Contribution of 30 Biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: The MONICA, risk, genetics, archiving and monograph (MORGAM) biomarker project

Background— Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study.
Methods and Results— Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (P=0.004) and integrated discrimination (P<0.0001) and led to significant reclassification of individuals into risk categories (P=0.0008).
Conclusions— The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups.

Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations

Background. From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates, across the populations. Methods. In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. Findings. Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, body-mass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. Interpretation. Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort

Aims
Our aim was to test the prediction and clinical applicability of high-sensitivity assayed troponin I for incident cardiovascular events in a general middle-aged European population.

Methods and results
High-sensitivity assayed troponin I was measured in the Scottish Heart Health Extended Cohort (n = 15 340) with 2171 cardiovascular events (including acute coronary heart disease and probable ischaemic strokes), 714 coronary deaths (25% of all deaths), 1980 myocardial infarctions, and 797 strokes of all kinds during an average of 20 years follow-up. Detection rate above the limit of detection (LoD) was 74.8% in the overall population and 82.6% in men and 67.0% in women. Troponin I assayed by the high-sensitivity method was associated with future cardiovascular risk after full adjustment such as that individuals in the fourth category had 2.5 times the risk compared with those without detectable troponin I (P < 0.0001). These associations remained significant even for those individuals in whom levels of contemporary-sensitivity troponin I measures were not detectable. Addition of troponin I levels to clinical variables led to significant increases in risk prediction with significant improvement of the c-statistic (P < 0.0001) and net reclassification (P < 0.0001). A threshold of 4.7 pg/mL in women and 7.0 pg/mL in men is suggested to detect individuals at high risk for future cardiovascular events.

Conclusion
Troponin I, measured with a high-sensitivity assay, is an independent predictor of cardiovascular events and might support selection of at risk individuals.

Cardiovascular disease risk profiles among 'healthy' siblings of patients with early-onset cardiovascular disease:Application of the new SCORE system

BACKGROUND: Cardiovascular disease (CVD) occurs more frequently in individuals with a family history of premature CVD. Within families the demographics of CVD are poorly described. DESIGN: We examined the risk estimation based on the Systematic Coronary Risk Evaluation (SCORE) system and the Joint British Guidelines (JBG) for older unaffected siblings of patients with premature CVD (onset ≤55 years for men and ≤60 years for women). METHODS: Between August 1999 and November 2003 laboratory and demographic details were collected on probands with early-onset CVD and their older unaffected siblings. Siblings were screened for clinically overt CVD by a standard questionnaire and 12-lead electrocardiogram (ECG). RESULTS: A total of 790 siblings was identified and full demographic details were available for 645. The following siblings were excluded: 41 with known diabetes mellitus; seven with random plasma glucose of 11.1 mmol/l or greater; and eight with ischaemic ECG. Data were analysed for 589 siblings from 405 families. The mean age was 55.0 years, 43.1% were men and 28.7% were smokers. The mean total serum cholesterol was 5.8 mmol/l and hypertension was present in 49.4%. Using the SCORE system, when projected to age 60 years, 181 men (71.3%) and 67 women (20.0%) would be eligible for risk factor modification. Using JBG with a 10-year risk of 20% or greater, 42 men (16.5%) and four women (1.2%) would be targeted. CONCLUSIONS: Large numbers of these asymptomatic individuals meet both European and British guidelines for the primary prevention of CVD and should be targeted for risk factor modification. The prevalence of individuals defined as eligible for treatment is much higher when using the SCORE system. © 2007 European Society of Cardiology.

Estimation of survival rate and extinction probability for stage-structured populations with overlapping life stages

The development of methods providing reliable estimates of demographic parameters (e. g., survival rates, fecundity) for wild populations is essential to better understand the ecology and conservation requirements of individual species. A number of methods exist for estimating the demographics of stage-structured populations, but inherent mathematical complexity often limits their uptake by conservation practitioners. Estimating survival rates for pond-breeding amphibians is further complicated by their complex migratory and reproductive behaviours, often resulting in nonobservable states and successive cohorts of eggs and tadpoles. Here we used comprehensive data on 11 distinct breeding toad populations (Bufo calamita) to clarify and assess the suitability of a relatively simple method [the Kiritani-Nakasuji-Manly (KNM) method] to estimate the survival rates of stage-structured populations with overlapping life stages. The study shows that the KNM method is robust and provides realistic estimates of amphibian egg and larval survival rates for species in which breeding can occur as a single pulse or over a period of several weeks. The study also provides estimates of fecundity for seven distinct toad populations and indicates that it is essential to use reliable estimates of fecundity to limit the risk of under- or overestimating the survival rates when using the KNM method. Survival and fecundity rates for B. calamita populations were then used to define population matrices and make a limited exploration of their growth and viability. The findings of the study recently led to the implementation of practical conservation measures at the sites where populations were most vulnerable to extinction. © 2010 The Society of Population Ecology and Springer.

Effect of cooking method and rice type on arsenic concentration in cooked rice and the estimation of arsenic dietary intake in a rural village in West Bengal, India

Arsenic (As) contamination of rice plants can result in high total As concentrations (t-As) in cooked rice, especially if As-contaminated water is used for cooking. This study examines two variables: (1) the cooking method (water volume and inclusion of a washing step); and (2) the rice type (atab and boiled). Cooking water and raw atab and boiled rice contained 40 g As l-1 and 185 and 315 g As kg-1, respectively. In general, all cooking methods increased t-As from the levels in raw rice; however, raw boiled rice decreased its t-As by 12.7% when cooked by the traditional method, but increased by 15.9% or 23.5% when cooked by the intermediate or contemporary methods, respectively. Based on the best possible scenario (the traditional cooking method leading to the lowest level of contamination, and the atab rice type with the lowest As content), t-As daily intake was estimated to be 328 g, which was twice the tolerable daily intake of 150 g.

Contribution of water and cooked rice to an estimation of the dietary intake of inorganic arsenic in a rural village of West Bengal, India

Arsenic contamination of rice plants by arsenic-polluted irrigation groundwater could result in high arsenic concentrations in cooked rice. The main objective of the study was to estimate the total and inorganic arsenic intakes in a rural population of West Bengal, India, through both drinking water and cooked rice. Simulated cooking of rice with different levels of arsenic species in the cooking water was carried out. The presence of arsenic in the cooking water was provided by four arsenic species (arsenite, arsenate, methylarsonate or dimethylarsinate) and at three total arsenic concentrations (50, 250 or 500 mu g l(-1)). The results show that the arsenic concentration in cooked rice is always higher than that in raw rice and range from 227 to 1642 mu g kg(-1). The cooking process did not change the arsenic speciation in rice. Cooked rice contributed a mean of 41% to the daily intake of inorganic arsenic. The daily inorganic arsenic intakes for water plus rice were 229, 1024 and 2000 mu g day(-1) for initial arsenic concentrations in the cooking water of 50, 250 and 500 g arsenic l(-1), respectively, compared with the tolerable daily intake which is 150 mu g day(-1).

The Effects of Lead Sources on Oral Bioaccessibility in Soil and Implications for Contaminated Land Risk Management

Lead (Pb) is a non-threshold toxin capable of inducing toxic effects at any blood level but availability of soil screening criteria for assessing potential health risks is limited. The oral bioaccessibility of Pb in 163 soil samples was attributed to sources through solubility estimation and domain identification. Samples were extracted following the Unified BARGE Method. Urban, mineralisation, peat and granite domains accounted for elevated Pb concentrations compared to rural samples. High Pb solubility explained moderate-high gastric (G) bioaccessible fractions throughout the study area. Higher maximum G concentrations were measured in urban (97.6 mg kg−1) and mineralisation (199.8 mg kg−1) domains. Higher average G concentrations occurred in mineralisation (36.4 mg kg−1) and granite (36.0 mg kg−1) domains. Findings suggest diffuse anthropogenic and widespread geogenic contamination could be capable of presenting health risks, having implications for land management decisions in jurisdictions where guidance advises these forms of pollution should not be regarded as contaminated land.

Real-time temperature estimation for power MOSFETs considering thermal aging effects

This paper presents a novel real-time power-device temperature estimation method that monitors the power MOSFET's junction temperature shift arising from thermal aging effects and incorporates the updated electrothermal models of power modules into digital controllers. Currently, the real-time estimator is emerging as an important tool for active control of device junction temperature as well as online health monitoring for power electronic systems, but its thermal model fails to address the device's ongoing degradation. Because of a mismatch of coefficients of thermal expansion between layers of power devices, repetitive thermal cycling will cause cracks, voids, and even delamination within the device components, particularly in the solder and thermal grease layers. Consequently, the thermal resistance of power devices will increase, making it possible to use thermal resistance (and junction temperature) as key indicators for condition monitoring and control purposes. In this paper, the predicted device temperature via threshold voltage measurements is compared with the real-time estimated ones, and the difference is attributed to the aging of the device. The thermal models in digital controllers are frequently updated to correct the shift caused by thermal aging effects. Experimental results on three power MOSFETs confirm that the proposed methodologies are effective to incorporate the thermal aging effects in the power-device temperature estimator with good accuracy. The developed adaptive technologies can be applied to other power devices such as IGBTs and SiC MOSFETs, and have significant economic implications. 

Non-parametric bill of quantities estimation of concrete road bridges' superstructure: an artificial neural networks approach

Bridge construction responds to the need for environmentally friendly design of motorways and facilitates the passage through sensitive natural areas and the bypassing of urban areas. However, according to numerous research studies, bridge construction presents substantial budget overruns. Therefore, it is necessary early in the planning process for the decision makers to have reliable estimates of the final cost based on previously constructed projects. At the same time, the current European financial crisis reduces the available capital for investments and financial institutions are even less willing to finance transportation infrastructure. Consequently, it is even more necessary today to estimate the budget of high-cost construction projects -such as road bridges- with reasonable accuracy, in order for the state funds to be invested with lower risk and the projects to be designed with the highest possible efficiency. In this paper, a Bill-of-Quantities (BoQ) estimation tool for road bridges is developed in order to support the decisions made at the preliminary planning and design stages of highways. Specifically, a Feed-Forward Artificial Neural Network (ANN) with a hidden layer of 10 neurons is trained to predict the superstructure material quantities (concrete, pre-stressed steel and reinforcing steel) using the width of the deck, the adjusted length of span or cantilever and the type of the bridge as input variables. The training dataset includes actual data from 68 recently constructed concrete motorway bridges in Greece. According to the relevant metrics, the developed model captures very well the complex interrelations in the dataset and demonstrates strong generalisation capability. Furthermore, it outperforms the linear regression models developed for the same dataset. Therefore, the proposed cost estimation model stands as a useful and reliable tool for the construction industry as it enables planners to reach informed decisions for technical and economic planning of concrete bridge projects from their early implementation stages.