BACKGROUND: Although stroke rates are much higher in old age, recent data on geographic variation in stroke incidence in older American populations were rare. Moreover, geographic variation in stroke incidence and mortality remain unexplained in United States. OBJECTIVES: To compare stroke incidence rates and stroke risk factors and their control in four US communities METHODS: Participants in the Cardiovascular Health Study (CHS) who had no history of stroke at baseline (n=5639) were followed for 10 years for the development of stroke events. Site specific stroke incidence and mortality rates were calculated. Possible risk factors at baseline and their control across the visits were compared among the four CHS sites. RESULTS: Age and sex standardized total stroke incidence rates per 1000 person-years were 9.6 (CI 7.7, 11.5) in Allegheny, 19.2 (CI 15.6, 22.8) in Forsyth, 20.7 (CI 16.9, 24.5) in Sacramento, and 19.8 (CI 16.1, 23.5) in Washington Counties. Although Allegheny County had the lowest stroke incidence among the 4 sites, risk factor distributions at baseline were similar. After adjustment for age, hypertension, diabetes, education, BMI, LDL cholesterol and previous coronary heart disease, transient ischemic attack (TIA), and atrial fibrillation (AF), there was modest reduction of the excess hazard in the other 3 sites compared to Allegheny County (HR=1.52, CI 1.17, 1.98 compared to 1.74 CI 1.42, 2.14). Moreover, between baseline and year 9, control of hypertension, diabetes, lipids, smoking, AF, and TIA were similar across sites. White matter grade (WMG) 3 or more on the baseline brain MRI was less common in Allegheny County than the other 3 sites (25.8%and 36.3% respectively, p< 0.001) and accounted for 25% of the excess hazard in the other 3 sites compared to Allegheny County (HR=1.65, CI 1.20-2.26 compared to 1.87 CI 1.36-2.55) CONCLUSION: Site-differences in stroke risk factors at baseline and their subsequent control only partially explain site-differences in stroke incidence. PUBLIC HEALTH SIGNIFICANCE: White matter grade may be a marker of integrated exposure and control of stroke risk factors and its progression could be used as a marker of the efficacy of different stroke prevention strategies on a community level.

Community integration for individuals diagnosed with schizophrenia is essential to successful community tenure. Most of the research and clinical emphasis on the process of integration has been focused on the successes in normative goals (e.g. employment, support networks). Little research has focused on how individuals diagnosed with schizophrenia integrate in the realm of public life involving the casual routine interactions with other community members, termed distal support in this study. This was a cross-sectional study specifically designed to develop a measure of distal support and to identify clinical and sociodemographic factors associated with fostering distal supports. Findings suggest that personality factors, particularly extraversion and openness, play a role in the process of fostering community distal supports while a higher functional status and lower symptom severity were found to have moderate associations. It was also found that a greater number of distal supports were associated with higher quality of life satisfaction ratings and sense of belonging scores. Contrary to the stated hypothesis, a greater number of distal supports were associated with a higher number of mental health contacts. This may be due, in part, to the confounding effects of the personality factors of extraversion and openness; both associated with a higher number of distal supports and with a greater willingness to seek support and to accept treatment during times of need. A greater understanding of what factors lead to successful community integration in this population has significant public health implications both in terms of improved quality of life and treatment interventions.

Background: Cryptorchidism is a failure of the testis to descend into the scrotum from its initial site of development in the abdomen. The failure of the testis to descend results in significant histologic changes to the testicular tissues and increases risk for infertility and testicular cancer. Incidence of cryptorchidism is approximately 3% at birth declining to 1% at one year of age because of spontaneous descent. Little to no spontaneous descent occurs after six months of age and surgical correction by orchiopexy is recommended by age one to two. Study Cohort: The Childrens Hospital of Pittsburgh Male Fertility Study has been looking at the impact of cryptorchidism on male fertility since 1992. The study cohort comprises 1405 former cryptorchids and control men. Each of the subjects completed an extensive questionnaire that included questions on marriage and cohabitation, paternity, health problems, and environmental/occupational exposures. A subset of the full cohort returned in adulthood for evaluation of hormone levels and semen analysis (n=167). Results: The articles presented here represent a selection of the study results looking at time to conception among formerly cryptorchid men, the impact of testicular suture on fertility, and the influence of age at orchiopexy on hormone levels and sperm count. Time to conception is significantly increased among formerly bilateral (33.9 months), but not unilateral cryptorchid men (11.1 months) as compared to control men (8.8 months). Placement of a transparenchymal suture during orchiopexy greatly increases the risk of infertility (RR 7.56) among formerly cryptorchid men. Age at orchiopexy is significantly negatively correlated (r= -0.274) with inhibin B and positively correlated (r=0.229) with FSH. Conclusions: Cryptorchidism negatively impacts fertility in the human male. It can increase time to conception and reduce sperm counts, especially among formerly bilateral cryptorchid men. Surgical technique utilizing placement of a suture through the testis can greatly increase risk for future infertility and should be avoided. With an incidence of 3% at birth and a prevalence of 1% at one year, it represents the single most common birth defect among human males. Cryptorchidism is of public health importance because it leads to significantly increased risks for both testicular cancer and infertility. Future research should focus on identifying environmental and behavioral causes of cryptorchidism and on optimizing treatment.

Despite higher prevalence of risk factors for coronary heart disease, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than Caucasians. In part, this is thought to be due to the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower levels of triglycerides and higher levels of HDL-C. The aim of the present study was to investigate the genetic contribution of two candidate genes, endothelial lipase (LIPG) and hepatic lipase (LIPC), to the ethnic variation in nuclear magnetic resonance (NMR) measured lipoproteins in 600 Caucasian, 100 African-American and 205 Tobago African-Caribbean men, older than 65 years. First, using a set of six ancestry informative markers, we estimated high African genetic contribution in the Tobago population (94%). A more favorable lipoprotein profile was observed in men of African origin compared to Caucasians. The frequency of the LIPG 584T allele in Tobago men (0.06) was five times less common than in Caucasians (0.29) and two times less common than in African-Americans (0.14). In African-Caribbeans, 584T allele was associated with lower small HDL and a greater HDL size, whereas in Caucasians and African-Americans, no significant association was found. Although, the LIPG 584T allele is protective in African-Caribbean men, its frequency is too low to explain the more favorable lipoprotein profile observed in these men. In contrast, the frequency of the LIPC -514T allele (0.57) was somewhat higher than the frequency in African-Americans (0.49), and three times as high as the frequency in Caucasians (0.20). 514C>T interacted with ethnicity to affect the levels of HDL-C, large HDL and HDL and LDL size. Carriers of 514T allele in both populations of African origin, but not in Caucasians, had elevated large HDL and greater HDL size. The higher frequency of the LIPC -514T allele in men of African origin significantly contributes to the more favorable distribution of HDL subclasses compared with Caucasians. Our findings have important public health relevance as they increase our understanding of Black-White differences in lipoprotein distributions, and are likely to increase our understanding of the underlying causes behind the ethnic differences in susceptibility to atherosclerosis.

BACKGROUND Atherosclerosis, endothelial dysfunction and inflammation are thought to be key pathophysiologic processes in preeclampsia. The basic thesis of this dissertation is that maternal infections may trigger upregulation of proinflammatory cytokines in women with preeclampsia resulting in vascular injury. OBJECTIVES We evaluated the evidence for a potential infectious disease etiology for preeclampsia in three papers. METHODS For the first paper, we conducted a 1:3 matched case control study. In this study we measured immunoglobulin G (IgG) antibodies to HSV-1, HSV-2, CMV, and EBV in serum samples obtained from 50 cases with preeclampsia and 150 normotensive controls, matched on age, parity and race. For the second paper, we conducted a comprehensive review of published studies that explored the association between both bacterial and viral infections, and examined the strength of this association. For the third paper, we investigated the association between self-reported Genital Warts (HPV), Genital Herpes (HSV-2), Chlamydia (C. trachomatis), Gonorrhea (N. gonorrhoeae) infections, sociodemographic, and behavioral risk factors and the risk of preeclampsia in a representative national sample of 10,847 reproductive age women. RESULTS We found that seroconversion for HSV 1 /2 or CMV was associated with a five-fold increased risk for developing preeclampsia (OR 5.4, 95% CI 1.0-29.0) after adjusting for education, income, smoking, years of cohabitation, medical insurance, and type of birth control. Pooling of relevant epidemiologic data, also revealed a two-fold increased risk of preeclampsia associated with bacterial and viral infections (OR 2.1, 95% CI 1.8-2.6). Additionally, population-based results suggest that Genital Warts, Genital Herpes, and C. trachomatis significantly increased the risk of preeclampsia (OR 3.0, 95% CI 1.0-8.8; OR 7.4, 95% CI 1.4-47.4; OR 5.2, 95% CI 1.3-20.2, respectively), after adjusting for socio-demographic, behavioral, and infection-related risk factors. PUBLIC HEALTH RELEVANCE Given the widespread prevalence of these infections, and the potential to prevent infection, our findings have important public health implications in the context of potential preventive strategies and identification of high-risk individuals.

Mothers who deliver a low birth weight infant may themselves be at excess risk for cardiovascular disease. We validated maternal recall of infant birth weight after an average follow up of 57 years, and investigated whether older women who reported having delivered low birth weight (LBW) infants (<2500 g) had later elevations in cardiovascular risk factors and were at increased risk for clinical cardiovascular disease. Participants were 446 women (mean age 80 years; 47% black) enrolled in The Health, Aging and Body Composition Study. Women reported birth weight and selected complications for each pregnancy, and pregnancies complicated by hypertension or preeclampsia were excluded. We found strong correlation between recalled and documented birth weights for first births (ICC=0.96) in a randomly selected group of participants, and reliability of recall for first births remained high when considered separately by race, education, income and age. Women who had reported a LBW first birth had a lower current BMI (adjusted for race and age) compared to women with normal weight infants (26.6 vs. 28.0 kg/m²; p=0.057), but they had a higher abdominal circumference (98.1 vs. 95.0 cm; p=0.007). After adjustment for BMI, race and age, women with a history of a LBW vs. normal weight infant had elevated systolic blood pressures (p=0.048) despite higher use of anti-hypertensive medication (p=0.061). Women with LBW infants also had higher levels of IL-6 (p=0.021), fasting insulin (p=0.064), and triglycerides (p=0.071), and they were more insulin resistant (p=0.045) compared to women with a normal weight infant. Women who delivered preterm infants had an elevated risk for cardiovascular disease at age 80 (adjusted odds ratio=2.77, 95% CI 1.06-7.24) compared to women who delivered term infants. Women who had delivered infants both LBW and preterm had markedly elevated cardiovascular risk factors when compared to women with normal weight term infants, and appeared to have the highest risk for clinical cardiovascular disease (adjusted odds ratio=4.21, 95% CI 1.23-14.45). The public health importance of these findings is that a history of LBW or preterm delivery may identify women who would benefit from screening and intervention aimed at risk factors for cardiovascular disease.

This dissertation demonstrates the versatility of epidemiology in public health research. The association between hearing sensitivity and diabetes, cardiovascular disease (CVD), and their risk factors was examined in a population of 2,049 adults within the Health, Aging, and Body Composition Study (mean age 77.5 ± 2.8 years; 37% black). CVD and diabetes may contribute to age-related hearing loss by affecting blood flow within the inner ear via macro- and micro-vascular changes. Clinical CVD was not associated with hearing sensitivity however; subclinical CVD measures were moderately associated with poorer auditory function in females. After controlling for age, race, and site, CVD risk factors positively associated with worse mid-frequency hearing thresholds in males were weight, insulin, glucose, triglycerides, and smoking and in females were heart rate and glucose. Risk factors associated with worse high frequency thresholds were weight, insulin, triglycerides, and smoking in males and heart rate, glucose, and smoking in females. Diabetes was associated with mid-frequency hearing loss upon adjustment for common hearing loss risk factors (OR=1.60; 95%CI: 1.262.02). The metabolic syndrome was associated with mid-frequency hearing loss in whites prior to excluding diabetics. These results suggest that diabetes, in conjunction with CVD, contributes to age-related hearing loss, particularly strial presbycusis, and independent of common hearing loss risk factors. Given the high prevalence of hearing impairment among older adults, the identification of potentially modifiable risk factors for age-related hearing loss is of public health significance. Epidemiology can also be utilized in more applied settings. A retrospective cohort study was conducted to determine if residents affected by an underground gasoline spill in Hazle Township/Hazleton, Pennsylvania were at increased risk for cancer from 1990-2000. A total of 663 individuals representing 275 households comprised the study population. Age-adjusted standard incidence ratios (SIRs) were calculated using Pennsylvania rates to determine expected numbers. The age-adjusted leukemia SIR for the gasoline affected area was 4.40 (95%CI: 1.09-10.24). These results suggest a possible association between chronic low-level benzene exposure and increased risk for leukemia in the residents living near the spill site. This project directly impacted the public health of residents and also demonstrated the importance of collaboration and surveillance.

Systemic lupus erythematosus (SLE) affects a significant portion of young women of childbearing age worldwide, in particular those of non-white descent. In the United States, the incidence ranges 8.1-11.4 per 100,000 among African-American, and 2.5-3.9 per 100,000 among Caucasian women. The prevalence is estimated 56-283 per 100,000 among African-American, and 17-71 per 100,000 among Caucasian women. Understanding the natural history of systemic lupus, its major complications such as cardiovascular disease and associated risk factors, identifying major biomarkers for timely and accurate diagnosis of the disease itself and its manifestations is of great public health importance, since this will help to reduce morbidity and mortality among lupus patients. The dissertation consists of three relevant chapters. The first chapter is an overview of candidate biomarkers for diagnosis of SLE. It includes a brief review of the role of complement molecules in SLE pathogenesis, evaluation of the past and current uses of complement in monitoring SLE disease activity, and summary of recent findings that propose a novel method of measuring complement activation to specifically and sensitively diagnose SLE. The chapter concludes by discussing how this method may also support the resurgence of complement as a valuable biomarker of SLE disease activity. The second chapter is the cost effectiveness analysis of the novel diagnostic biomarker discussed in chapter one. The analysis shows that using the novel diagnostic biomarker along with the traditional tests can be cost effective for the population of patients contemplating SLE. Chapter three is devoted to atherosclerosis as a major complication of SLE and to coronary calcification measured by electron beam tomography (EBT) as a major biomarker of subclinical atherosclerosis. The risk factors associated with subclinical vascular disease in women with SLE are also reported. It is concluded that atherosclerosis of the coronary arteries detected by EBT is highly prevalent in patients with SLE and is related to many potentially modifiable traditional, SLE-specific and inflammatory risk factors for vascular disease.

Finding high quality materials for the preparation of epidemiological lectures is a serious challenge for epidemiologists and public health professionals across the world. The emergence of the Internet in the early 90s offered a way to ease the access to the epidemiological lectures; however it also raised important questions about the quality of the educational lectures which are freely available on the Internet. In this research, we analyzed the quality of epidemiological lectures in the Global Health Network Supercourse lecture library. We selected a random sample of 100 lectures in the Supercourse that accumulated at least 3 reviews from the visitors of the Supercourse sites. We found 7 experts, leading researchers in the field of public health and medicine, who were also very experienced in reviewing papers for journals. These experts evaluated the same set of 100 lectures and gave us their expert opinion on their quality. Overall, the lectures were rated positively by both expert and the Supercourse reviewers. Although t-test indicated that the difference between the means was statistically significant, this difference is not meaningful due to large sample size. Kappa statistic and intraclass correlations indicated that inter rater agreement for experts and non-experts was surprisingly low (less than 0.4). We also observed HALO affect with overall score being a good predictor of other scores. Our findings were consistent with existing research in the area of peer review, demonstrating low inter rater agreement. This poor inter rater agreement was demonstrated for the first time for the Internet lectures. Our findings suggested that questionnaires assessing the quality of the Internet lectures may actually be replaced by one rating, similar to the system utilized in Amazon.com or hotel ratings. This research was significant for the field of public health because it was one of the first efforts to evaluate the quality of epidemiological lectures on the Internet. The quality of lectures on the web has rarely been assessed scientifically for epidemiological and public health lectures. Future research in this area may need to concentrate on alternatives to the peer review system.

Breast cancer is major cause of morbidity and mortality globally and the incidence appears to be rising faster in population groups that hitherto experience lower incidence. This case control study recruiting 250 women with breast cancer and 250 age-matched controls from four University Teaching Hospitals in Nigeria was designed to evaluate the risk factors for breast cancer in Nigerian women. Family history of breast cancer was associated with a 15-fold increased risk of breast cancer [Odd ratio (OR) = 14.99, 95% Confidence interval (CI), 1.98, 113.47]. Also, waist to hip ratio (OR = 2.10, 95% CI 1.44, 3.06), history of abortion (OR = 2.83, 95% CI 1.12, 7.19), increasing age at first childbirth (OR = 1.39 95% CI 1.11, 1.73) and higher level of education (OR = 1.31, 95% CI 1.07, 1.61) conferred increased risk of breast cancer. Increasing parity (OR = 0.87, 95% CI 0.77, 0.99) and increasing duration of breastfeeding (OR = 0.75, 95% CI 0.62, 0.91) conferred protection against breast cancer. In the final multivariate conditional logistic regression in all women, carrying at least one low-activity COMT (Met) allele was associated with a significant 43% reduced risk of breast cancer (OR = 0.57, 95% CI 0.36-0.91). While harboring the CYP1A1 M1 polymorphic variant was associated with non-significant reduced risk of breast cancer (OR = 0.79, 95% CI 0.48-1.29), the CYP1A1 M3 polymorphism conferred a non-significant 24% reduced risk of breast cancer (OR = 0.76, 95% CI 0.47-1.22). Results of this study have important public health implications; it has provided evidence for a role for reproductive and other variables in susceptibility to breast cancer in indigenous African women, thus contributing to the global epidemiologic literature on risk factors for breast cancer in populations of African ancestry. It has also provided data suggesting protection for breast cancer for women harboring the low-activity COMT (Met) allele of the codon 158 polymorphism of the COMT gene. In addition, the findings of this study will serve a useful resource tool in future research and policy decisions aimed at breast cancer control and prevention in these populations.