologies. Differences in rates of water ingress into the model soils required to trigger a critical rise in pore pressures during the tests provide insights into the varying synoptic conditions and antecedent rainfall characteristics that are likely to trigger debris flows in different soil types
Role of symptoms and lung function in determining asthma control in smokers with asthma
No full textCigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known
The Flash community:implications for post-conceptualism
No full textComplementing a broader international research paradigm shift, Electronic Literature scholars and practitioners alike have expressed a desire to expand the field to include deep collaborations with other disciplines. In achieving such a goal any original indigenous ideologies and aesthetics may be challenged. This dialectical tension between striving to be niche/identifiable/original in a mixed discipline economy faced with contemporary descriptors of ‘human experience’ such as Baumanr’s Liquid Modernity (2000), Antonelli’s Elasticity (2008) or even Turkle’s "life mix" (2011) remains key to facing this challenge.Using new interviews, emergent theories and archival resources this paper argues that the Flash community has already faced the issue of contemporary homogeneity driven by our on-going context of rapid technological change, and can be regarded as an exemplar of post-conceptual experimentalism. After a comparative analysis between the Flash Community and Electronic Literature the paper goes on to explore other new insights and considers the implications of being post-conceptual as a future opportunity and/or risk for Electronic Literature
Electrode Configurations for Resistivity Measurements on Concrete
No full textIn this study, two- and four-electrode arrangements were used to evaluate the electrical resistance (hence resistivity) of saturated concrete specimens using both embedded rod-electrodes, external plate-electrodes, and combinations thereof Measurements were obtained mainly at a fixed frequency of 1 kHz. It is shown that the two-electrode external plate measurement system gave higher resistivity values than the four-electrode system; however studying the electrical response in terms of complex impedance, over the frequency range 1 to 10 MHz, revealed that the sponge-contacting system used in the two-electrode method introduced a spurious resistance attributed to the sponge-sample interface.</p
Optimal feature selection for estimating biomass using a genetic algorithm
No full textWhilst the use of SAR and multispectral image texture has shown promise for estimating tropical forest biomass, there remains uncertainty over the optimum number and type of texture features that provide reliable models to estimate biomass across different forest sites. Previous studies have consistently suggested that selecting an appropriate window size for extracting texture is critical, as small window sizes often exaggerate texture whilst larger window sizes create smoothing effects. There are also a variety of image texture features that have previously been correlated with biomass (e.g. wavelet decomposition and GLCM outputs such as entropy, homogeneity, energy etc.). Neural network regression methods allow any number of these variables (and window sizes) to be included in the regression model. However, this increases the dimensionality of the input data with resultant effects on the ability of the network to learn and generalise. It is desirable to try and restrict the dimensionality of the inputs, particularly when using small samples for predictive modelling, a characteristic of many biomass estimation studies. Common methods for feature selection include Principal Components Analysis (PCA) but are not always suited to this kind of problem. Here, we compare PCA feature selection with a Genetic Algorithm (GA) approach, using separately an artificial neural network and Fuzzy c-means as fitness functions. A combination of texture features were derived from SAR and multispectral images of three tropical forest sites. Evaluation of the optimum combination of these features to estimate aboveground biomass was conducted by applying each of the three feature selection methods in turn, and then using the features selected as inputs to estimate biomass with a neural network. The correlation between the input training data and the unseen testing data was used as a measure of model performance for estimating biomass. The results indicated that features selected using the GA approach with a neural network used as a fitness function produced the strongest relationships with biomass at the three sites (r=0.91, 0.89 and 0.87 for Brazil (n=9), Malaysia (n=9) and Thailand (n=13) respectively), compared to the other GA approach and PCA. In all cases, the texture features and window sizes selected varied, although some commonality in selection between Malaysia and Brazil sites was noted. Overall, the GA approaches selected features that produced stronger relationships than PCA with evidence that these hold much promise for determining the optimum set of inputs for biomass estimation models, although much work is still required. <br/
The role of the funnel plot in detecting publication and related biases in meta-analysis
No full textA randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell's palsy:the BELLS study
No full textTo determine whether oral prednisolone or aciclovir, used separately or in combination, early in the course of Bell's palsy, improves the chances of recovery at 3 and 9 months
Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors
No full textTrypanothione synthetase (TryS) is essential for the survival of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis. It is one of only a handful of chemically validated targets for T. brucei in vivo. To identify novel inhibitors of TbTryS we screened our in-house diverse compound library that contains 62?000 compounds. This resulted in the identification of six novel hit series of TbTryS inhibitors. Herein we describe the SAR exploration of these hit series, which gave rise to one common series with potency against the enzyme target. Cellular studies on these inhibitors confirmed on-target activity, and the compounds have proven to be very useful tools for further study of the trypanothione pathway in kinetoplastids.</p
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