The role of urate and xanthine oxidase in vascular oxidative stress:Future directions

Vascular oxidative stress has been shown to be a potent factor in the pathophysiology of endothelial dysfunction. Despite current optimal evidence-based therapy, mortality from various cardiovascular disorders remains high. The search for newer, novel ways of attenuating endothelial dysfunction has yielded several new and exciting possibilities, one of which is the manipulation of urate levels using xanthine oxidase inhibitors. Agents such as allopurinol have shown marked improvements in vascular endothelial function in various cohorts at risk of cardiovascular events. Most of the evidence so far comes from smaller mechanistic studies. The few large randomized controlled trials have failed to show any significant mortality benefit using these agents. This article highlights the potential avenues of further research such as dose-response, and the potential for these agents to regress left ventricular hypertrophy. The role of newer agents such as febuxostat and oxypurinol are discussed as well as potential reasons why some of the current newer agents have failed to live up to the promising early-phase data. It is crucial that these remaining questions surrounding urate, xanthine oxidase and the role of various agents that affect this important oxidative stress-generating system are answered, and therefore these promising agents should not be discarded prematurely

Graduate attributes in the disciplines of Medicine, Dentistry and Veterinary Medicine: a survey of expert opinions

This project was funded by QAA (Scotland).Abstract BACKGROUND: This study was completed as part of a project for the Quality Assurance Agency on the enhancement theme of 'Research teaching linkages: enhancing graduate attributes' in the disciplines of Medicine, Dentistry and Veterinary Medicine. The aims of this investigation were to elucidate a list of desirable research related graduate attributes for the disciplines of Medicine, Dentistry and Veterinary Medicine and provide evidence as to how they could be covered within such curricula. METHODS: Semi structured interviews, symposium breakout sessions and conference workshops were used to define and rank attributes suggested by curricula design experts from the three disciplines. Students graduating from a BSc Medical Science degree program were surveyed to determine how well they felt the curriculum and associated final year project equipped them with the identified attributes. RESULTS: A list of seven high level attributes which were desirable in graduates wishing to pursue either a professional or research career were identified. 105 students reported that a final year project was particularly effective at developing an understanding of the need to have an inquiring mind and critical appraisal skills whilst other components of their degree course covered team working skills, core knowledge and an understanding of ethics and governance. CONCLUSION: This study identified desirable attributes from graduates from medical, dental and veterinary degree programs and provides evidence to support the case for student projects helping to achieve both clinical and research related graduate attributes in medical undergraduates. The project also provides a focus for debate amongst those involved in curriculum design as to whether the attributes identified are those desirable in their graduates and to examine their current curriculum to determine coverage.Peer reviewe

Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress

Oxidative stress plays an important role in the progression of vascular endothelial dysfunction. The two major systems generating vascular oxidative stress are the NADPH oxidase and the xanthine oxidase pathways. Allopurinol, a xanthine oxidase inhibitor, has been in clinical use for over 40 years in the treatment of chronic gout. Allopurinol has also been shown to improve endothelial dysfunction, reduce oxidative stress burden and improve myocardial efficiency by reducing oxygen consumption in smaller mechanistic studies involving various cohorts at risk of cardiovascular events. This article aims to explain the role of xanthine oxidase in vascular oxidative stress and to explore the mechanisms by which allopurinol is thought to improve vascular and myocardial indices

The ERM, Sterling depreciation and Scottish industry

This is the second in a series of papers on the impact of the ERM and of Sterling's recent depreciation on Scottish companies. The first paper (Struthers, 1992) appeared just after Sterling's exit from the ERM in September 1992. That paper analysed perceived costs and benefits of ERM membership on the part of Scottish registered companies. This study is a follow-up to the previous one and is based on another questionnaire survey, this time of the Top 500 Scottish Companies, again as defined by the recently updated Scottish Business Insider database

Recursive integral method for transmission eigenvalues

Recently, a new eigenvalue problem, called the transmission eigenvalue problem, has attracted many researchers. The problem arose in inverse scattering theory for inhomogeneous media and has important applications in a variety of inverse problems for target identification and nondestructive testing. The problem is numerically challenging because it is non-selfadjoint and nonlinear. In this paper, we propose a recursive integral method for computing transmission eigenvalues from a finite element discretization of the continuous problem. The method, which overcomes some difficulties of existing methods, is based on eigenprojectors of compact operators. It is self-correcting, can separate nearby eigenvalues, and does not require an initial approximation based on some a priori spectral information. These features make the method well suited for the transmission eigenvalue problem whose spectrum is complicated. Numerical examples show that the method is effective and robust.Comment: 18 pages, 8 figure

Using the Internet for Organizational Research: A Study of Cynicism in the Workplace

The Internet can be a valuable data collection tool for organizational psychology researchers. It can be less expensive than traditional paper-and-pencil survey methods, and the potential pool of participants is much larger. In addition, it can be used in situations where traditional data collection methods are not feasible, such as research involving sensitive issues such as negative employee attitudes or deviant behaviors at work. In this study, we examined the organizational attitudes of employees from various companies using (a) a snowball sample, who completed a traditional paper and pencil survey (n = 135), and (b) a sample recruited over the Internet, who completed an on-line survey (n = 220). Participants in both the non- Internet and the Internet group were asked to describe a negative incident involving their company, and answer a number of questions regarding how they felt about their company and how they behaved toward their company following the negative event. They also completed measures of organizational cynicism and job satisfaction. The two groups were compared on demographic characteristics and on their attitudes toward their organization. There were very few demographic differences between the two groups. The Internet group tended to be more cynical and to judge their organization more harshly than the non-Internet group; however, the response patterns of both groups were similar. These results suggest that, when used with caution, the Internet can be a viable method of conducting organizational research

Measuring the Circle: Emerging Trends in Philanthropy for First Nations

The Circle had the opportunity to undertake a multi-part research project to gain a more robust understanding of non-governmental funding to Aboriginal beneficiaries and causes in Canada over the past few years. The year-long knowledge gathering process included three inter-related activities: (a) mining Canada Revenue Agency data to map the Aboriginal funding economy in Canada from 2005 to 2011; (b) a set of Key Informant interviews with representatives from a sample of grantmakers surfaced through the mapping activity; and (c) a series of case studies to showcase some leading funders in the Aboriginal funding sphere or initiatives dedicated to building community capacity as well as supporting Aboriginal beneficiaries and causes. This report contains the key findings from the three-part research initiative