Cardiovascular tests: use & limits of biochemical markers - therapeutic measurements of ADMA involved in cardiovascular disorders

Asymmetric dimethylarginine (ADMA) is an endogenously occurring methylarginine that inhibits nitric oxide synthesis. Plasma levels of methylarginines increase in renal failure and certain cardiovascular pathologies, and in patients with end stage renal failure the level of ADMA predicts the risk of cardiovascular events and overall mortality. The object of this review is to describe the mechanisms of ADMA synthesis, metabolism and uptake and to outline techniques for measuring ADMA and the pathological states in which ADMA levels are altered

Universities, public research, and evolutionary economic geography

Evolutionary Economic Geography (EEG) has, thus far, neglected the contribution of universities to innovation processes in its emerging theoretical explanations of territorial economic change. This article begins to address this conceptual gap by outlining a perspective on the ways in which universities, as organizations with institutional features and functions that are distinctive to those of firms, can enhance the adaptive capacity of national or regional economies. The argument developed is based on a complexity theory view of system self-transformation and supports greater attention to this framework in a pluralistic EEG

Building collaborative platforms for urban innovation: Newcastle City Futures as a quadruple helix intermediary

There is a growing academic and policy interest in the notion of using cities as ‘living laboratories’ to develop and test responses to the social, environmental, and economic challenges present in contemporary urbanism. These living laboratories are often assumed to function through ‘quadruple helix’ relations between varied actors from the public, private, university, and community sectors. However, empirical research that explores the real-world functioning of these arrangements is comparatively limited. This paper will help address this gap through the case of Newcastle City Futures (NCF) – a university-anchored platform for collaborative urban foresight research, public engagement, and innovation. In particular, the paper will concentrate on a two year period when NCF focused on the facilitation of innovation demonstrator projects guided by the vision of Newcastle upon Tyne developing a post-industrial future as a ‘test-bed city’. Detailed empirical accounts of the development of two demonstrator projects are used to illustrate and analyse processes of cross-sectoral collaboration and engaging the public in co-design. These are used to support the conceptual argument that the presence of the quadruple helix as a form of local innovation system should not be taken as given. Instead the collaborative relationships required for transformational interventions in the future of cities need to be actively constructed by diverse actors and supported by intermediary vehicles such as NCF

Inflammation and endothelial function: Direct vascular effects of human C-reactive protein on nitric oxide bioavailability

Background - Circulating concentrations of the sensitive inflammatory marker C-reactive protein (CRP) predict future cardiovascular events, and CRP is elevated during sepsis and inflammation, when vascular reactivity may be modulated. We therefore investigated the direct effect of CRP on vascular reactivity. Methods and Results - The effects of isolated, pure human CRP on vasoreactivity and protein expression were studied in vascular rings and cells in vitro, and effects on blood pressure were studied in rats in vivo. The temporal relationship between changes in CRP concentration and brachial flow-mediated dilation was also studied in humans after vaccination with Salmonella typhi capsular polysaccharide, a model of inflammatory endothelial dysfunction. In contrast to some previous reports, highly purified and well-characterized human CRP specifically induced hyporeactivity to phenylephrine in rings of human internal mammary artery and rat aorta that was mediated through physiological antagonism by nitric oxide (NO). CRP did not alter endothelial NO synthase protein expression but increased protein expression of GTP cyclohydrolase-1, the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, the NO synthase cofactor. In the vaccine model of inflammatory endothelial dysfunction in humans, increased CRP concentration coincided with the resolution rather than the development of endothelial dysfunction, consistent with the vitro findings; however, administration of human CRP to rats had no effect on blood pressure. Conclusions - Pure human CRP has specific, direct effects on vascular function in vitro via increased NO production; however, further clarification of the effect, if any, of CRP on vascular reactivity in humans in vivo will require clinical studies using specific inhibitors of CRP. © 2005 American Heart Association, Inc

Moving boulders in flash floods and estimating flow conditions using boulders in ancient deposits

Boulders moving in flash floods cause considerable damage and casualties. More and bigger boulders move in flash floods than predicted from published theory. The interpretation of flow conditions from the size of large particles within flash flood deposits has, until now, generally assumed that the velocity (or discharge) is unchanging in time (i.e. flow is steady), or changes instantaneously between periods of constant conditions. Standard practice is to apply theories developed for steady flow conditions to flash floods, which are however inherently very unsteady flows. This is likely to lead to overestimates of peak flow velocity (or discharge). Flash floods are characterised by extremely rapid variations in flow that generate significant transient forces in addition to the mean-flow drag. These transient forces, generated by rapid velocity changes, are generally ignored in published theories, but they are briefly so large that they could initiate the motion of boulders. This paper develops a theory for the initiation of boulder movement due to the additional impulsive force generated by unsteady flow, and discusses the implications. Keywords

Risk of myocardial infarction and stroke after acute infection or vaccination.

BACKGROUND: There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. METHODS: We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. RESULTS: A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. CONCLUSIONS: Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events