Population amalgamation and genetic variation: observations on artificially agglomerated tribal populations of Central and South America.

The interpretation of data on genetic variation with regard to the relative roles of different evolutionary factors that produce and maintain genetic variation depends critically on our assumptions concerning effective population size and the level of migration between neighboring populations. In humans, recent population growth and movements of specific ethnic groups across wide geographic areas mean that any theory based on assumptions of constant population size and absence of substructure is generally untenable. We examine the effects of population subdivision on the pattern of protein genetic variation in a total sample drawn from an artificial agglomerate of 12 tribal populations of Central and South America, analyzing the pooled sample as though it were a single population. Several striking findings emerge. (1) Mean heterozygosity is not sensitive to agglomeration, but the number of different alleles (allele count) is inflated, relative to neutral mutation/drift/equilibrium expectation. (2) The inflation is most serious for rare alleles, especially those which originally occurred as tribally restricted "private" polymorphisms. (3) The degree of inflation is an increasing function of both the number of populations encompassed by the sample and of the genetic divergence among them. (4) Treating an agglomerated population as though it were a panmictic unit of long standing can lead to serious biases in estimates of mutation rates, selection pressures, and effective population sizes. Current DNA studies indicate the presence of numerous genetic variants in human populations. The findings and conclusions of this paper are all fully applicable to the study of genetic variation at the DNA level as well.

A MORTALITY STUDY OF BUTYL-CHLOROBUTYL RUBBER WORKERS

Worker populations are potentially exposed to multiple chemical substances simultaneously during the performance of routine tasks. The acute health effects from exposure to toxic concentrations of these substances are usually well-described. However, very little is known about the long-term health effects of chronic low dose exposure to all except a few chemical substances. A mortality study was performed on a population of workers employed at a butyl rubber manufacturing plant in Baton Rouge, Louisiana for the period 1943-1978, with special emphasis on potential exposure to methyl chloride.^ The study population was enumerated using company records. The mortality experience among the population was evaluated by comparing the number of observed deaths (total and cause-specific) to the expected number of deaths, based on the U.S. general age, race, sex specific rates. An internal comparison population was assembled to address the issue of lack of comparability when the U.S. rates are used to calculate expected deaths in an employed population.^ There were 18% fewer total observed deaths compared to the expected when the U.S. death rates were used to obtain the expected. Deaths from specific causes were also less than expected except when numbers of observed and expected deaths were small. Similar results were obtained when the population was characterized by intensity and duration of potential exposure to methyl chloride. When the internal comparison population was utilized to evaluate overall mortality of the study population, the relative risk was about 1.2.^ The study results were discussed and conclusions drawn in light of certain limitations of the methodology and study population size. ^

An evaluation of the impact of Inner City Development's Cooperative Home School: An educational alternative program to increase the quality and level of education in San Antonio's West Side community

The research study was intended to evaluate the effectiveness of Inner City Development's (I.C.D.) Cooperative Home School, an educational alternative program to the Title I public schools of San Antonio's West Side community. The study investigated students', parents' and tutors' perception of parental involvement and educational resources. The study also investigated each student's academic achievement. ^ The study found that students progressed toward expected math proficiency at a faster rate than they did in reading proficiency. However, because the target population size was small and a comparison group was not used, the results of this study are only suggestive. This research also indicated that study subjects believed students' quality and level of education increased substantially since program exposure. Study subjects mainly attributed the students' strides in academic performance to the increased amount of individualized attention students received in the small twelve-student class size. Study subjects were more satisfied with the home school's educational resources than those of the Title I public schools. Study subjects also perceived that parental involvement both at home and at school increased since enrollment in the home school program because: (1) there were more opportunities for involvement in the home school; and (2) parents felt closer to the tutors than the teachers in public school. ^ This evaluation also suggested improvements to program operations. With the help of additional volunteers, I.C.D. program operators could improve collection and organization of academic records. Furthermore, as suggested by program participants, science could be added to the curriculum. Lastly, a formal tutor orientation could be implemented to familiarize and train tutors on classroom management procedures. ^

A coalescent analysis for modeling the mutation process in colorectal cancer

Colorectal cancer is the forth most common diagnosed cancer in the United States. Every year about a hundred forty-seven thousand people will be diagnosed with colorectal cancer and fifty-six thousand people lose their lives due to this disease. Most of the hereditary nonpolyposis colorectal cancer (HNPCC) and 12% of the sporadic colorectal cancer show microsatellite instability. Colorectal cancer is a multistep progressive disease. It starts from a mutation in a normal colorectal cell and grows into a clone of cells that further accumulates mutations and finally develops into a malignant tumor. In terms of molecular evolution, the process of colorectal tumor progression represents the acquisition of sequential mutations. ^ Clinical studies use biomarkers such as microsatellite or single nucleotide polymorphisms (SNPs) to study mutation frequencies in colorectal cancer. Microsatellite data obtained from single genome equivalent PCR or small pool PCR can be used to infer tumor progression. Since tumor progression is similar to population evolution, we used an approach known as coalescent, which is well established in population genetics, to analyze this type of data. Coalescent theory has been known to infer the sample's evolutionary path through the analysis of microsatellite data. ^ The simulation results indicate that the constant population size pattern and the rapid tumor growth pattern have different genetic polymorphic patterns. The simulation results were compared with experimental data collected from HNPCC patients. The preliminary result shows the mutation rate in 6 HNPCC patients range from 0.001 to 0.01. The patients' polymorphic patterns are similar to the constant population size pattern which implies the tumor progression is through multilineage persistence instead of clonal sequential evolution. The results should be further verified using a larger dataset. ^

Community diagnosis: A working tool for developing culturally appropriate diarrhea intervention programs

Most studies related to diarrhea have been focused narrowly on the etiological and pathophysiological factors involved in inducing the disease. Such studies have often failed to consider other facets contributing to and possibly prolonging the problem, namely: socio-economic conditions, educational opportunities and attainments, cultural characteristics and beliefs, and the political administration and its commitment towards fulfilling its moral and ethical obligations in responding to and fostering human development.^ This study utilized the diagnostic approach of the PRECEDE model. The acronym stands for the predisposing reinforcing, and enabling constructs in educational diagnosis and evaluation. The constituents of this model were identified by utilizing participant observation field methods, traditionally applied by ethnographers to collect data describing the multiple facets of a culture, and linguistic anthropology used to capture and define characteristic semantics and viewpoints. The household study sample was randomly selected from a defined list of households known to have at least one child less than five years of age. An open-ended questionnaire format was used to interview the 115 mothers in the selected households sample.^ Kalama, the study community, is characteristically an agricultural village, situated in the Governorate of Kaliobia and located approximately 25 Km (about 15.5 miles) from the capital, Cairo, Egypt. The 1986 census indicates a population size of 13,328 people in 4,818 households. There were 65 deaths occurring among children less than five years in 1986. The causes of death were primarily related to diarrhea, followed by upper respiratory infections, congenital anomalies and birth injuries.^ This study outlines (a) practices related to the management of diarrhea, including the administration of foods and drinks during such episodes; (b) influences of governmental policies; and (c) recommended strategies for overcoming barriers and promoting effective diarrhea intervention programs. ^

Decomposition of $\rm R\times C$ contingency table chi -square: Application to binned DNA fragment size data and population structure analysis

The purpose of this research is to develop a new statistical method to determine the minimum set of rows (R) in a R x C contingency table of discrete data that explains the dependence of observations. The statistical power of the method will be empirically determined by computer simulation to judge its efficiency over the presently existing methods. The method will be applied to data on DNA fragment length variation at six VNTR loci in over 72 populations from five major racial groups of human (total sample size is over 15,000 individuals; each sample having at least 50 individuals). DNA fragment lengths grouped in bins will form the basis of studying inter-population DNA variation within the racial groups are significant, will provide a rigorous re-binning procedure for forensic computation of DNA profile frequencies that takes into account intra-racial DNA variation among populations. ^

A spatial-temporal approach to surveillance of prostate cancer disparities in population subgroups

BACKGROUND: Prostate cancer mortality disparities exist among racial/ethnic groups in the United States, yet few studies have explored the spatiotemporal trend of the disease burden. To better understand mortality disparities by geographic regions over time, the present study analyzed the geographic variations of prostate cancer mortality by three Texas racial/ethnic groups over a 22-year period. METHODS: The Spatial Scan Statistic developed by Kulldorff et al was used. Excess mortality was detected using scan windows of 50% and 90% of the study period and a spatial cluster size of 50% of the population at risk. Time trend was analyzed to examine the potential temporal effects of clustering. Spatial queries were used to identify regions with multiple racial/ethnic groups having excess mortality. RESULTS: The most likely area of excess mortality for blacks occurred in Dallas-Metroplex and upper east Texas areas between 1990 and 1999; for Hispanics, in central Texas between 1992 and 1996: and for non-Hispanic whites, in the upper south and west to central Texas areas between 1990 and 1996. Excess mortality persisted among all racial/ethnic groups in the identified counties. The second scan revealed that three counties in west Texas presented an excess mortality for Hispanics from 1980-2001. Many counties bore an excess mortality burden for multiple groups. There is no time trend decline in prostate cancer mortality for blacks and non-Hispanic whites in Texas. CONCLUSION: Disparities in prostate cancer mortality among racial/ethnic groups existed in Texas. Central Texas counties with excess mortality in multiple subgroups warrant further investigation.

The Role of Cell Sterilization in Population Based Studies of Radiogenic Second Cancers Following Radiation Therapy

Advances in radiotherapy have generated increased interest in comparative studies of treatment techniques and their effectiveness. In this respect, pediatric patients are of specific interest because of their sensitivity to radiation induced second cancers. However, due to the rarity of childhood cancers and the long latency of second cancers, large sample sizes are unavailable for the epidemiological study of contemporary radiotherapy treatments. Additionally, when specific treatments are considered, such as proton therapy, sample sizes are further reduced due to the rareness of such treatments. We propose a method to improve statistical power in micro clinical trials. Specifically, we use a more biologically relevant quantity, cancer equivalent dose (DCE), to estimate risk instead of mean absorbed dose (DMA). Our objective was to demonstrate that when DCE is used fewer subjects are needed for clinical trials. Thus, we compared the impact of DCE vs. DMA on sample size in a virtual clinical trial that estimated risk for second cancer (SC) in the thyroid following craniospinal irradiation (CSI) of pediatric patients using protons vs. photons. Dose reconstruction, risk models, and statistical analysis were used to evaluate SC risk from therapeutic and stray radiation from CSI for 18 patients. Absorbed dose was calculated in two ways: with (1) traditional DMA and (2) with DCE. DCE and DMA values were used to estimate relative risk of SC incidence (RRCE and RRMA, respectively) after proton vs. photon CSI. Ratios of RR for proton vs. photon CSI (RRRCE and RRRMA) were then used in comparative estimations of sample size to determine the minimal number of patients needed to maintain 80% statistical power when using DCE vs. DMA. For all patients, we found that protons substantially reduced the risk of developing a second thyroid cancer when compared to photon therapy. Mean RRR values were 0.052±0.014 and 0.087±0.021 for RRRMA and RRRCE, respectively. However, we did not find that use of DCE reduced the number of patents needed for acceptable statistical power (i.e, 80%). In fact, when considerations were made for RRR values that met equipoise requirements and the need for descriptive statistics, the minimum number of patients needed for a micro-clinical trial increased from 17 using DMA to 37 using DCE. Subsequent analyses revealed that for our sample, the most influential factor in determining variations in sample size was the experimental standard deviation of estimates for RRR across the patient sample. Additionally, because the relative uncertainty in dose from proton CSI was so much larger (on the order of 2000 times larger) than the other uncertainty terms, it dominated the uncertainty in RRR. Thus, we found that use of corrections for cell sterilization, in the form of DCE, may be an important and underappreciated consideration in the design of clinical trials and radio-epidemiological studies. In addition, the accurate application of cell sterilization to thyroid dose was sensitive to variations in absorbed dose, especially for proton CSI, which may stem from errors in patient positioning, range calculation, and other aspects of treatment planning and delivery.

Relationship between parental feeding practices and weight status in a lower socioeconomic pre-school population

High prevalence of overweight and obesity among preschool children in the low income population is consistently documented in research with one of every seven low-income, preschool-aged children classified as obese. Parental feeding practices have the potential to be contributing factors to the obesity epidemic. However, the impact of parental feeding practices on obesity in preschool age children has not been well explored. The purpose of this study was to determine relationships between the parental feeding practices of using dessert, sweets or candy as a reward for finishing foods, restricting dessert if the child does not finish their plate at dinner, asking the child to consume everything on their plate at dinner, and having family dinners to obesity in low income, preschool age children.^ A cross-sectional secondary data analysis was completed using the STATA 11 statistical software. Descriptive statistics were completed to summarize demographic and BMI data of participants, as well as parental feeding behavior variables. Pearson’s correlation was implemented to determine a correlation between parental feeding behavior variables and BMI z scores. Predictive relationships between the variables were explored through multivariable linear regression analysis. Regression analyses were also completed factoring in the confounders of gender, age, and ethnicity.^ Results revealed (1) no significant correlations or predictive trends between the use of rewards, forced consumption, or family dinner and BMI in low income preschool age children, and (2) a significant negative correlation and predictive trend between restriction of desserts and BMI in low income preschool age children. Since the analysis supported the null hypothesis for the practices of reward use, forced consumption, and family dinner, these practices are not considered risk factors for obese level BMIs. The inverse association found for practice of restriction and BMI suggests it is unnecessary to discourage parents from using restriction. Limitations of the study included the sample size, reliability of the answers provided on the Healthy Home Survey by participant guardians, and generalizability of the sample to the larger population.^

Food availability in the home and dietary intake of the Harris County Department of Education Head Start population

Background. The prevalence of obesity and overweight children has been an ongoing health epidemic in the US for the last several decades. The problem has consistently worsened and has disproportionately been the most prevalent among low socioeconomic status (SES) populations. Food availability in the home has been suggested to be a potential factor related to overweight and obesity, as availability is likely associated with intake. Food availability of low SES preschool aged children has not been well examined. The purpose of this study was to explore the food environment of the Harris County Department of Education (HCDE) Head Start population, and describe reported frequency of intake of particular food groups. The effect of food availability on reported intake was also examined.^ Methods. This was a cross-sectional study of secondary data analysis. Data obtained from 17 HCDE Head Start Centers was analyzed using PASW 18 Statistical Software. Demographic analyses included population, age, gender, race, parent occupation, type of home, and language spoken in the home. Descriptive statistics included reported availability of foods in the home as well as frequency of intake.^ Regression analysis examined the relationship of availability of foods on intake. The food categories included were: dark leafy green and orange vegetables, other vegetables, fruits, soda, salty snacks, and sweet snacks. For both vegetable categories reported intake of fresh, frozen, and canned vegetables were included. For the fruit category, intake of fresh, frozen, canned, and dried fruits were reported.^ Results. Results showed that 90-95% of parents reported having vegetables and fruits available in the home. However, the only significant relationship between availability and intake was for fresh fruit and dried fruit. No associations were seen among the vegetable groups. Other vegetables (bell peppers, eggplant, tomatoes, onions, iceberg lettuce, asparagus) that were frozen, approached significance for availability on intake, however once adjusted for confounders the relationship was no longer present. Among soda, salty snacks, and sweet snacks the only significant relationship was seen for soda availability and intake. Salty snacks and sweet snacks presence in the home was not a predictor of increased frequency of intake.^ Conclusions. This research supported the hypothesis that availability of foods has an impact on intake for fresh fruits, dried fruits and soda. No associations were seen for vegetables, salty snacks and sweet snacks. Additionally, most of the parents reported having fruits and vegetables in the home, but reported intakes were not meeting the Dietary Guidelines for Americans recommendations. Strengths of the study included the large sample size taken from numerous HCDE Head Start Centers. Limitations included questionable reliability of participant’s responses, ability to generalize to other populations, and the use of secondary data rather than prospectively collected data.^

POPULATION ASSESSMENTS OF INFECTION WITH SCHISTOSOMA MANSONI: EFFECTS OF BIAS CAUSED BY THE RELATIVE SENSITIVITY OF DIAGNOSTIC TECHNIQUES (PUERTO RICO)

This study establishes the extent and relevance of bias of population estimates of prevalence, incidence, and intensity of infection with Schistosoma mansoni caused by the relative sensitivity of stool examination techniques. The population studied was Parcelas de Boqueron in Las Piedras, Puerto Rico, where the Centers for Disease Control, had undertaken a prospective community-based study of infection with S. mansoni in 1972. During each January of the succeeding years stool specimens from this population were processed according to the modified Ritchie concentration (MRC) technique. During January 1979 additional stool specimens were collected from 30 individuals selected on the basis of their mean S. mansoni egg output during previous years. Each specimen was divided into ten 1-gm aliquots and three 42-mg aliquots. The relationship of egg counts obtained with the Kato-Katz (KK) thick smear technique as a function of the mean of ten counts obtained with the MRC technique was established by means of regression analysis. Additionally, the effect of fecal sample size and egg excretion level on technique sensitivity was evaluated during a blind assessment of single stool specimen samples, using both examination methods, from 125 residents with documented S. mansoni infections. The regression equation was: Ln KK = 2.3324 + 0.6319 Ln MRC, and the coefficient of determination (r('2)) was 0.73. The regression equation was then utilized to correct the term "m" for sample size in the expression P ((GREATERTHEQ) 1 egg) = 1 - e('-ms), which estimates the probability P of finding at least one egg as a function of the mean S. mansoni egg output "m" of the population and the effective stool sample size "s" utilized by the coprological technique. This algorithm closely approximated the observed sensitivity of the KK and MRC tests when these were utilized to blindly screen a population of known parasitologic status for infection with S. mansoni. In addition, the algorithm was utilized to adjust the apparent prevalence of infection for the degree of functional sensitivity exhibited by the diagnostic test. This permitted the estimation of true prevalence of infection and, hence, a means for correcting estimates of incidence of infection. ^

THE IMPLEMENTATION OF FEDERAL FAMILY PLANNING POLICY: AN ANALYSIS OF FACTORS AFFECTING STATE EXPENDITURES, FISCAL YEARS 1976-1981 (WOMEN, BUDGET, POPULATION)

The purpose of this study was to analyze the implementation of national family planning policy in the United States, which was embedded in four separate statutes during the period of study, Fiscal Years 1976-81. The design of the study utilized a modification of the Sabatier and Mazmanian framework for policy analysis, which defined implementation as the carrying out of statutory policy. The study was divided into two phases. The first part of the study compared the implementation of family planning policy by each of the pertinent statutes. The second part of the study identified factors that were associated with implementation of federal family planning policy within the context of block grants.^ Implemention was measured here by federal dollars spent for family planning, adjusted for the size of the respective state target populations. Expenditure data were collected from the Alan Guttmacher Institute and from each of the federal agencies having administrative authority for the four pertinent statutes, respectively. Data from the former were used for most of the analysis because they were more complete and more reliable.^ The first phase of the study tested the hypothesis that the coherence of a statute is directly related to effective implementation. Equity in the distribution of funds to the states was used to operationalize effective implementation. To a large extent, the results of the analysis supported the hypothesis. In addition to their theoretical significance, these findings were also significant for policymakers insofar they demonstrated the effectiveness of categorical legislation in implementing desired health policy.^ Given the current and historically intermittent emphasis on more state and less federal decision-making in health and human serives, the second phase of the study focused on state level factors that were associated with expenditures of social service block grant funds for family planning. Using the Sabatier-Mazmanian implementation model as a framework, many factors were tested. Those factors showing the strongest conceptual and statistical relationship to the dependent variable were used to construct a statistical model. Using multivariable regression analysis, this model was applied cross-sectionally to each of the years of the study. The most striking finding here was that the dominant determinants of the state spending varied for each year of the study (Fiscal Years 1976-1981). The significance of these results was that they provided empirical support of current implementation theory, showing that the dominant determinants of implementation vary greatly over time. ^

Prevalence and risk factors for Helicobacter pylori in the Ysleta del Sur Pueblo population

Background: Helicobacter pylori infection among Native Americans is more prevalent than any other minority group in the United States. Few studies involving Helicobacter pylori have been conducted on Native Americans and no previous studies have been conducted in the Ysleta del Sur Pueblo population. Therefore we wanted to explore the prevalence and risk factors of Helicobacter pylori within this community. We also explored whether household transmission is occurring. ^ Materials and Methods: We conducted a cross-section study on the prevalence of Helicobacter pylori in the Ysleta del Sur Pueblo community. Main household caregivers were interviewed on household conditions, hygiene practices, and household sociodemographics. All household members were tested for IgG urine antibodies against Helicobacter pylori using RAPIRUN test kits. 13C urea breath testing using BREATHTEK kits was provided to study participants that had positive antibody results and utilized as confirmatory results of infection. ^ Results: Prevalence of Ysleta del Sur Pueblo was determined to be 27.4%. When comparing for ethnicity, Native Americans had increased prevalence of infection then Mexican-Americans living on the Pueblo. That prevalence increased from 1.6 to 3.3 when taking account only United States born study participants. The household secondary prevalence rate was found to be 23.8%. Helicobacter pylori infection rates increased with increasing age and decreasing income. ^ Conclusions: Native Americans had an increased risk of infection. As expected risk factors for Helicobacter pylori correlated with previous studies, but we found evidence of limited current transmission within households. However, due to the limited sample size (n=62) and power, we were not able to find statistical significance for some risk factors. A statistical association was found with age where increasing prevalence corresponded with increasing age suggesting that the birth cohort may be in effect within this population.^

Effects of thymus size and involution on the contribution of recent thymic emigrants to the peripheral T cell pool

The contribution of recent thymic emigrants (RTEs) to the peripheral naïve T cell population is necessary to maintain diversity of the T cell receptor (TCR) repertoire and produce immune responses against newly encountered antigens. The thymus involutes with age, after irradiation or chemotherapy, and due to severe viral infections. Thymus involution results in decreased thymopoiesis and RTE output leading to a reduced diversity of peripheral T cells. This increases susceptibility to disease and impairs immune responsiveness to vaccines. Therefore, studies aimed at maintaining or regenerating thymic function are integral for maintaining and restoring peripheral TCR diversity. Mice that express a K5.CyclinD1 transgene expression have a severely hyperplastic thymus that fails to undergo involution. Both thymocyte and TEC development appear normal in these mice. We have used the K5.CyclinD1 transgenic model to test the hypothesis that preventing thymus involution will sustain RTE output and incorporation into the peripheral T cell pool to prevent naïve T cell depletion with age. The K5.CyclinD1 transgene was crossed to the RAG2p-GFP transgenic model so that RTEs could be tracked by the intensity of the GFP signal. The frequency and number of RTEs in naïve CD4 splenic T cells was analyzed at monthly intervals to 5 months of age. Using this double transgenic approach, we determined that preventing thymus involution does maintain or enhance the number of RTEs in the peripheral T cell pool before and after thymus involution.

Quality of life and functional status in a low -income, multiethnic HIV -positive population

The introduction of new medical treatments in recent years, commonly referred to as highly active antiretroviral therapy, has greatly increased the survival of patients with HIV/AIDS. As patients with HIV/AIDS continue to live longer, other important health-related outcomes, such as quality of life (QOL), should be thoroughly studied. There is also evidence that racial/ethnic minorities are disproportionately affected by HIV/AIDS, but potential health disparities among individuals already infected with HIV/AIDS have not been adequately examined in ethnically diverse populations. The purpose of this dissertation was to: (1) examine the impact of both demographic and behavioral variables on functional status and overall QOL among a population of ethnically diverse and economically disadvantaged HIV/AIDS patients; (2) examine the psychometric properties of a functional status measure—the Household and Leisure Time Activities questionnaire (HLTA); and (3) assess a proximal-distal theoretical framework for QOL using a full structural equation model in a population of patients with HIV/AIDS. Analyses were performed using data collected in the fall of 2000 from the project, Health and Work-Related Quality of Life and Health Risk Behaviors in a Multiethnic HIV-positive Population . Investigators from The University of Texas M.D. Anderson Cancer Center, The University of Texas-Houston Medical School, and The University of Texas School of Public Health conducted this project. The study site was the Thomas Street Clinic (TSC), a comprehensive HIV/AIDS care facility funded by the Harris County Hospital District (HCHD). TSC provides HIV/AIDS care to a diverse population of approximately 4000 medically indigent residents of Harris County. A systematic, consecutive sampling procedure yielded a sample size of 348 patients. Findings suggested that overall QOL, work-role functioning, household functioning, and leisure time functioning were impaired in this patient population. Results from the psychometric evaluation indicated that the HLTA was a reliable and valid measure of household and leisure time functioning status in a low-income multiethnic HIV-positive population. Finally, structural equation modeling of the proximal-distal QOL model suggested that this model was not a viable representation of the relationship between the study variables in this patient population. ^