Measuring wall shear stress distribution in the carotid artery in an African population: Computational fluid dynamics versus ultrasound doppler velocimetry.

INTRODUCTION: Computational fluid dynamics (CFD) and ultrasound Doppler velocimetry are diagnostic tools useful for determining carotid artery segments susceptible to atheromatous plaque development. This study computes and compares the difference in Wall Shear Stress (WSS) measurements between these two methods. METHODS: The carotid artery of 204 volunteers selected using simple random sampling were scanned using standard carotid doppler protocols. Four segments of the carotid artery - the common, internal, external carotid, and the carotid bulb were sonographically assessed. The intima-media thickness, diameter, peak systolic velocity, and end-diastolic velocity were measured at a point 2 cm away from the carotid bifurcation for the three segments, while the carotid bulb was measured at the bifurcation. A 2D incompressible Navier-Stokes Equation for modelling Newtonian, pulsatile, and laminar flow in a viscoelastic pipe was applied to model velocity flow across the carotid artery using COMSOL software. WSS values were computed for experimental and CFD measurements and the results were compared. RESULTS: The WSS values generated by the model had respectively peak and average values of 19.81 N/cm2 and 15.76 ± 1.81 N/cm2 for the common carotid, 10.77 N/cm2 and 7.57 ± 1.66 N/cm2 for the internal carotid, 11.51 N/cm2 and 8.05 ± 1.65 N/cm2 for the external carotid, 37.55 N/cm2 and 26.55 ± 6.62 N/cm2 for the carotid bifurcation, 1.39 N/cm2 and 3.13 ± 1.34 N/cm2 for the carotid bulb. The model measurements matched doppler velocimetry measurements with <15% variation. CONCLUSION: Model based WSS values were higher but comparable with doppler velocimetry measurements. The carotid bulb had low WSS and is therefore the segment highly disposed to atheromatous plaque formation. IMPLICATIONS FOR PRACTICE: Subject-specific mathematical models could be incorporated during cardiovascular scan work up for accurate WSS distribution and early prediction of possible atherosclerotic sites.

Obesity and muscle strength as long-term determinants of all-cause mortality--a 33-year follow-up of the Mini-Finland Health Examination Survey.

OBJECTIVE: To examine the independent and combined associations of obesity and muscle strength with mortality in adult men and women. DESIGN: Follow-up study with 33 years of mortality follow-up. SUBJECTS: A total of 3594 men and women aged 50-91 years at baseline with 3043 deaths during the follow-up. MEASUREMENT: Body mass index (BMI) and handgrip strength were measured at baseline. RESULTS: Based on Cox models adjusted for age, sex, education, smoking, alcohol use, physical activity and chronic conditions, baseline obesity (BMI ≥30 kg m(-2)) was associated with mortality among participants aged 50-69 years (hazard ratio (HR) 1.14, 95% confidence interval (CI), 1.01-1.28). Among participants aged 70 years and older, overweight and obesity were protective (HR 0.77, 95% CI, 0.66-0.89 and HR 0.76, 95% CI, 0.62-0.92). High handgrip strength was inversely associated with mortality among participants aged 50-69 (HR 0.89, 95% CI, 0.80-1.00) and 70 years and older (HR 0.78, 95% CI, 0.66-0.93). Compared to normal-weight participants with high handgrip strength, the highest mortality risk was observed among obese participants with low handgrip strength (HR 1.23, 95% CI, 1.04-1.46) in the 50-69 age group and among normal-weight participants with low handgrip strength (HR 1.30, 95% CI, 1.09-1.54) among participants aged 70+ years. In addition, in the old age group, overweight and obese participants with high handgrip strength had significantly lower mortality than normal-weight participants with high handgrip strength (HR 0.79, 95% CI, 0.67-0.92 and HR 0.77, 95% CI, 0.63-0.94). CONCLUSION: Both obesity and low handgrip strength, independent of each other, predict the risk of death in adult men and women with additive pattern. The predictive value of obesity varies by age, whereas low muscle strength predicts mortality in all age groups aged>50 years and across all BMI categories. When promoting health among older adults, more attention should be paid to physical fitness in addition to body weight and adiposity.

Black-white differences in avoidable mortality in the USA, 1980-2005.

BACKGROUND: Avoidable Mortality (AM) describes causes of death that should not occur in the presence of high-quality and timely medical treatment and from causes that can be influenced at least in part by public policy/behaviour. This study analyses black-white disparities in AM. METHODS: Mortality under age 65 was analysed from: (1) conditions amenable to medical care; (2) those sensitive to public policy and/or behaviour change; (3) ischaemic heart disease; (4) HIV/AIDS; and (5) the remaining causes of death. Age-standardised death rates (ASDRs) were constructed for each race and sex group using vital statistics and census data from 1980-2005. Absolute rate differences and the proportionate contribution of each cause of death group to all-cause black-white mortality disparities are calculated based on the ASDRs. Negative binomial regression was used to model relative risks of death. RESULTS: In 2005, medical care amenable mortality was the largest source of absolute black-white mortality disparity, contributing 30% of the black-white difference in all-cause mortality among men and 42% among women; mortality subject to policy/behaviour interventions contributed 20% of the black-white difference for men and 4% for women. Although absolute black-white differences for most conditions diminished over time, relative disparities as measured by rate ratios showed little change, except for HIV/AIDS for which relative risks increased substantially for black men and women. CONCLUSIONS: There is considerable potential for narrowing of the black-white difference in AM, especially from causes amenable to medical care and (for men) policy/behaviour interventions.

Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform.

In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.

New African American life tables from 1935-1940 to 1985-1990.

New life tables for African Americans are presented from 1935 through 1990. They are based on a historical series of vital statistics data on deaths that have been corrected for age misreporting, on reconstructed population counts that have been adjusted for census underenumeration, and on births that have been corrected for underregistration. The new life tables show rapid mortality declines for both African American males and females from 1935 to 1950, and relatively steady reductions thereafter for females. The smaller declines in male mortality in young adulthood and middle age since the 1950s have led to exceptionally high ratios of male to female mortality at these ages. Corrections for census undercounts lead to higher values of life expectancy than in official life tables, but to less improvement over time. Official estimates of life expectancy at age 65 appear to be about 10% too high around 1940 but only about 1.5% too high in the late 1980s.

New insights into the Far Eastern pattern of mortality.

Some of the highest levels of excess mortality of males found anywhere in the world were present in several Far Eastern populations during the 1960s and 1970s but have progressively disappeared since that time. This study uses cause-of-death data to determine the diseases responsible for the existence and attenuation of these sex differences in Hong Kong, Singapore, and Taiwan. The results indicate that respiratory tuberculosis is the single most important underlying cause of the existence and attenuation of the pattern, that the role of liver diseases is not clear cut, and that other causes (such as cardiovascular diseases) are also important. A review of numerous risk factors yields no compelling reason why these populations experienced such large sex differences in mortality. However, it seems likely that public health and biomedical improvements (particularly those related to the reduction in mortality from tuberculosis) played a critical role in the attenuation of the Far Eastern mortality pattern.

Suppression of Fas/APO-1-mediated apoptosis by mitogen-activated kinase signaling.

Jurkat T cells undergo rapid apoptosis upon stimulation of the Fas/APO-1 (CD95) receptor. We examined the role of the mitogen-activated protein kinase (MAPK) cascade as a negative regulator of Fas-mediated apoptosis. To this end, we used both physiologic and artificial activators of MAPK, all of which activate MAPK by distinct routes. MAPK activity could be efficiently elevated by two T cell mitogens, the lectin PHA and an agonistic Ab to the T cell receptor complex as well as by the type 1 and 2A phosphatase inhibitor, calyculin A, and the protein kinase C-activating phorbol ester, tetradecanoyl phorbol acetate. All these treatments were effective in preventing the characteristic early and late features of Fas-mediated apoptosis, including activation of caspases. Our results indicate that the elevated MAPK activities intervene upstream of caspase activation. The degree of MAPK activation by the different stimuli used in our study corresponds well to their potency to inhibit apoptosis, indicating that MAPK activation serves as an efficient modulator of Fas-mediated apoptosis. The role of MAPK in modulation of Fas-mediated apoptosis was further corroborated by transient transfection with constitutively active MAPK kinase, resulting in complete inhibition of the Fas response, whereas transfection with a dominant negative form of MAPK kinase had no effect. Furthermore, the apoptosis inhibitory effect of the MAPK activators could be abolished by the specific MAPK kinase inhibitor PD 098059. Modulation of Fas responses by MAPK signaling may determine the persistence of an immune response and may explain the insensitivity of recently activated T cells to Fas receptor stimulation.

Reconstructing the size of the African American population by age and sex, 1930-1990.

We estimate the size of the African American population in five-year age groups at census dates from 1930 to 1990 using a three-part strategy. For cohorts born after 1935, we follow the U.S. Census Bureau in using classical demographic analysis. To estimate the size of cohorts born before 1895, we use extinct-generation estimates. For remaining cohorts, we implement an age/period/cohort model of census counts. All approaches are applied to a data set in which the age distribution of deaths has been corrected for age misreporting. Results provide strong confirmation of the basic validity of Census Bureau estimates of census undercounts for African Americans while extending estimates to new cohorts and periods. Our estimates are less consistent with an historical series prepared by Coale and Rives (1973).

Enhancement of fibroblast collagenase (matrix metalloproteinase-1) gene expression by ceramide is mediated by extracellular signal-regulated and stress-activated protein kinase pathways.

Inflammatory cytokines tumor necrosis factor-alpha and interleukin-1 trigger the ceramide signaling pathway, initiated by neutral sphingomyelinase-elicited hydrolysis of cell membrane phospholipid sphingomyelin to ceramide, a new lipid second messenger. Here, we show that triggering the ceramide pathway by sphingomyelinase or C2- and C6-ceramide enhances collagenase-1 (matrix metalloproteinase-1; MMP-1) gene expression by fibroblasts. C2-ceramide activates three distinct mitogen-activated protein kinases (MAPKs) in dermal fibroblasts, i.e. extracellular signal-regulated kinase 1/2 (ERK1/2), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Stimulation of MMP-1 promoter activity by C2-ceramide is dependent on the presence of a functional AP-1 cis-element and is entirely inhibited by overexpression of MAPK inhibitor, dual specificity phosphatase CL100 (MAPK phosphatase-1). Activation of MMP-1 promoter by C2-ceramide is also effectively inhibited by kinase-deficient forms of ERK1/2 kinase (MEK1/2) activator Raf-1, ERK1 and ERK2, SAPK/JNK activator SEK1, or SAPKbeta. In addition, ceramide-dependent induction of MMP-1 expression is potently prevented by PD 98059, a selective inhibitor of MEK1 activation, and by specific p38 inhibitor SB 203580. These results show that triggering the ceramide signaling pathway activates MMP-1 gene expression via three distinct MAPK pathways, i.e. ERK1/2, SAPK/JNK, and p38, and suggest that targeted modulation of the ceramide signaling pathway may offer a novel therapeutic approach for inhibiting collagenolytic activity, e.g. in inflammatory disorders.

Cause-specific mortality among older African-Americans: correlates and consequences of age misreporting.

This paper examines the quality of age reporting on death certificates of elderly African-Americans by major causes of death. We utilize a sample of death certificates linked to early census records and to Social Security Administration records to establish a "true" age at death. We then examine the patterns, predictors, and consequences of age misreporting for major causes of death. We find a pattern of greater age misreporting among females, identify educational background as a key predictor of accurate age reporting, and show that mortality crossovers are eliminated for most causes of death when more accurate age data are used.

African-American mortality at older ages: results of a matching study.

In this paper we investigate the quality of age reporting on death certificates of elderly African-Americans. We link a sample of death certificates of persons age 65+ in 1985 to records for the same individuals in U.S. censuses of 1900, 1910, and 1920 and to records of the Social Security Administration. The ages at death reported on death certificates are too young on average. Errors are greater for women than for men. Despite systematic under-reporting of age at death, too many deaths are registered at ages 95+. This excess reflects an age distribution of deaths that declines steeply with age, so that the base for upward transfers into an age category is much larger than the base for the transfers downward and out. When corrected ages at death are used to estimate age-specific death rates, African-American mortality rates increase substantially above age 85 and the racial "crossover" in mortality disappears. Uncertainty about white rates at ages 95+, however, prevents a decisive racial comparison at the very oldest ages.

Educational differentials in mortality: United States, 1979-85.

The paper examines educational differentials in adult mortality in the United States within a multivariate framework using data from the National Longitudinal Mortality Survey (NLMS). As a preliminary step we compare the magnitude of educational mortality differentials in the United States to those documented in Europe. At ages 35-54, the proportionate reductions in mortality for each one year increase in schooling are similar in the United States to those documented in Europe. The analyses further reveal significant educational differentials in U.S. mortality among both men and women in the early 1980s. Differentials are larger for men and for working ages than for women and persons age 65 and above. These differentials persist but are reduced in magnitude when controls for income, marital status and current place of residence are introduced.

Are educational differentials in adult mortality increasing in the United States?

Two recent studies have compared the size of educational mortality differentials among adults in the 1980s to estimates for 1960. Both studies have concluded that educational differentials have increased for males. One study finds a similar increase for females. We reconsider this question by introducing a data source that is better suited to estimating recent differentials than either of the two that have been employed. We also evaluate the quality of the 1960 baseline estimates and introduce broader measures of inequality. We conclude that educational inequalities have widened for males but contracted for working-age females. For both sexes, inequality trends are more adverse for persons aged 65+ than for persons aged 25-64. The role of national health insurance in shaping these trends is briefly considered.

Estimating African-American mortality from inaccurate data.

This paper evaluates the quality of vital statistics and census data for estimating African-American mortality over a period of six decades. The authors employ intercensal cohort comparisons and extinct generation estimates to demonstrate that conventionally constructed African-American death rates may be seriously flawed as early as age 50. Using the crude death rate at ages 50+ for 1978-1982 in conjunction with estimated growth rates and two model life table systems, the authors estimate black age-specific death rates in 1978-1982. These results suggest that if a racial crossover in death rates occurs, the age pattern of mortality among African-Americans must be far outside the range observed in populations with more accurate data.

Changes in breastfeeding initiation and duration in Peru, 1977-1986.

Both breastfeeding initiation and duration increased in Peru during 1977-86. Although one would have expected that the average incidence and duration of breastfeeding would have declined as a result of changes in population characteristics, the potential for an overall decline was more than overcome by changes in behavior. A net increase in initiation and duration is shown for all subgroups of interest. The largest absolute increases are documented for children who, in 1977, were the least likely to be breastfed and who were breastfed for the shortest durations.

PIP: Demographers compared current-status data on 3560 surviving singleton live births born to ever married women in Peru (1977-1978 World Fertility Survey) with 816 such births (1986 Demographic and Health Surveys) to examine changes in breast feeding behavior. More women were educated (secondary or higher, 35.9% vs. 21.2%), employed outside of the home (60.7% vs. 46.5%), and used contraceptives (34% vs. 20.8%) in 1986 than in 1977. Yet, mean duration of breast feeding and percent of ever breast fed children increased (14.3-17.1 months and 91.7-95.8%). The largest absolute significant increases occurred among women who, in 1977, were the least likely to breast feed and to breast feed for the shortest durations (urban women, highly educated women, professional women, and modern contraceptive users). These findings indicate that reductions in breast feeding incidence and duration are not necessarily inevitable as a society undergoes modernization. Between the two surveys, Peru's Ministry of Health had breast feeding promotion campaigns that stressed breast feeding during diarrheal episodes. They postulated that these campaigns were successful because the population already had adequate access to health care providers and to the mass media. Another possible factor contributing to the improvements in breast feeding patterns was the severe economic crisis in the early 1980s. Poor and uneducated women may have turned to breast milk as a substitute for other infant foods. These two possibilities raise some concerns. If the economy improves, the poor and uneducated may reduce breast feeding, but, if the breast feeding promotion campaigns indeed had the most impact, continuation of these campaigns would offset any declines and have a lasting impact on breast feeding behavior.

Effects of early-life conditions on adult mortality: a review.

"This paper considers the effects of health conditions in childhood on an individual's mortality risks as an adult. It examines epidemiologic evidence on some of the major mechanisms expected to create a linkage between childhood and adult mortality and reviews demographic and epidemiologic studies for evidence of the hypothesized linkages....Many empirical studies support the notion that childhood conditions play a major role in adult mortality, but only in the case of respiratory tuberculosis has the demographic importance of a specific mechanism been established by cohort studies. One's date and place of birth also appear to be persistently associated with risks of adult death in a wide variety of circumstances. An individual's height, perhaps the single best indicator of nutritional and disease environment in childhood, has recently been linked to adult mortality, especially from cardiovascular diseases. Further research is needed, however, before causal mechanisms can be identified."

Utilization of maternal health-care services in Peru: the role of women's education.

This article explores the hypothesis that formal education of women influences the use of maternal health-care services in Peru, net of the mother's childhood place of residence, household socioeconomic status and access to health-care services. The findings are consistent with the hypothesis; both cross-sectional and fixed-effects logit models yield quantitatively important and statistically reliable estimates of the positive effect of maternal schooling on the use of prenatal care and delivery assistance. In addition, large differentials were found in the utilization of maternal health-care services by place of residence, suggesting that much greater efforts on the part of the government are required if modern maternal health-care services are to reach women in rural areas.

PIP: The hypothesis that maternal education influences use of maternal health care services in Peru was analyzed by 4 logistic regression models, using data from the Peruvian Demographic and Health Survey of September-December 1986. Peru has one of the highest child-mortality rates in the region, with extreme variation across regions of the country, ranging from 34/1000 in Lima to 110/1000 in the Andean mountains. The conceptual framework for this study was the health-seeking model of Kroger who proposed that utilization depends on predisposing factors including education, characteristics of the illness, and of the health-care system. This study analyzed 1925 births, the last births to 4999 ever-married women in the 5 years before the survey. The 2 dependent variables were sources of prenatal care and assistance at delivery. 60.1% of the women had formal prenatal care, and 54.9% had formal delivery assistance for their last birth. The bivariate effects of maternal schooling were strongly associated with use of health care, with relative odds of 47.47 for delivery assistance, and 25.37 for prenatal care. Controlling for the woman's childhood background in Model 2 reduced the odds to 13.6 and 19.69, respectively. In model 3 access to care reduced relative odds to 8.33 for prenatal care and 10.70 for delivery assistance. Taking into account the household socioeconomic status in Model 4 reduced significance of the results. The results indicated that maternal education has a profound effect on seeking medical care, but in Peru the lack of access to care in the outlying rural areas supersedes maternal education.