Hemostatic factors and risk of coronary heart disease in general populations: new prospective study and updated meta-analyses

<p>Background: Activation of blood coagulation and fibrinolysis may be associated with increased risk of coronary heart disease. We aimed to assess associations of circulating tissue plasminogen activator (t-PA) antigen, D-dimer and von Willebrand factor (VWF) with coronary heart disease risk.</p> <p>Design: Prospective case-control study, systematic review and meta-analyses.</p> <p>Methods: Measurements were made in 1925 people who had a first-ever nonfatal myocardial infarction or died of coronary heart disease during follow-up (median 19.4 years) and in 3616 controls nested within the prospective population-based Reykjavik Study.</p> <p>Results: Age and sex-adjusted odds ratios for coronary heart disease per 1 standard deviation higher baseline level were 1.25 (1.18, 1.33) for t-PA antigen, 1.01 (0.95, 1.07) for D-dimer and 1.11 (1.05, 1.18) for VWF. After additional adjustment for conventional cardiovascular risk factors, corresponding odds ratios were 1.07 (0.99, 1.14) for t-PA antigen, 1.06 (1.00, 1.13) for D-dimer and 1.08 (1.02, 1.15) for VWF. When combined with the results from previous prospective studies in a random-effects meta-analysis, overall adjusted odds ratios were 1.13 (1.06, 1.21) for t-PA antigen (13 studies, 5494 cases), 1.23 (1.16, 1.32) with D-dimer (18 studies, 6799 cases) and 1.16 (1.10, 1.22) with VWF (15 studies, 6556 cases).</p> <p>Conclusions: Concentrations of t-PA antigen, D-dimer and VWF may be more modestly associated with first-ever CHD events than previously reported. More detailed analysis is required to clarify whether these markers are causal risk factors or simply correlates of coronary heart disease.</p&gt

Zero-modes of Non-Abelian Solitons in Three Dimensional Gauge Theories

We study non-Abelian solitons of the Bogomol'nyi type in N=2 (d=2+1) supersymmetric Chern-Simons (CS) and Yang-Mills (YM) theory with a generic gauge group. In CS theory, we find topological, non-topological and semi-local (non-)topological vortices of non-Abelian kinds in unbroken, broken and partially broken vacua. We calculate the number of zero-modes using an index theorem and then we apply the moduli matrix formalism to realize the moduli parameters. For the topological solitons we exhaust all the moduli while we study several examples of the non-topological and semi-local solitons. We find that the zero-modes of the topological solitons are governed by the moduli matrix H_0 only and those of the non-topological solitons are governed by both H_0 and the gauge invariant field \Omega. We prove local uniqueness of the master equation in the YM case and finally, compare all results between the CS and YM theories.Comment: 54 pages, 1 figur

Study of an Alternate Mechanism for the Origin of Fermion Generations

In usual extended technicolor (ETC) theories based on the group ${\rm{SU}(N_{ETC}})_{ETC}$, the quarks of charge 2/3 and -1/3 and the charged leptons of all generations arise from ETC fermion multiplets transforming according to the fundamental representation. Here we investigate a different idea for the origin of SM fermion generations, in which quarks and charged leptons of different generations arise from ETC fermions transforming according to different representations of ${\rm{SU}(N_{ETC}})_{ETC}$. Although this mechanism would have the potential, {\it a priori}, to allow a reduction in the value of $N_{ETC}$ relative to conventional ETC models, we show that, at least in simple models, it is excluded by the fact that the technicolor sector is not asymptotically free or by the appearance of fermions with exotic quantum numbers which are not observed.Comment: 6 pages, late

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels. METHODS: The first 2296 participants (mean age 76+/-6 years, 42% men) in the Age, Gene/Environment Susceptibility-Reykjavik Study, a multidisciplinary epidemiological study to determine risk factors in aging, were genotyped for 10 single nucleotide polymorphisms (SNPs) in the CRP gene. General linear models with age and terms for interaction of CRP genotypes with BMI, waist circumference and percent fat were used to evaluate the association of genotypes to CRP levels (high-sensitivity method, range 0-10 mg l(-1)) in men and women separately. RESULTS: We focused on the SNP rs1205 that represents the allele that captures the strongest effects of the gene on CRP levels. Carriers of the rs1205 G allele had significantly higher CRP levels than noncarriers in a dose-dependent manner. Compared to the AA genotype, the slope of the increase in CRP with increasing BMI (P=0.045) and waist circumference (P=0.014) was different for the G allele carriers and of similar magnitude in both men and women. The rs1205 interactions were not significant for fat mass percent, suggesting a possible association with fat localization. CONCLUSIONS: This study further illuminates the known association between measures of adiposity and CRP levels and is shown to be dependent on variation in the rs1205 SNP of the CRP gene. The correlated increase in CRP levels with adiposity is accentuated by presence of the G allele

Group Theory of Non-Abelian Vortices

We investigate the structure of the moduli space of multiple BPS non-Abelian vortices in U(N) gauge theory with N fundamental Higgs fields, focusing our attention on the action of the exact global (color-flavor diagonal) SU(N) symmetry on it. The moduli space of a single non-Abelian vortex, CP(N-1), is spanned by a vector in the fundamental representation of the global SU(N) symmetry. The moduli space of winding-number k vortices is instead spanned by vectors in the direct-product representation: they decompose into the sum of irreducible representations each of which is associated with a Young tableau made of k boxes, in a way somewhat similar to the standard group composition rule of SU(N) multiplets. The K\"ahler potential is exactly determined in each moduli subspace, corresponding to an irreducible SU(N) orbit of the highest-weight configuration.Comment: LaTeX 46 pages, 4 figure

Unnatural Origin of Fermion Masses for Technicolor

We explore the scenario in which the breaking of the electroweak symmetry is due to the simultaneous presence and interplay of a dynamical sector and an unnatural elementary Higgs. We introduce a low energy effective Lagrangian and constrain the various couplings via direct search limits and electroweak and flavor precision tests. We find that the model we study is a viable model of dynamical breaking of the electroweak symmetry.Comment: 20 pages, 7 eps figure

Extreme Technicolor & The Walking Critical Temperature

We map the phase diagram of gauge theories of fundamental interactions in the flavor-temperature plane using chiral perturbation theory to estimate the relation between the pion decaying constant and the critical temperature above which chiral symmetry is restored. We then investigate the impact of our results on models of dynamical electroweak symmetry breaking and therefore on the electroweak early universe phase transition.Comment: RevTeX, 18 pages, 3 figure

Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R).

To access full text version of this article. Please click on the hyperlink "View/open" at the bottom of this pageWe aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. The study population consisted of 4,994 persons aged ≥ 67 years, who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA(1c) ≥ 6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA(1c), insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged.NIH N01-AG-12100 NIH/NIA, National Eye Institute (NEI) of the NIH ZIAEY000401, Hjartavernd (the Icelandic Heart Association), Althingi (the Icelandic Parliament), University of Iceland

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

Treatment as Prevention for Hepatitis C (TraP Hep C) - a nationwide elimination programme in Iceland using direct-acting antiviral agents

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879.Merck Astellas Gilead Gilead Sciences AbbVie BM