Inflammatory markers as novel predictors of cardiovascular disease

Inflammation is widely considered to be an important contributing factor in atherogenesis and the risk of atherothrombotic complications. Baseline measurements of some inflammatory markers are known to be predictive risk factors for future cardiovascular disease (CVD) events in prospective epidemiological studies. Inflammatory markers dominant in the literature are acute phase response (APR)-associated and include fibrinogen, C-reactive protein (CRP) and, more recently, interleukin- (IL-) 6. This thesis reviews the literature and suggests the need for further research into novel inflammatory markers of CVD risk. The broad aim was to expand on limited existing data and ascertain if circulating levels of four novel inflammatory markers (tumour necrosis factor alpha [TNF alpha], IL-18, soluble CD40 ligand [sCD40L], and matrix metalloproteinase-9 [MMP-9]) are associated with classical cardiovascular risk factors, and with future CVD events in several epidemiological studies. In studies of pre-analytical variables, all four markers had commercially available assays acceptable for epidemiological use, but only IL-18 and TNF alpha displayed assay stability and the ability to be measured in plasma or serum. Due to limited serum samples, MMP-9 and sCD40L were less extensively measured. Results suggest a moderate positive association of MMP-9 with coronary heart disease (CHD) risk (although confounded by smoking and markers of general inflammation), while serum sCD40L may be moderately inversely related to CHD risk. More data is required for these markers. IL-18 and TNF alpha displayed similar degrees of short-term biological variability and regression dilution as CRP. Population distributions of both cytokines were consistent with limited previous reports. Both displayed associations with conventional vascular risk factors (such as age, gender, HDL cholesterol, and smoking), although interestingly, associations with epidemiological measures of obesity were poor. Both cytokines demonstrated moderate associations with vascular disease in a retrospective CHD study. In 3 prospective CHD or CVD studies, IL-18 demonstrated consistent but moderate associations with risk of vascular events in age- and sex-adjusted models (Odds ratio [OR]~1.6 in the top versus bottom third of the population). The association became borderline significant after adjustment for conventional risk markers. Associations of TNF alpha with risk of CHD in these studies were inconsistent, and more data are needed. In 3 prospective stroke studies, TNF alpha demonstrated some moderate associations with acute stroke outcome and recurrent stroke risk, but not with incident stroke in the elderly with vascular disease. IL-18 demonstrated no association with risk or outcome in any stroke study. Meta-analysis in 4 suitable prospective studies showed (in full adjustment models) that IL-18 (OR 1.18 [95% CI 0.95-1.48] comparing extreme thirds) and TNF alpha OR 1.05 [0.67-1.64]) have at best weak independent associations with CVD risk. Therefore these markers are unlikely to add significantly to clinical vascular risk prediction models, although these cytokines may still be of biological significance and potential therapeutic targets. More data is required for these markers. In conclusion IL-18, TNF alpha, MMP-9 and sCD40L may show weak associations with CVD. However, despite animal and tissue models indicating that they may play pivotal roles in atherogenesis, circulating concentrations of these inflammatory markers have limited independent vascular risk associations. Elevated circulating levels of APR-associated markers may sensitively reflect exposure to a wide range of adverse pro-inflammatory stimuli including lifestyle exposures, whereas some other inflammatory markers may not

The death of collective identity? Global movement as a parallelogram of forces.

yesThis paper brings together a number of theoretical and political interests we have with the concept of global movements and the alter-globalisation, anticapitalist, and social justice movements in particular (Chesters & Welsh, 2004, 2005, 2006). The argument contained in this paper is that these movements are the emergent outcome of complex processes of interaction, encounter and exchange facilitated and mediated by new technologies of mobility and communication and they suggest the emergence of a post-representational cultural politics qualitatively different from the identity based social movements of the past

Gas Absorption Detected from the Edge-on Debris Disk Surrounding HD32297

Near-infrared and optical imaging of HD32297 indicate that it has an edge-on debris disk, similar to beta Pic. I present high resolution optical spectra of the NaI doublet toward HD32297 and stars in close angular proximity. A circumstellar absorption component is clearly observed toward HD32297 at the stellar radial velocity, which is not observed toward any of its neighbors, including the nearest only 0.9 arcmin away. An interstellar component is detected in all stars >90 pc, including HD32297, likely due to the interstellar material at the boundary of the Local Bubble. Radial velocity measurements of the nearest neighbors, BD+07 777s and BD+07 778, indicate that they are unlikely to be physically associated with HD32297. The measured circumstellar column density around HD32997, log N(NaI) ~ 11.4, is the strongest NaI absorption measured toward any nearby main sequence debris disk, even the prototypical edge-on debris disk, beta Pic. Assuming that the morphology and abundances of the gas component around HD32297 are similar to beta Pic, I estimate an upper limit to the gas mass in the circumstellar disk surrounding HD32297 of ~0.3 M_Earth.Comment: 13 pages, 2 figures; Accepted for publication in ApJ Letter

Analysis of complete positivity conditions for quantum qutrit channels

We present an analysis of complete positivity (CP) constraints on qutrit quantum channels that have a form of affine transformations of generalized Bloch vector. For diagonal (damping) channels we derive conditions analogous to the ones that in qubit case produce tetrahedron structure in the channel parameter space.Comment: 12 pages, 8 figures (.eps), minor changes in the text and formula

Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells - Activation of protein kinase B by wortmannin-sensitive and -insensittve mechanisms

Previous studies using L6 myotubes have suggested that glycogen synthase kinase-3 (GSK-3) is phosphoryl ated and inactivated in response to insulin by protein kinase B (PKB, also known as Akt or RAG) (Cross, D, A, E., Alessi, D, R., Cohen, P., Andjelkovic, M., and Hemmings, B, A. (1995) Nature 378, 785-789), In the present study, marked increases in the activity of PKB have been shown to occur in insulin-treated rat epididymal fat cells with a time course compatible with the observed decrease in GSK-3 activity, Isoproterenol, acting primarily through beta(3)-adrenoreceptors, was found to decrease GSK-3 activity to a similar extent (approximately 50%) to insulin, However, unlike the effect of insulin, the inhibition of GSK by isoproterenol was not found to be sensitive to inhibition by the phosphatidylinositol 3'-kinase inhibitors, wortmannin or LY 294002, The change in GSK-3 activity brought about by isoproterenol could not be mimicked by the addition of permeant cyclic AMP analogues or forskolin to the cells, although at the concentrations used, these agents were able to stimulate lipolysis. Isoproterenol, but again not the cyclic AMP analogues, was found to increase the activity of PKB, although to a lesser extent than insulin. While wortmannin abolished the stimulation of PKB activity by insulin, it was without effect on the activation seen in response to isoproterenol, The activation of PKB by isoproterenol was not accompanied by any detectable change in the electrophoretic mobility of the protein on SDS-polyacrylamide gel electrophoresis. It would therefore appear that distinct mechanisms exist for the stimulation of PKB by insulin and isoproterenol in rat fat cells

Using Geographic Information Systems to investigate variations in accessibility to ‘extended hours’ primary healthcare provision

There are ongoing policy concerns surrounding the difficulty in obtaining timely appointments to primary healthcare services and the potential impact on, for example, attendance at accident and emergency services and potential health outcomes. Using the case study of potential access to primary healthcare services in Wales, Geographic Information System (GIS)‐based tools that permit a consideration of population‐to‐provider ratios over space are used to examine variations in geographical accessibility to general practitioner (GP) surgeries offering appointment times outside of ‘core’ operating hours. Correlation analysis is used to explore the association of accessibility scores with potential demand for such services using UK Population Census data. Unlike the situation in England, there is a tendency for accessibility to those surgeries offering ‘extended’ hours of appointment times to be better for more deprived census areas in Wales. However, accessibility to surgeries offering appointments in the evening was associated with lower levels of working age population classed as ‘economically active’; that is, those who could be targeted beneficiaries of policies geared towards ‘extended’ appointment hours provision. Such models have the potential to identify spatial mismatches of different facets of primary healthcare, such as ‘extended’ hours provision available at GP surgeries, and are worthy of further investigation, especially in relation to policies targeted at particular demographic groups

N-terminal pro-B-type natriuretic peptide and the prediction of primary cardiovascular events: results from 15-year follow-up of WOSCOPS

<b>Aims:</b>To test whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) was independently associated with, and improved the prediction of, cardiovascular disease (CVD) in a primary prevention cohort. <b>Methods and results:</b> In the West of Scotland Coronary Prevention Study (WOSCOPS), a cohort of middle-aged men with hypercholesterolaemia at a moderate risk of CVD, we related the baseline NT-proBNP (geometric mean 28 pg/mL) in 4801 men to the risk of CVD over 15 years during which 1690 experienced CVD events. Taking into account the competing risk of non-CVD death, NT-proBNP was associated with an increased risk of all CVD [HR: 1.17 (95% CI: 1.11–1.23) per standard deviation increase in log NT-proBNP] after adjustment for classical and clinical cardiovascular risk factors plus C-reactive protein. N-terminal pro-B-type natriuretic peptide was more strongly related to the risk of fatal [HR: 1.34 (95% CI: 1.19–1.52)] than non-fatal CVD [HR: 1.17 (95% CI: 1.10–1.24)] (P= 0.022). The addition of NT-proBNP to traditional risk factors improved the C-index (+0.013; P < 0.001). The continuous net reclassification index improved with the addition of NT-proBNP by 19.8% (95% CI: 13.6–25.9%) compared with 9.8% (95% CI: 4.2–15.6%) with the addition of C-reactive protein. N-terminal pro-B-type natriuretic peptide correctly reclassified 14.7% of events, whereas C-reactive protein correctly reclassified 3.4% of events. Results were similar in the 4128 men without evidence of angina, nitrate prescription, minor ECG abnormalities, or prior cerebrovascular disease. <b>Conclusion:</b> N-terminal pro-B-type natriuretic peptide predicts CVD events in men without clinical evidence of CHD, angina, or history of stroke, and appears related more strongly to the risk for fatal events. N-terminal pro-B-type natriuretic peptide also provides moderate risk discrimination, in excess of that provided by the measurement of C-reactive protein

Discovery of 15-second oscillations in Hubble Space Telescope observations of WZ Sagittae following the 2001 outburst

We report the discovery of 15-s oscillations in ultraviolet observations of WZ Sge obtained with the Hubble Space Telescope approximately one month after the peak of the 2001 outburst. This is the earliest detection of oscillations in WZ Sge following an outburst and the first time that a signal near 15 s has been seen to be dominant. The oscillations are quite strong (amplitude about 5%), but not particularly coherent. In one instance, the oscillation period changed by 0.7 s between successive observations separated by less than 1 hour. We have also found evidence for weaker signals with periods near 6.5 s in some of our data. We discuss the implications of our results for the models that have been proposed to account for the 28-s oscillations seen in quiescence. If the periods of the 15-s oscillations can be identified with the periods of revolution of material rotating about the white dwarf, the mass of the white dwarf must satisfy M_WD > 0.71 M_sun. The corresponding limit for the 6.5-s signals is M_WD > 1.03 M_sun.Comment: accepted for publication in ApJ Letters; 13 pages, 4 postscript figures; new version corrects a few typos and matches version that will appear in ApJ