Gender differences in colorectal cancer screening and incidence in large nationwide, population-based cohorts

Background. A few studies have reported gender differences along the colorectal cancer (CRC) continuum but none has done so longitudinally to compare a cancer and a non-cancer populations.^ Objectives and Methods. To examine gender differences in colorectal cancer screening (CRCS); to examine trends in gender differences in CRC screening among two groups of patients (Medicare beneficiaries with and without cancer); to examine gender differences in CRC incidence; and to examine for any differences over time. In Paper 1, the study population consisted of men and women, ages 67–89 years, with CRC (73,666) or without any cancer (39,006), residing in 12 U.S. Surveillance Epidemiology and End-Results (SEER) regions. Crude and age-adjusted percentages and odds ratios of receiving fecal occult blood test (FOBT), sigmoidoscopy (SIG), or colonoscopy (COL) were calculated. Multivariable logistic regression was used to assess gender on the odds of receiving CRC screening over time.^ In Paper 2, age-adjusted incidence rates and proportions over time were reported across race, CRC subsite, CRC stage and SEER region for 373,956 patients, ages 40+ years, residing in 9 SEER regions and diagnosed with malignant CRC. ^ Results. Overall, women had higher CRC screening rates than men and screening rates in general were higher in the SEER sample of persons with CRC diagnosis. Significant temporal divergence in FOBT screening was observed between men and women in both cohorts. Although the largest temporal increases in screening rates were found for COL, especially among the cohort with CRC, little change in the gender gap was observed over time. Receipt of FOBT was significantly associated with female gender especially in the period of full Medicare coverage. Receipt of COL was also significantly associated with male gender, especially in the period of limited Medicare coverage.^ Overall, approximately equal numbers of men (187,973) and women (185,983) were diagnosed with malignant CRC. Men had significantly higher age-adjusted CRC incidence rates than women across all categories of age, race, subsite, stage and SEER region even though rates declined in all categories over time. Significant moderate increases in rate difference occurred among 40-59 year olds; significant reductions occurred among patients age 70+, within subsite rectum, unstaged and distant stage CRC, and eastern and western SEER regions. ^ Conclusions. Persistent gender differences in CRC incidence across time may have implications for gender-based interventions that take age into consideration. A shift toward proximal cancer was observed over time for both genders, but the high proportion of men who develop rectal cancer suggests that a greater proportion of men may need to be targeted with newer screening methods such as fecal DNA or COL. Although previous reports have documented higher CRC screening among men, higher incidence of CRC observed among men suggests that higher risk categories of men are probably not being reached. FOBT utilization rates among women have increased over time and the gender gap has widened between 1998 and 2005. COL utilization is associated with male gender but the differences over time are small.^

Early life risk factors and puberty implications for cancer prevention

Earlier age at puberty is a known risk factor for breast cancer and suspected to influence prostate cancer; yet few studies have assessed early life risk factors for puberty. The overall objectives was to determine the relationship between birth-weight-for-gestational-age (BWGA), weight gain in infancy and pubertal status in girls and boys at 10.8 and 11.8 years and who were born of preeclamptic (PE) and normotensive (NT) mothers. Data for this study were collected from hospital and public health medical records and at a follow-up visit at 10.8 and 11.8 years for girls and boys, respectively. We used stratified analysis and multivariable logistic regression modeling to assess effect measure modifier and to determine the relationship between BWGA, weight gain in infancy and childhood and pubertal status, respectively. ^ There was no difference in the relationship between BWGA and pubertal status by maternal PE status for girls and boys; however, there was a non-significant increase in the odds of having been born small-for-gestational-age (SGA) in girls who were pubertal for breast or pubic hair Tanner stage 2+ compared to those who B1 or PH1. In contrast, boys who were pubertal for genital and pubic hair Tanner stage 2+ had lower odds of having been born SGA than those who were prepubertal for G1 or PH1. ^ In girls who were pubertal for breast development, the odds of having gained one additional unit SD for weight was highest between 3 to 6 months and 6-12 months for those who were B2+ vs. B1. For pubic hair development, weight gain between 6-12 months had the greatest effect for girls of PE mothers only. In boys, there were no statistically significant associations between weight gain and genital Tanner stage at any of the intervals; however, weight gain between 3-6 months did affect pubic hair tanner stage in boys of NT mothers. This study provide important evidence regarding the role of SGA and weight gain at specific age intervals on puberty; however, larger studies need to shed light on modifiable exposures for behavioral interventions in pregnancy, postpartum and in childhood.^

Pregnancy intention, intimate partner violence, and the use of prenatal care in Jordan

Previous research has suggested an association between intimate partner violence and pregnancy intention status, and pregnancy intention status and the use of prenatal care services, however much of these studies have been conducted in high income countries (HIC) rather than low and middle income countries (LMIC). The objectives of this study were to examine the relationship between pregnancy intention status and intimate partner violence, and pregnancy intention status and the use of prenatal care among ever-married women in Jordan.^ Data were collected from a nationally representative sample of women interviewed in the 2007 Jordan Demographic and Health Survey. The sample was restricted to ever-married women, 15–49 years of age, who had a live birth within the five years preceding the survey. Multivariate logistic regression analyses was used to determine the relationship between intimate partner violence and pregnancy intention status, and pregnancy intention status and the use of prenatal care services.^ Women who reported a mistimed pregnancy (PORadj 1.96, 95% CI: 1.31–2.95), as well as an unwanted pregnancy (PORadj 1.32, 95% CI: 0.80–2.18) had a higher odds of experiencing lifetime physical and/or sexual abuse compared with women reporting a wanted pregnancy. Women not initiating prenatal care by the end of the first trimester had statistically significant higher odds of reporting both a mistimed (PORadj 2.07, 95% CI: 1.55–2.77) and unwanted pregnancy (PORadj 2.36, 95% CI: 1.68–3.31), compared with women initiating care in the first trimester. Additionally, women not receiving the adequate number of prenatal care visits for their last pregnancy had a higher odds of reporting an unwanted pregnancy (PORadj 2.11, 95% CI: 1.35–3.29) and mistimed pregnancy (POR adj 1.41, 95% CI: 0.96–2.07).^ Reducing intimate partner violence may decrease the prevalence of mistimed or unwanted pregnancies, and reducing both unwanted and mistimed pregnancies may decrease the prevalence of women not receiving timely and adequate prenatal care among women in this population. Further research, particularly in LMIC, is needed regarding the determinants of unintended pregnancy and its association with intimate partner violence as well as with the use of prenatal care services. ^

Metabolic syndrome and cardiovascular mortality among participants of the hypertension detection and follow-up program

Metabolic Syndrome (MetS) is a clustering of cardiovascular (CV) risk factors that includes obesity, dyslipidemia, hyperglycemia, and elevated blood pressure. Applying the criteria for MetS can serve as a clinically feasible tool for identifying patients at high risk for CV morbidity and mortality, particularly those who do not fall into traditional risk categories. The objective of this study was to examine the association between MetS and CV mortality among 10,940 American hypertensive adults, ages 30-69 years, participating in a large randomized controlled trial of hypertension treatment (HDFP 1973-1983). MetS was defined as the presence of hypertension and at least two of the following risk factors: obesity, dyslipidemia, or hyperglycemia. Of the 10,763 individuals with sufficient data available for analysis, 33.2% met criteria for MetS at baseline. The baseline prevalence of MetS was significantly higher among women (46%) than men (22%) and among non-blacks (37%) versus blacks (30%). All-cause and CV mortality was assessed for 10,763 individuals. Over a median follow-up of 7.8 years, 1,425 deaths were observed. Approximately 53% of these deaths were attributed to CV causes. Compared to individuals without MetS at baseline, those with MetS had higher rates of all-cause mortality (14.5% v. 12.6%) and CV mortality (8.2% versus 6.4%). The unadjusted risk of CV mortality among those with MetS was 1.31 (95% confidence interval [CI], 1.12-1.52) times that for those without MetS at baseline. After multiple adjustment for traditional risk factors of age, race, gender, history of cardiovascular disease (CVD), and smoking status, individuals with MetS, compared to those without MetS, were 1.42 (95% CI, 1.20-1.67) times more likely to die of CV causes. Of the individual components of MetS, hyperglycemia/diabetes conferred the strongest risk of CV mortality (OR 1.73; 95% CI, 1.39-2.15). Results of the present study suggest MetS defined as the presence of hypertension and 2 additional cardiometabolic risk factors (obesity, dyslipidemia, or hyperglycemia/diabetes) can be used with some success to predict CV mortality in middle-aged hypertensive adults. Ongoing and future prospective studies are vital to examine the association between MetS and cardiovascular morbidity and mortality in select high-risk subpopulations, and to continue evaluating the public health impact of aggressive, targeted screening, prevention, and treatment efforts to prevent future cardiovascular disability and death.^

Is depression associated with insulin resistance? A systematic review

Studies suggest that depression affects glucose metabolism, and therefore is a risk factor for insulin resistance. The association between depression and insulin resistance has been investigated in a number of studies, but there is no agreement on the results. The objective of this study is to survey the epidemiological studies, identify the ones that measured the association of depression (as exposure) with insulin resistance (as outcome), and perform a systematic review to assess the reliability and strength of the association. For high quality reporting, and assessment, this systematic review used the outlined procedures, guidelines and recommendations for reviews in health care, suggested by the Centre for Reviews and Dissemination, along with recommendations from the STROBE group (Strengthening the Reporting of Observational Studies in Epidemiology). Ovid MEDLINE 1996 to April Week 1 2010, was used to identify the relevant epidemiological studies. To identify the most relevant set of articles for this systematic review, a set of inclusion and exclusion criteria were applied. Six studies that met the specific criteria were selected. Key information from identified studies was tabulated, and the methodological quality, internal and external validity, and the strength of the evidence of the selected studies were assessed. The result from the tabulated data of the reviewed studies indicates that the studies either did not apply a case definition for insulin resistance in their investigation, or did not state a specific value for the index used to define insulin resistance. The quality assessment of the reviewed studies indicates that to assess the association between insulin resistance and depression, specifying a case definition for insulin resistance is important. The case definition for insulin resistance is defined by the World Health Organization and the European Group for the Study of Insulin Resistance as the insulin sensitivity index of the lowest quartile or lowest decile of a general population, respectively. Three studies defined the percentile cut-off point for insulin resistance, but did not give the insulin sensitivity index value. In these cases, it is not possible to compare the results. Three other studies did not define the cut-off point for insulin resistance. In these cases, it is hard to confirm the existence of insulin resistance. In conclusion, to convincingly answer our question, future studies need to adopt a clear case definition, define a percentile cut-off point and reference population, and give value of the insulin resistance measure at the specified percentile.^

Shigellosis in Hidalgo County, Texas 2005--2009: A descriptive study

Shigellosis is a communicable disease harbored primarily by humans. The low infective dose, no vaccine availability, and mild or asymptomatic nature of disease has prevented eradication of Shigella in the United States. In addition, the lack of water and sewage infrastructures which normally contribute to the spread of disease in developing countries, for the most part, is a non-issue in the U.S. making surveillance and risk factor identification important prevention and control measures utilized to reduce the incidence rates of Shigellosis.^ The purpose of this study was to describe the Shigellosis disease burden among the Hidalgo County, Texas population during the 2005-2009 study period and compare these findings with national data available. The potential identification and publication of a health disparity in the form of increased Shigellosis rates among Hidalgo County residents when compared to national rates, especially age-specific rates, are intended to generate public health attention and public health action that will address this issue.^ There were 1,007 confirmed Shigellosis cases reported in Hidalgo County, Texas. An overwhelming majority (79%) of the Shigellosis cases during this time frame occurred in children less than ten years of age. Over the age of 10 through the age of 39, females constituted the majority of cases. Age-specific rates for children four years of age and younger were compared to national rates. The rates for Hidalgo County were higher at 9.2 and 1.8 cases for every one case reported nationally in 2005 and 2006, respectively. The total crude rates of Shigellosis were also higher than the rates available from the Foodborne Diseases Active Surveillance Network (FoodNet) of CDC’s Emerging Infections Program from 2005-2009. As a result, compared to the FoodNet surveillance rates, Hidalgo County experienced above average rates of Shigellosis throughout the study period. The majority of cases were identified in young children under the age of ten.^ The information gathered in this analysis could be used to implement and monitor infection control measures such as hand washing education at facilities that tend to the groups identified at higher risk of infection. In addition, the higher burden of disease found in Hidalgo County requires further study to determine if there are factors associated with an increased risk of Shigellosis in this community and other border communities along the U.S.-Mexico border exist.^

Effect of the emergence of community acquired methicillin resistant Staphylococcus aureus on microbial resistance patterns seen during a seven year study of minocycline/rifampin catheter use

Background. Health care associated catheter related blood stream infections (CRBSI) represent a significant public health concern in the United States. Several studies have suggested that precautions such as maximum sterile barrier and use of antimicrobial catheters are efficacious at reducing CRBSI, but there is concern within the medical community that the prolonged use of antimicrobial catheters may be associated with increased bacterial resistance. Clinical studies have been done showing no association and a significant decrease in microbial resistance with prolonged minocycline/rifampin (M/R) catheter use. One explanation is the emergence of community acquired methicillin resistant Staphylococcus aureus (MRSA), which is more susceptible to antibiotics, as a cause of CRBSI.^ Methods. Data from 323 MRSA isolates cultured from cancer patients at The University of Texas MD Anderson Cancer center from 1997-2007 displaying MRSA infection were analyzed to determine whether there is a relationship between resistance to minocycline and rifampin and prolonged wide spread use of minocycline (M/R) catheters. Analysis was also conducted to determine whether there was a significant change in the prevalence community acquired MRSA (CA-MRSA) during this time period and if this emergence act as a confounder masquerading the true relationship between microbial resistance and prolonged M/R catheter use.^ Results. Our study showed that the significant (p=0.008) change in strain type over time is a confounding variable; the adjusted model showed a significant protective effect (OR 0.000281, 95% CI 1.4x10 -4-5.5x10-4) in the relationship between MRSA resistance to minocycline and prolonged M/R catheter use. The relationship between resistance to rifampin and prolonged M/R catheter use was not significant.^ Conclusion. The emergence of CA-MRSA is a confounder and in the relationship between resistance to minocycline and rifampin and prolonged M/R catheter use. However, despite the adjustment for the more susceptible CA-MRSA the widespread use of M/R catheters does not promote microbial resistance. ^

Epidemiological trends of influenza A positive patients hospitalized at St. Luke's Episcopal Hospital, Houston, Texas September, 2009--January, 2010

This study was a descriptive analysis of 437 influenza A positive inpatients and outpatients during the five month period between September, 2009 and January, 2010. The objective of the study was to describe the epidemiological trends of the total influenza A positive population and more specifically the clinical features of patients hospitalized with influenza A at St. Luke's Episcopal Hospital in Houston, Texas from September 2009 through January 2010. Eligible cases were included if they tested positive for influenza A test using the rapid antigen test and/or rRT-PCR. Hospitalized cases were included based on the laboratory confirmation of influenza A as well as hospital admission for at least 24 hours. Data was collected from medical record abstraction and included patient demographics, clinical history and history of chronic disease. Clinical findings in the differential diagnosis that led to laboratory-confirmation of influenza A as well as course of treatment during the hospital admission were summarized. Finally, co-morbid conditions charted during the hospital visit were reviewed and evaluated for associations with influenza A complications. During the study period, forty-eight patients were included in the study of which 27 tested positive for the H1N1 subtype. Females were more likely to be hospitalized than men. The median age of all patients admitted to St. Luke's Episcopal Hospital with influenza A was 42. The distribution for admitted cases was 15 White, 15 Black, and 18 Hispanic. Patients with co-morbid disease constituted 81% of the admissions for Influenza A. The presence of an underlying medical condition remains a risk factor for both seasonal and H1N1 influenza. Although respiratory conditions such as asthma and COPD are commonly associated with complications of seasonal influenza, patients with metabolic disorders such as kidney disease and/or diabetes were admitted more frequently (58%) during the study period. The patients in the study also of a much younger age than the age that is usually associated with complications of influenza infection, i.e. no patients greater than 65 years of age were admitted with a diagnosis of influenza A. Lower infection rates among elderly populations were similarly reported in other studies of influenza during the same time period. Older patient populations may benefit from antibodies to previous H1N1 strains that have circulated during the twentieth century, whereas younger age groups lack these exposures.^

Physical activity among breast and prostate cancer survivors: Barriers, facilitators and maintenance following the FRESH START trial

Research provides evidence of the positive health effects associated with regular physical activity participation in all populations. Activity may prove to be especially beneficial in those with chronic conditions such as cancer. However, the majority of cancer patients and survivors do not participate in the recommended amount of physical activity. The purpose of this dissertation was to identify factors associated with physical activity participation, describe how these factors change as result of a diet and exercise intervention, and to evaluate correlates of long term physical activity maintenance. ^ For this dissertation, I analyzed data from the FRESH START trial, a randomized, single-blind, phase II clinical trial focused on improving diet and physical activity among recently diagnosed breast and prostate cancer survivors. Analyses included both parametric and non-parametric statistical tests. Three separate studies were conducted, with sample sizes ranging from 400 to 486. ^ Common barriers to exercise, such as “no willpower,” “too busy,” and “I have pain,” were reported among breast and prostate cancer survivors; however, these barriers were not significantly associated with minutes of physical activity. Breast cancer survivors reported a greater number of total barriers to exercise as well as higher proportions reporting individual barriers, compared to prostate cancer survivors. Just less than half of participants reduced their total number of barriers to exercise from baseline to 1-year follow-up, and those who did reduce barriers reported greater increases in minutes of physical activity compared to those who reported no change in barriers to exercise. Participants in both the tailored and standardized intervention groups reported greater minutes of physical activity at 2-year follow-up compared to baseline. Overall, twelve percent of participants reached recommended levels of physical activity at both 1- and 2-year follow-up. Self-efficacy was positively associated with physical activity maintenance, and the number of total barriers to exercise was inversely associated with physical activity maintenance. ^ Results from this dissertation are novel and informative, and will help to guide future physical activity interventions among cancer survivors. Thoughtfully designed interventions may encourage greater participation in physical activity and ultimately improve overall quality of life in this population. ^

HPV vaccine coverage in Texas counties: An application of multilevel, small area estimation

Health departments, research institutions, policy-makers, and healthcare providers are often interested in knowing the health status of their clients/constituents. Without the resources, financially or administratively, to go out into the community and conduct health assessments directly, these entities frequently rely on data from population-based surveys to supply the information they need. Unfortunately, these surveys are ill-equipped for the job due to sample size and privacy concerns. Small area estimation (SAE) techniques have excellent potential in such circumstances, but have been underutilized in public health due to lack of awareness and confidence in applying its methods. The goal of this research is to make model-based SAE accessible to a broad readership using clear, example-based learning. Specifically, we applied the principles of multilevel, unit-level SAE to describe the geographic distribution of HPV vaccine coverage among females aged 11-26 in Texas.^ Multilevel (3 level: individual, county, public health region) random-intercept logit models of HPV vaccination (receipt of ≥ 1 dose Gardasil® ) were fit to data from the 2008 Behavioral Risk Factor Surveillance System (outcome and level 1 covariates) and a number of secondary sources (group-level covariates). Sampling weights were scaled (level 1) or constructed (levels 2 & 3), and incorporated at every level. Using the regression coefficients (and standard errors) from the final models, I simulated 10,000 datasets for each regression coefficient from the normal distribution and applied them to the logit model to estimate HPV vaccine coverage in each county and respective demographic subgroup. For simplicity, I only provide coverage estimates (and 95% confidence intervals) for counties.^ County-level coverage among females aged 11-17 varied from 6.8-29.0%. For females aged 18-26, coverage varied from 1.9%-23.8%. Aggregated to the state level, these values translate to indirect state estimates of 15.5% and 11.4%, respectively; both of which fall within the confidence intervals for the direct estimates of HPV vaccine coverage in Texas (Females 11-17: 17.7%, 95% CI: 13.6, 21.9; Females 18-26: 12.0%, 95% CI: 6.2, 17.7).^ Small area estimation has great potential for informing policy, program development and evaluation, and the provision of health services. Harnessing the flexibility of multilevel, unit-level SAE to estimate HPV vaccine coverage among females aged 11-26 in Texas counties, I have provided (1) practical guidance on how to conceptualize and conduct modelbased SAE, (2) a robust framework that can be applied to other health outcomes or geographic levels of aggregation, and (3) HPV vaccine coverage data that may inform the development of health education programs, the provision of health services, the planning of additional research studies, and the creation of local health policies.^

The association of previous induced abortion with the subsequent pregnancy complication of placenta previa

Placenta previa is alleged to be more common among women with a history of prior induced abortion. To investigate further whether there is a relationship between previous induced abortion and subsequent pregnancy complication of placenta previa, a matched case-comparison study was conducted comparing the reproductive histories of 256 women with placenta previa matched on age, date of delivery, and hospital with those of 256 women having normal deliveries and cesarean section deliveries without placental complications.^ Women with placenta previa had a twofold increase in the odds of having had one previous induced abortion (odds ratio 2.25) over women with no placental complications. Women with placenta previa and two or more previous induced abortions had a sevenfold increase in odds.^ The significant association of placenta previa and previous induced abortion remained after including gravida status, previous dilatation and curettage (D&C) status, previous spontaneous abortion, and race in a conditional logistic regression model. There is interaction between high gravidity and previous spontaneous abortion. Dilatation and curettage is associated with placenta previa primarily because women with abortion histories have also had a dilatation and curettage.^ Women who are seeking abortion and wish to have children later should be informed that there may be a longterm effect of developing placental complications in subsequent pregnancies. Women who have had at least one induced abortion or any dilatation and curettage procedure should be monitored carefully during any subsequent pregnancy for the risk of the complication of placenta previa. This knowledge should alert the physician or nurse-midwife to treat those women with a history of previous induced abortions as potential high risk pregnancies and could perhaps reduce maternal and fetal morbidity rates. ^

Genetic epidemiology of childhood brain tumors

A rare familial cancer syndrome involving childhood brain tumors (CBT), breast cancer, sarcomas and an array of other tumors has been described (Li and Fraumeni 1969, 1975, 1982, 1987). A survey of CBT identified through the Connnecticut Tumor Registry in 1984 revealed a high frequency of CBT, leukemia and other childhood cancer in siblings of CBT patients (Farwell and Flannery, 1984). Other syndromes such as neurofibromatosis and nevoid basal cell carcinoma syndrome have also been associated with CBT; however, no systematic family studies have been conducted to determine the extent to which cancer aggregates in family members of CBT patients. This family study was designed to determine the frequency of cancer aggregation overall or at specific sites, to determine the frequency of known or potentially hereditary syndromes in families of CBT patients, and to determine a genetic model to characterize familial cancer syndromes and to identify specific kindreds to which such a model(s) might apply. This study includes 244 confirmed CBT patients referred to the University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed under the age of 15 years and resident in the U.S. or Canada. Family histories were obtained on the proband's first (parents, siblings and offspring) and second degree (proband's aunts, uncles and grandparents) relatives following sequential sampling scheme rules. To determine if cancer aggregates in families, we compared the cancer experience in the population to that expected in the general population using Connecticut Tumor Registry calendar year, age, race and sex-specific rates. The standardized incidence ratio (SIR) for cancer overall was 0.91 (41 observed (O) and 44.94 expected (E); 95% Confidence Interval (CI) = 0.65-1.24). We observed a significant excess of colon cancer among the proband's first degree relatives (O/E = 5/1.64; 95% CI = 1.01-7.65), in particular those under age 45 year. Segregation analysis showed evidence for multifactorial inheritance in the small percentage (N = 5) of the families. ^

The relationship between calcium and fluoride intake, pregnancy and lactation and the risk of height loss in white women

This study was designed to investigate the effect of calcium and fluoride intake, and parity and lactation on the risk of spinal osteoporosis. Height loss was used as a surrogate measure for spinal fractures by taking advantage of documented changes in height found during the 25-year follow-up of the Charleston Heart Study cohort. Women who had lost 2-4" in height or who had no change in height during the follow-up period were defined as case and comparison subjects respectively. Calcium intake when the subjects were "about 25" and in the recent past, average intake of fluoride over 25 years, and parity and history of breastfeeding were ascertained by questionnaire from 54 case and 77 comparison subjects. Low calcium intake in the past decreased the risk of height loss (age-adjusted OR = 0.3, 95%CI: 0.1-0.96) although several potentially important confounding variables could not be adjusted for. There was no association between risk of height loss and present calcium intake (OR = 0.8, 95%CI: 0.3-2.6 for low versus high intake) after adjustment for past calcium intake. High fluoride intake decreased the risk of height loss (adjusted OR = 0.4, 95%CI: 0.1-1.2). The effect of fluoride or calcium intake in the present was modified by the level of the other nutrient. Compared to a low intake of both calcium and fluoride, a high intake of one increased the risk of height loss (crude OR = 3.3 for high fluoride/low calcium, crude OR = 6.0 for high calcium/low fluoride) although a high intake of both was slightly protective (crude OR = 0.7). It is estimated that a "high" nutrient intake in this population was greater than 850mg/day for calcium and 2mg/day for fluoride. After adjustment for age, increasing parity decreased the risk of height loss in women who had never breastfed (OR = 0.2, 95%CI: 0.01-1.7 for 4 or more children). Women who had breastfed were also at lower risk of height loss than nulliparous women (OR = 0.3, 95%CI: 0.1-1.2 for 4 or more children) although at any level of parity, breastfeeding women had a greater risk of height loss than did non-breastfeeding women. ^

The social construction of infant mortality: From grassroots to medicalization

Infant mortality as a problematic situation has been recognized for some 130 years in one form or another. It has undergone various changes in its empirical dimensions relative to whom we study within the population, what we study--low birth-weight vs. pre-term births--and how we study it--whether demographically or medically. An analysis of the process by which the condition was raised by claims makers as an intolerable situation among America's urban residents reveals that demographic and medical data were sparse. Nonetheless, a judgement about the meaning and significance of the condition was made, and that interpretation led to the promulgation of systems to both document and address the condition as it has come to be defined.^ This investigation depicts the historical context and natural history of infant mortality as one of a number of social problems that came to be defined through the interplay among groups and individuals making claims and how their claims came to the public policy agenda as worthy of collective resources--who won, who lost and why. The process of social definition focuses attention on the claims makers and the ways they contrast the meaning, origins and remedies for this troubling condition. The historical context becomes the frame of reference for understanding the actions of the claims makers and the meaning and significance they attached to the problem.^ We purport that "context" provides a closer reality than disjoined "value free" accounts. Context provides the evidence for the definition, who participated in the process, why and by what means.^ The role of women in the definitional process reveals the differences in approaches utilized by the women of the settlement house reform movement and African-American women working at the grass-roots. Much of the work done by these two groups provided options to the problem's remedy; however, their differences paved the way to our current (principally medically-oriented) definition and its inherent limitations. ^

Genetic epidemiology of gallbladder disease in Mexican Americans and cholesterol 7$\alpha$-hydroxylase gene sequence variation

Among Mexican Americans, the second largest minority group in the United States, the prevalence of gallbladder disease is markedly elevated. Previous data from both genetic admixture and family studies indicate that there is a genetic component to the occurrence of gallbladder disease in Mexican Americans. However, prior to this thesis no formal genetic analysis of gallbladder disease had been carried out nor had any contributing genes been identified.^ The results of complex segregation analysis in a sample of 232 Mexican American pedigrees documented the existence of a major gene having two alleles with age- and gender-specific effects influencing the occurrence of gallbladder disease. The estimated frequency of the allele increasing susceptibility was 0.39. The lifetime probabilities that an individual will be affected by gallbladder disease were 1.0, 0.54, and 0.00 for females of genotypes "AA", "Aa", and "aa", respectively, and 0.68, 0.30, and 0.00 for males, respectively. This analysis provided the first conclusive evidence for the existence of a common single gene having a large effect on the occurrence of gallbladder disease.^ Human cholesterol 7$\alpha$-hydroxylase is the rate-limiting enzyme in bile acid synthesis. The results of an association study in both a random sample and a matched case/control sample showed that there is a significant association between cholesterol 7$\alpha$-hydroxylase gene variation and the occurrence of gallbladder disease in Mexican Americans males but not in females. These data have implicated a specific gene, 7$\alpha$-hydroxylase, in the etiology of gallbladder disease in this population.^ Finally, I asked whether the inferred major gene from complex segregation analysis is genetically linked to the cholesterol 7$\alpha$-hydroxylase gene. Three pedigrees predicted to be informative for linkage analysis by virtue of supporting the major gene hypothesis and having parents with informative genotypes and multiple offspring were selected for this linkage analysis. In each of these pedigrees, the recombination fractions maximized at 0 with a positive, albeit low, LOD score. The results of this linkage analysis provide preliminary and suggestive evidence that the cholesterol 7$\alpha$-hydroxylase gene and the inferred gallbladder disease susceptibility gene are genetically linked. ^