| 1. |
- Emerging Risk Factors, Collaboration, et al.
(författare)
-
The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
- 2007
-
Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
-
Tidskriftsartikel (refereegranskat)abstract
- Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
|
|
| 2. |
- Danesh, John, et al.
(författare)
-
Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis
- 2005
-
Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 294:14, s. 1799-1809
-
Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
|
|
| 3. |
- Shin, J. H., et al.
(författare)
-
IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
-
Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
-
Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
|
|
| 4. |
|
|
| 5. |
- Lamalle, P. U., et al.
(författare)
-
Expanding the operating space of ICRF on JET with a view to ITER
- 2006
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 46:2, s. 391-400
-
Tidskriftsartikel (refereegranskat)abstract
- This paper reports on ITER-relevant ion cyclotron resonance frequency (ICRF) physics investigated on JET in 2003 and early 2004. Minority heating of helium three in hydrogen plasmas-(He-3)H-was systematically explored by varying the 3 He concentration and the toroidal phasing of the antenna arrays. The best heating performance (a maximum electron temperature of 6.2 keV with 5 MW of ICRF power) was obtained with a preferential wave launch in the direction of the plasma current. A clear experimental demonstration was made of the sharp and reproducible transition to the mode conversion heating regime when the 3 He concentration increased above similar to 2%. In the latter regime the best heating performance (a maximum electron temperature of 8 keV with 5 MW of ICRF power) was achieved with dipole array phasing, i.e. a symmetric antenna power spectrum. Minority heating of deuterium in hydrogen plasmas-(D)H-was also investigated but was found inaccessible because this scenario is too sensitive to impurity ions with Z/A = 1/2 such as C6+, small amounts of which directly lead into the mode conversion regime. Minority heating of up to 3% of tritium in deuterium plasmas was systematically investigated during the JET trace tritium experimental campaign (TTE). This required operating JET at its highest possible magnetic field (3.9 to 4 T) and the ICRF system at its lowest frequency (23 MHz). The interest of this scenario for ICRF heating at these low concentrations and its efficiency at boosting the suprathermal neutron yield were confirmed, and the measured neutron and gammay ray spectra permit interesting comparisons with advanced ICRF code simulations. Investigations of finite Larmor radius effects on the RF-induced high-energy tails during second harmonic (omega = 2 omega(c)) heating of a hydrogen minority in D plasmas clearly demonstrated a strong decrease in the RF diffusion coefficient at proton energies similar to 1 MeV in agreement with theoretical expectations. Fast wave heating and current drive experiments in deuterium plasmas showed effective direct electron heating with dipole phasing of the antennas, but only small changes of the central plasma current density were observed with the directive phasings, in particular at low single pass damping. New investigations of the heating efficiency of ICRF antennas confirmed its strong dependence on the parallel wavenumber spectrum. Advances in topics of a more technological nature are also summarized: ELM studies using fast RF measurements, the successful experimental demonstration of a new ELM-tolerant antenna matching scheme and technical enhancements planned on the JET ICRF system for 2006, they being equally strongly driven by the preparation for ITER.
|
|
| 6. |
|
|
| 7. |
- Lamalle, P.U, et al.
(författare)
-
Expanding the operating space of ICRF on JET with a view to ITER
- 2006
-
Ingår i: Nucl. Fusion. ; 46, s. 391-
-
Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) has been used for millennia in many applications, primarily in artisanal mining and as an electrode in the chlor–alkali industry. It is anthropogenically emitted as a pollutant from coal fired power plants and naturally emitted, primarily from volcanoes. Its unique chemical characteristics enable global atmospheric transport and it is deposited after various processes, ultimately ending up in one of its final sinks, such as incorporated into deep sediment or bioaccumulated, primarily in the marine environment. All forms of Hg have been established as toxic, and there have been no noted biological benefits from the metal.Throughout time, there have been notable incidents of Hg intoxication documented, and the negative health effects have been documented to those chronically or acutely exposed. Today, exposure to Hg is largely diet or occupationally dependent, however, many are exposed to Hg from their amalgam fillings. This paper puts a tentative monetary value on Hg polluted food sources in the Arctic, where local, significant pollution sources are limited, and relates this to costs for strategies avoiding Hg pollution and to remediation costs of contaminated sites in Sweden and Japan. The case studies are compiled to help policy makers and the public to evaluate whether the benefits to the global environment from banning Hg and limiting its initial emission outweigh the benefits from its continued use or lack of control of Hg emissions. The cases we studied are relevant for point pollution sources globally and their remediation costs ranged between 2500 and 1.1 million US$ kg−1 Hg isolated from the biosphere. Therefore, regulations discontinuing mercury uses combined with extensive flue gas cleaning for all power plants and waste incinerators is cost effective.
|
|
| 8. |
- Agnelli, G, et al.
(författare)
-
Safety assessment of new antithrombotic agents : Lessons from the EXTEND study on ximelagatran.
- 2009
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 123:3, s. 488-497
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.
|
|
| 9. |
|
|
| 10. |
- Brucas, R., et al.
(författare)
-
Magnetic anisotropy and evolution of ground-state domain structures in bcc Fe81Ni19/Co(001) superlattices
- 2008
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : The American Physical Society. - 1098-0121 .- 1550-235X. ; 78:2, s. 024421-
-
Tidskriftsartikel (refereegranskat)abstract
- The magnetic anisotropy and evolution of striped magnetic domain structures in bcc Fe81Ni19/Co(001) superlattices with the total thickness ranging from 85 to 1370 nm has been studied by magneto-optical Kerr effect and magnetic force microscopy. At a thickness of about 85 nm [25 bilayers (BL)] the domains appear as stripe domains, typical for perpendicular anisotropy films, with the weak cubic anisotropy of the in-plane magnetization component stabilizing the stripe direction. The magnetic domain period strongly depends on the thickness of the superlattice. As the thickness increases, the equilibrium magnetization orients at oblique angles with respect to the film plane and continuously varies with the thickness from in-plane to out-of-plane. We first apply a simple phenomenological model which correctly predicts the transition from in-plane to out-of-plane magnetization as well as increasing domain period and saturation field with increasing BL number. The results indicate the presence of partial flux-closure domains at the film surface with the tilt angle continuously varying with the superlattice thickness. By solving a linearized Landau–Lifshitz equation together with Maxwell’s equations in magnetostatic approximation for samples consisting of up to 1000 individual layers, we calculate the spin-wave dispersion and determine the stability conditions for the saturated ferromagnetic state. From these results the dependence of the saturation field on the number of layers is inferred and agrees well with the experiment. The uniaxial bulk anisotropy is attributed to distortions along the c axis and the results further show evidence for the presence of an easy-plane interface anisotropy in these samples.
|
|
