Methods and Results. The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count.Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index.Conclusion. Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD. (Circulation 1991;83:836-844) N mumerous epidemiological studies1'2 have found raised blood pressure, elevated total cholesterol, and smoking to be major factors associated with an increased risk of ischemic heart disease (IHD). Nevertheless, on an individual basis, the prediction of the risk of IHD from levels of blood pressure, lipids, and smoking is poor.3 There is evidence4,5 that occlusive thrombi are to be found in almost all cases of acute myocardial infarction and in

a b s t r a c tThere is increasing interest in both relating the mechanical behavior of high-entropy alloys to their microstructural evolution and in their development for various applications. A special two-day international workshop on the above topic was held in Guiyang, China, in December 2014. The workshop gathered scientists and engineers to exchange information on recent progress in high-entropy alloys, to discuss the scientific issues and challenges to foster international collaborations, and to identify future directions. In this paper, a summary of this workshop is presented, including aspects of definition/terminology, phase formation, microstructure and phase stability, strengthening mechanisms, and hightemperature properties. Future research directions are also outlined. SynopsisThe continued development of high-performance materials is required for increased energy efficiency and sustainability. Traditionally, metallic alloys have been widely applied as structural materials. The conventional alloy design strategy usually is to start with one element as the principal constituent and adding other minor elements for the further optimization of properties and performances. After extensive efforts on these traditional alloys, the development of traditional alloys is approaching its limits. Recently, a new alloy design concept was proposed: the idea is to simultaneously alloy several principal elements (usually !5) to obtain high mixing entropy. As a result, many novel concentrated multicomponent alloys are in the process of being developed [1e6]. In a timely response to this rapid development, a two-day international workshop was held in Guiyang, PRC in December 2014 to exchange information on recent progress, foster international collaborations, and identify future research directions. The main theme of the workshop was the relationship between microstructures and mechanical properties. In this paper, a summary of this special workshop is presented, which includes; 1) Definition/terminology, 2) Main characteristics resulting from multiple primary constituents, 3) Atomic size effects on phase formation, 4) Microstructure and phase stability, 5) Strengthening mechanisms, 6) High-temperature mechanical properties, and 7) Future directions for research Definitions/terminologyAlthough "high-entropy alloys (HEAs)" have now become a new class of materials, the name has not been clearly defined since its inception. This often causes confusion in the scientific community.

A number of studies have shown total leukocyte count to be a risk factor for ischemic heart disease, but there is little information on the role of the individual types of leukocyte, and the role of smoking is controversial. The Caerphilly and Speedwell studies recruited 4,860 men aged 45-63 years between 1979 and 1983 in South Wales and the West of England, respectively. At the 10-year follow-up, the total leukocyte count predicted ischemic heart disease events after adjusting for the classical risk factors, including smoking. Five-year follow-up results were available for differential white cell counts. The main contributor to the increase in total count in the men who developed disease was the neutrophil count. There was also a statistically significant increase in the eosinophil count.

Objective-To assess the roles of plasma triglyceride and high density lipoprotein (HDL) cholesterol concentrations in predicting ischaemic heart disease.Design increased risk of ischaemic heart disease.5 The first British study, however, to report on this association concluded that HDL cholesterol was not a major risk factor.6 A later report, based on a larger number of events and with a different method of analysis, revised that view and concluded that HDL cholesterol was important, but less so than total cholesterol concentration.7Raised concentrations of total triglyceride are associated with an increased risk of ischaemic heart disease. Most studies suggest that, in men, triglyceride is not an independent risk factor and that its relation with ischaemic heart disease is explained by the association of both with other factors, particularly total cholesterol and HDL cholesterol.78 This, however, has not been a universal finding and the role of triglyceride is still uncertain.9 Understanding of this role is complicated by the fact that in some studies triglycerides were measured after the subjects had fasted overnight, whereas in others the subjects had not.The Caerphilly and Speedwell studies recruited their joint population of 4860 middle age men between 1979 and 1983.10 Lipids were measured on fasting blood samples. In this report, the relations of 60

Fibrinogen and viscosity are powerful, long term and independent predictors of the risk of ischaemic heart disease.

Aim-To examine the outcome of care for patients with glaucoma followed up by the hospital eye service compared with those followed up by community optometrists. Methods-A randomised study with patients allocated to follow up by the hospital eye service or community optometrists was carried out in the former county of Avon in south west England. 403 patients with established or suspected primary open angle glaucoma attending Bristol Eye Hospital and meeting defined inclusion and exclusion criteria were studied. The mean number of missed points on visual field testing in the better eye (using a "better/worse" eye analysis) in each group were measured. The visual field was measured using the Henson semiautomated central field analyser (CFA 3000). Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. The mean number of missed points on visual field testing in the worse eye, mean intraocular pressure (mm Hg), and cup disc ratio using a "better/worse" eye analysis in each group at 2 years were also measured. Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. An analysis of covariance comparing method of follow up taking into account baseline measurements of outcome variables was carried out. Additional control was considered for age, sex, diagnostic group (glaucoma suspect/established primary open angle glaucoma), and treatment (any/none). Results-From examination of patient notes, 2780 patients with established or suspected glaucoma were identified. Of these, 752 (27.1%) fulfilled the entry criteria. For hospital and community follow up group respectively, mean number of missed points on visual field testing at 2 year follow up for better eye was 7.9 points and 6.8 points; for the worse eye 20. Conclusions-It is feasible to set and run shared care schemes for a proportion of patients with suspected and established glaucoma using community optometrists. After 2 years (a relatively short time in the life of a patient with glaucoma), there were no marked or statistically significant diVerences in outcome between patients followed up in the hospital eye service or by community optometrists. Decisions to implement such schemes need to be based on careful consideration of the costs of such schemes and local circumstances, including geographical access and the current organisation of glaucoma care within the hospital eye service.

Objective-To measure the prevalence and incidence of intermittent claudication, to describe the mortality associated with the condition, and to assess the relevance of risk factors for vascular disease. Design-A standard questionnaire on calf pain when walking was given in the prospective Speedwell study, and a range of risk factors were measured. The men were re-examined at intervals of three years, and deaths over 11 years were identified. Setting-The general population. Participants-All men aged 45 to 59 registered with 16 general practitioners. Results-The prevalence of intermittent claudication increased from almost nil at ages 45-49 to 2'9% at ages 60-64. The annual incidence increased from 0-3% in the youngest men to 0'5% in those in their early 60s. Intermittent claudication was related to the existence of ischaemic heart disease, particularly angina, at the first examination. The relative odds of men with angina developing intermittent claudication was 6*7 (95% confidence interval (95% CI) 3-6 to 12.4). The risk of death in men with intermittent claudication was substantially raised. After standardisation for age and smoking the relative odds of death was 3.8 (95% CI 2'2 to 6.5). The excess was entirely from circulatory causes. Systolic blood pressure, fasting plasma glucose, triglycerides, and white cell count were all independently associated with the development of intermittent claudication, but the most striking association was with smoking. Conclusions--Intermittent claudication is an indicator for a very high risk of death. This is only pairtly explained by its strong association with ischaemic heart disease. (Br Heart3 1994;72:128-132)

BackgroundIt is unclear whether C-reactive protein (CRP) is causally related to coronary heart disease (CHD). Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864) and CHD risk in the largest study to date of this association.Methods and ResultsWe estimated the association of CRP genetic variant +1444C>T (rs1130864) with CRP levels and with CHD in five studies and then pooled these analyses (N = 18,637 participants amongst whom there were 4,610 cases). CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass) whereas genotype (rs1130864) was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95%CI: 1.06, 1.21), and after further adjustment for confounding factors it was 1.07 (95%CI: 1.02, 1.13). Genotype (rs1130864) was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95%CI: 1.15, 1.28) and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95%CI: 1.11, 1.18), with no strong evidence in either analyses of between study heterogeneity (I2 = 0%, p>0.9 for both analyses). There was no association of genotype (rs1130864) with CHD: pooled odds ratio 1.01 (95%CI: 0.88, 1.16) comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95%CI: 0.90, 1.03) per additional T allele (I2<7.5%, p>0.6 for both meta-analyses). An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD) suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95%CI: 0.61, 1.80).ConclusionsWe found no association of a genetic variant, which is known to be related to CRP levels, (rs1130864) and having CHD. These findings do not support a causal association between circulating CRP and CHD risk, but very large, extended, genetic association studies would be required to rule this out.