A novel method for evaluating an interaction effect of correlated continuous covariates in a linear model

Interaction effect is an important scientific interest for many areas of research. Common approach for investigating the interaction effect of two continuous covariates on a response variable is through a cross-product term in multiple linear regression. In epidemiological studies, the two-way analysis of variance (ANOVA) type of method has also been utilized to examine the interaction effect by replacing the continuous covariates with their discretized levels. However, the implications of model assumptions of either approach have not been examined and the statistical validation has only focused on the general method, not specifically for the interaction effect.^ In this dissertation, we investigated the validity of both approaches based on the mathematical assumptions for non-skewed data. We showed that linear regression may not be an appropriate model when the interaction effect exists because it implies a highly skewed distribution for the response variable. We also showed that the normality and constant variance assumptions required by ANOVA are not satisfied in the model where the continuous covariates are replaced with their discretized levels. Therefore, naïve application of ANOVA method may lead to an incorrect conclusion. ^ Given the problems identified above, we proposed a novel method modifying from the traditional ANOVA approach to rigorously evaluate the interaction effect. The analytical expression of the interaction effect was derived based on the conditional distribution of the response variable given the discretized continuous covariates. A testing procedure that combines the p-values from each level of the discretized covariates was developed to test the overall significance of the interaction effect. According to the simulation study, the proposed method is more powerful then the least squares regression and the ANOVA method in detecting the interaction effect when data comes from a trivariate normal distribution. The proposed method was applied to a dataset from the National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator (t-PA) stroke trial, and baseline age-by-weight interaction effect was found significant in predicting the change from baseline in NIHSS at Month-3 among patients received t-PA therapy.^

Selection bias and the cross-validation of regression models for prediction

Strategies are compared for the development of a linear regression model with stochastic (multivariate normal) regressor variables and the subsequent assessment of its predictive ability. Bias and mean squared error of four estimators of predictive performance are evaluated in simulated samples of 32 population correlation matrices. Models including all of the available predictors are compared with those obtained using selected subsets. The subset selection procedures investigated include two stopping rules, C$\sb{\rm p}$ and S$\sb{\rm p}$, each combined with an 'all possible subsets' or 'forward selection' of variables. The estimators of performance utilized include parametric (MSEP$\sb{\rm m}$) and non-parametric (PRESS) assessments in the entire sample, and two data splitting estimates restricted to a random or balanced (Snee's DUPLEX) 'validation' half sample. The simulations were performed as a designed experiment, with population correlation matrices representing a broad range of data structures.^ The techniques examined for subset selection do not generally result in improved predictions relative to the full model. Approaches using 'forward selection' result in slightly smaller prediction errors and less biased estimators of predictive accuracy than 'all possible subsets' approaches but no differences are detected between the performances of C$\sb{\rm p}$ and S$\sb{\rm p}$. In every case, prediction errors of models obtained by subset selection in either of the half splits exceed those obtained using all predictors and the entire sample.^ Only the random split estimator is conditionally (on $\\beta$) unbiased, however MSEP$\sb{\rm m}$ is unbiased on average and PRESS is nearly so in unselected (fixed form) models. When subset selection techniques are used, MSEP$\sb{\rm m}$ and PRESS always underestimate prediction errors, by as much as 27 percent (on average) in small samples. Despite their bias, the mean squared errors (MSE) of these estimators are at least 30 percent less than that of the unbiased random split estimator. The DUPLEX split estimator suffers from large MSE as well as bias, and seems of little value within the context of stochastic regressor variables.^ To maximize predictive accuracy while retaining a reliable estimate of that accuracy, it is recommended that the entire sample be used for model development, and a leave-one-out statistic (e.g. PRESS) be used for assessment. ^

Adiposity and the perilipin gene: The role of single locus and multilocus variation, obesity-related quantitative traits, and disease-related phenotypes in the Atherosclerosis Risk in Communities (ARIC) study

Obesity is a complex multifactorial disease and is a public health priority. Perilipin coats the surface of lipid droplets in adipocytes and is believed to stabilize these lipid bodies by protecting triglyceride from early lipolysis. This research project evaluated the association between genetic variation within the human perilipin (PLIN) gene and obesity-related quantitative traits and disease-related phenotypes in Non-Hispanic White (NHW) and African American (AA) participants from the Atherosclerosis Risk in Communities (ARIC) Study. ^ Multivariate linear regression, multivariate logistic regression, and Cox proportional hazards models evaluated the association between single gene variants (rs2304794, rs894160, rs8179071, and rs2304795) and multilocus variation (rs894160 and rs2304795) within the PLIN gene and both obesity-related quantitative traits (body weight, body mass index [BMI], waist girth, waist-to-hip ratio [WHR], estimated percent body fat, and plasma total triglycerides) and disease-related phenotypes (prevalent obesity, metabolic syndrome [MetS], prevalent coronary heart disease [CHD], and incident CHD). Single variant analyses were stratified by race and gender within race while multilocus analyses were stratified by race. ^ Single variant analyses revealed that rs2304794 and rs894160 were significantly related to plasma triglyceride levels in all NHWs and NHW women. Among AA women, variant rs8179071 was associated with triglyceride levels and rs2304794 was associated with risk-raising waist circumference (>0.8 in women). The multilocus effects of variants rs894160 and rs2304795 were significantly associated with body weight, waist girth, WHR, estimated percent body fat, class II obesity (BMI ≥ 35 kg/m2), class III obesity (BMI ≥ 35 kg/m2), and risk-raising WHR (>0.9 in men and >0.8 in women) in AAs. Variant rs2304795 was significantly related to prevalent MetS among AA males and prevalent CHD in NHW women; multilocus effects of the PLIN gene were associated with prevalent CHD among NHWs. Rs2304794 was associated with incident CHD in the absence of the MetS among AAs. These findings support the hypothesis that variation within the PLIN gene influences obesity-related traits and disease-related phenotypes. ^ Understanding these effects of the PLIN genotype on the development of obesity can potentially lead to tailored health promotion interventions that are more effective. ^

A cross-sectional analysis of physical activity and obesity in inner city Houston Texas Mexican American youth

Obesity prevalence among children and adolescents is rising. It is one of the most attributable causes of hospitalization and death. Overweight and obese children are more likely to suffer from associated conditions such as hypertension, dyslipidemia, chronic inflammation, increased blood clotting tendency, endothelial dysfunction, hyperinsulinemia, and asthma. These children and adolescents are also more likely to be overweight and obese in adulthood. Interestingly, rates of obesity and overweight are not evenly distributed across racial and ethnic groups. Mexican American youth have higher rates of obesity and are at higher risk of becoming obese than non-Hispanic black and non-Hispanic white children. ^ Methods. This cross-sectional study describes the association between rates of obesity and physical activity in a sample of 1313 inner-city Mexican American children and adolescents (5-19 years of age) in Houston, Texas. This study is important because it will contribute to our understanding of childhood and adolescent obesity in this at-risk population. ^ Data from the Mexican American Feasibility Cohort using the Mano a Mano questionnaire are used to describe this population's status of obesity and physical activity. An initial sample taken from 5000 households in inner city Houston Texas was used as the baseline for this prospective cohort. The questionnaire was given in person to the participants to complete (or to parents for younger children) at a home visit by two specially trained bilingual interviewers. Analysis comprised prevalence estimates of obesity represented as percentile rank (<85%= normal weight, >85%= at risk, >95%= obese) by age and gender. The association between light, moderate, strenuous activity, and obesity was also examined using linear regression. ^ Results. Overall, 46% of this Mexican American Feasibility cohort is overweight or obese. The prevalence for children in the 6-11 age range (53.2%) was significantly greater than that reported from NHANES, 1999–2002 data (39.4%). Although the percentage of overweight and obese among the 12-19 year olds was greater than that reported in NHANES (38.5% versus 38.6%) this difference was not statistically significant. ^ A significant association between BMI and sit time and moderate physical activity (both p < 0.05) found in this sample. For males, this association was significant for moderate physical activity (p < 0.01). For the females, this association was significant for BMI and sit time (p < 0.05). These results need to be interpreted in the light of design and measurement limitations. ^ Conclusion. This study supports observations that the inner city Houston Texas Mexican American child and adolescent population is more overweight and obese than nationally reported figures, and that there are positive relationships between BMI, activity levels, and sit time in this population. This study supports the need for public health initiatives within the Houston Hispanic community. ^

Impact of oral contraceptives on weight, body composition, and cardiovascular disease risk factors in women age 18--30 years participating in a 15-week exercise program

Objective. To assess differences in body weight, body composition, total cholesterol, blood pressure, and blood glucose between OC users and non-users age 18-30 y before and after a 15-week cardiovascular exercise program in Houston, TX from 2003 to 2007.^ Study Design. Secondary analysis of prospective data. ^ Study Subjects. 453 Non-Hispanic white (NHW), Hispanic, and African American (AA) women age 18-30 y with no previous live birth, a history of menstruating, no use of other hormonal contraceptives or medications, no menopause or hysterectomy, and no current pregnancies.^ Measurements. Demographic data, medication use, and menstrual history were assessed via self-administered questionnaires at baseline. Anthropometric and laboratory measures were taken at baseline and 15-weeks. ^ Data Analysis. Linear regression assessed the association between OC use and study variables at baseline, and the change in study variables from baseline to 15-weeks. Logistic regression assessed the association between OC use and CVD risk. Each analysis was also stratified by race/ethnicity. ^ Results. At baseline, OC users had higher total cholesterol (p<.0005) and were above cholesterol risk cut points for CVD (OR=4.3, 95% CI=2.4-7.7) compared to non-users. At baseline, OC use was also associated with higher diastolic blood pressure (p=.018) compared to non-users, primarily in non-Hispanic whites (p=.007). OC use was associated with lower blood glucose compared to non-users in Hispanics only (p=.008). OC use was associated with absolute change in diastolic blood pressure (p=.044) and total cholesterol (p=.003). There was evidence that OC use may affect individuals differently based on race/ethnicity for certain obesity and CVD risk factors.^ Conclusions. OC users and non-users responded similarly to a 15-week cardiovascular exercise program. Exceptions included a greater change in diastolic blood pressure and total cholesterol among NHW and Hispanic OC users compared to non-users after exercise intervention. At baseline, OC use was associated with diastolic blood pressure and was most strongly associated with increased levels of total cholesterol. OC users were at greater risk of having total cholesterol above CVD risk cut points than non-users.^

A space-time analysis of reported shigellosis and salmonellosis cases in Texas from 2000 to 2004

Background. The purpose of this study was to describe the risk factors and demographics of persons with salmonellosis and shigellosis and to investigate both seasonal and spatial variations in the occurrence of these infections in Texas from 2000 to 2004, utilizing time series analyses and the geographic information system digital mapping methods. ^ Methods. Spatial Analysis: MapInfo software was used to map the distribution of age-adjusted rates of reported shigellosis and salmonellosis in Texas from 2000–2004 by zip codes. Census data on above or below poverty level, household income, highest level of educational attainment, race, ethnicity, and urban/rural community status was obtained from the 2000 Decennial Census for each zip code. The zip codes with the upper 10% and lower 10% were compared using t-tests and logistic regression to determine whether there were any potential risk factors. ^ Temporal analysis. Seasonal patterns in the prevalence of infections in Texas from 2000 to 2003 were determined by performing time-series analysis on the numbers of cases of salmonellosis and shigellosis. A linear regression was also performed to assess for trends in the incidence of each disease, along with auto-correlation and multi-component cosinor analysis. ^ Results. Spatial analysis: Analysis by general linear model showed a significant association between infection rates and age, with young children aged less than 5 and those aged 5–9 years having increased risk of infection for both disease conditions. The data demonstrated that those populations with high percentages of people who attained a higher than high school education were less likely to be represented in zip codes with high rates of shigellosis. However, for salmonellosis, logistic regression models indicated that when compared to populations with high percentages of non-high school graduates, having a high school diploma or equivalent increased the odds of having a high rate of infection. ^ Temporal analysis. For shigellosis, multi-component cosinor analyses were used to determine the approximated cosine curve which represented a statistically significant representation of the time series data for all age groups by sex. The shigellosis results show 2 peaks, with a major peak occurring in June and a secondary peak appearing around October. Salmonellosis results showed a single peak and trough in all age groups with the peak occurring in August and the trough occurring in February. ^ Conclusion. The results from this study can be used by public health agencies to determine the timing of public health awareness programs and interventions in order to prevent salmonellosis and shigellosis from occurring. Because young children depend on adults for their meals, it is important to increase the awareness of day-care workers and new parents about modes of transmission and hygienic methods of food preparation and storage. ^

Whence a healthy mind: Correlation of physical fitness and academic performance among schoolchildren

Background. Public schools are a key forum in the fight for child health because of the opportunities they present for physical activity and fitness surveillance. However, because schools are evaluated and funded on the basis of standardized academic performance rather than physical activity, empirical research evaluating the connections between fitness and academic performance is needed to justify curriculum allocations to physical activity. ^ Methods. Analyses were based on a convenience sample of 315,092 individually-matched standardized academic (TAKS™) and fitness (FITNESSGRAM®) test records collected by 13 Texas school districts under state mandates. We categorized each fitness result in quintiles by age and gender and used a mixed effects regression model to compare the academic performance of the top and bottom fitness groups for each fitness test and grade level combination. ^ Results. All fitness variables except BMI showed significant, positive associations with academic performance after sociodemographic covariate adjustments, with effect sizes ranging from 0.07 (95% CI: 0.05,0.08) in girls trunklift-TAKS reading to 0.34 (0.32,0.35) in boys cardiovascular-TAKS math. Cardiovascular fitness showed the largest inter-quintile difference in TAKS score (32-75 points), followed by curl-ups. After an additional adjustment for BMI and curl-ups, cardiovascular associations peaked in 8th-9 th grades (maximum inter-quintile difference 142 TAKS points; effect size 0.75 (0.69,0.82) for 8th grade girls math) and showed dose-response characteristics across quintiles (p<0.001 for both genders and outcomes). BMI analysis demonstrated limited, non-linear association with academic performance after adjustment for sociodemographic, cardiovascular fitness and curl-up variables. Low-BMI Hispanic high school boys showed significantly lower TAKS scores than the moderate (but not high) BMI group. High-BMI non-Hispanic white high school girls showed significantly lower scores than the moderate (but not low) BMI group. ^ Conclusions. In this study, fitness was strongly and significantly related to academic performance. Cardiovascular fitness showed a distinct dose-response association with academic performance independent of other sociodemographic and fitness variables. The association peaked in late middle to early high school. The independent association of BMI to academic performance was only found in two sub-groups and was non-linear, with both low and high BMI posing risk relative to moderate BMI but not to each other. In light of our findings, we recommend that policymakers consider PE mandates in middle-high school and require linkage of academic and fitness records to facilitate longitudinal surveillance. School administrators should consider increasing PE time in pursuit of higher academic test scores, and PE practitioners should emphasize cardiovascular fitness over BMI reduction.^

Health significance of chlorination byproducts in drinking water: The Houston experience: A continuation study

Background. Houston, Texas, once obtained all its drinking water from underground sources. However, in 1853, the city began supplementing its water from the surface source Lake Houston. This created differences in the exposure to disinfection byproducts (DBPs) in different parts of Houston. Trihalomethanes (THMs) are the most common DBP and are useful indicators of DBPs in treated drinking water. This study examines the relationship between THMs in chlorinated drinking water and the incidence of bladder cancer in Houston. ^ Methods. Individual bladder cancer deaths, from 1975 to 2004, were assigned to four surface water exposure areas in Houston utilizing census tracts—area A used groundwater the longest, area B used treated lake water the longest, area C used treated lake water the second longest, and area D used a combination of groundwater and treated lake water. Within each surface water exposure area mortality rates were calculated in 5 year intervals by four race-gender categories. Linear regression models were fitted to the bladder cancer mortality rates over the entire period of available data (1990–2004). ^ Results. A decrease in bladder cancer mortality was observed amongst white males in area B (p = 0.030), white females in area A (p = 0.008), non-white males in area D (p = 0.003), and non-white females in areas A and B (p = 0.002 & 0.001). Bladder cancer mortality differed by race-gender and time (p ≤ 0.001 & p ≤ 0.001), but not by surface water exposure area (p = 0.876). ^ Conclusion. The relationship between bladder cancer mortality and the four surface water exposure areas (signifying THM exposure) was insignificant. This result could be attributable to Houston controlling for THMs starting in the early 1980’s by using chloramine as a secondary disinfectant in the drinking water purification process.^

Micronutrient intakes and their associations with markers of inflammation, subclinical atherosclerosis, cardiovascular disease, type II diabetes and metabolic syndrome

We investigated cross-sectional associations between intakes of zinc, magnesium, heme- and non heme iron, beta-carotene, vitamin C and vitamin E and inflammation and subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). We also investigated prospective associations between those micronutrients and incident MetS, T2D and CVD. Participants between 45-84 years of age at baseline were followed between 2000 and 2007. Dietary intake was assessed at baseline using a 120-item food frequency questionnaire. Multivariable linear regression and Cox proportional hazard regression models were used to evaluate associations of interest. Dietary intakes of non-heme iron and Mg were inversely associated with tHcy concentrations (geometric means across quintiles: 9.11, 8.86, 8.74, 8.71, and 8.50 µmol/L for non-heme iron, and 9.20, 9.00, 8.65, 8.76, and 8.33 µmol/L for Mg; ptrends <0.001). Mg intake was inversely associated with high CC-IMT; odds ratio (95% CI) for extreme quintiles 0.76 (0.58, 1.01), ptrend: 0.002. Dietary Zn and heme-iron were positively associated with CRP (geometric means: 1.73, 1.75, 1.78, 1.88, and 1.96 mg/L for Zn and 1.72, 1.76, 1.83, 1.86, and 1.94 mg/L for heme-iron). In the prospective analysis, dietary vitamin E intake was inversely associated with incident MetS and with incident CVD (HR [CI] for extreme quintiles - MetS: 0.78 [0.62-0.97] ptrend=0.01; CVD: 0.69 [0.46-1.03]; ptrend =0.04). Intake of heme-iron from red meat and Zn from red meat, but not from other sources, were each positively associated with risk of CVD (HR [CI] - heme-iron from red meat: 1.65 [1.10-2.47] ptrend = 0.01; Zn from red meat: 1.51 [1.02 - 2.24] ptrend =0.01) and MetS (HR [CI] - heme-iron from red meat: 1.25 [0.99-1.56] ptrend =0.03; Zn from red meat: 1.29 [1.03-1.61]; ptrend = 0.04). All associations evaluated were similar across different strata of gender, race-ethnicity and alcohol intake. Most of the micronutrients investigated were not associated with the outcomes of interest in this multi-ethnic cohort. These observations do not provide consistent support for the hypothesized association of individual nutrients with inflammatory markers, MetS, T2D, or CVD. However, nutrients consumed in red meat, or consumption of red meat as a whole, may increase risk of MetS and CVD.^

Percutaneous transluminal coronary angioplasty and coronary events in a biethnic Texas community, 1985--1990

The relationship between change in myocardial infarction (MI) mortality rate (ICD codes 410, 411) and change in use of percutaneous transluminal coronary angioplasty (PTCA), adjusted for change in hospitalization rates for MI, and for change in use of aortocoronary bypass surgery (ACBS) from 1985 through 1990 at private hospitals was examined in the biethnic community of Nueces County, Texas, site of the Corpus Christi Heart Project, a major coronary heart disease (CHD) surveillance program. Age-adjusted rates (per 100,000 persons) were calculated for each of these CHD events for the population aged 25 through 74 years and for each of the four major sex-ethnic groups: Mexican-American and Non-Hispanic White women and men. Over this six year period, there were 541 MI deaths, 2358 MI hospitalizations, 816 PTCA hospitalizations, and 920 ACBS hospitalizations among Mexican-American and Non-Hispanic White Nueces County residents. Acute MI mortality decreased from 24.7 in the first quarter of 1985 to 12.1 in the fourth quarter of 1990, a 51.2% decrease. All three hospitalization rates increased: The MI hospitalization rates increased from 44.1 to 61.3, a 38.9% increase, PTCA use increased from 7.1 to 23.2, a 228.0% increase, and ACBS use increased from 18.8 to 29.5, a 56.6% increase. In linear regression analyses, the change in MI mortality rate was negatively associated with the change in PTCA use (beta = $-$.266 $\pm$.103, p = 0.017) but was not associated with the changes in MI hospitalization rate and in ACBS use. The results of this ecologic research support the idea that the increasing use of PTCA, but not ACBS, has been associated with decreases in MI mortality. The contrast in associations between these two revascularization procedures and MI mortality highlights the need for research aimed at clarifying the proper roles of these procedures in the treatment of patients with CHD. The association between change in PTCA use and change in MI mortality supports the idea that some changes in medical treatment may be partially responsible for trends in CHD mortality. Differences in the use of therapies such as PTCA may be related to differences between geographical sites in CHD rates and trends. ^

The role of serotonin in depression and clotting in the coronary artery disease population

Background: The mechanisms underlying the relationship between depression and acute coronary syndrome (ACS) remain unclear. Platelet serotonin has been associated with both depression and coronary artery disease in stable outpatients. Understanding the association between depression and platelet serotonin, during ACS, may explain some of the acute cardiovascular events seen in some individuals with depression. ^ Objectives: This study was designed to evaluate whether levels of platelet serotonin, during ACS, differ between individuals who screen positive for depression and individuals who screen negative for depression and to determine if a dose-response relationship exists between depressive symptoms and platelet serotonin levels. ^ Methods: In this cross-sectional study, data was collected on 51 patients hospitalized for ACS. Multiple linear regression models were used to determine if a relationship exists between depression and platelet serotonin levels. ^ Results: Of the 51 ACS patients, 24 screened positive for depression and 27 screened negative for depression. Platelet serotonin levels were not significantly different between the depressed group (942.10 ± 461.3) and the non-depressed group (1192.41 ± 764.3) (p= .293 and β= -4.093) and a dose-response relationship between depressive symptoms and platelet serotonin levels was not found (p= .250 and β= -.254). ^ Discussion: In this study, a relationship between depression and platelet serotonin levels was not found. Future research should focus on gaining a better understanding of the variables that may influence platelet serotonin levels in the ACS population. ^

Prevalence of symptoms of neurotoxicity and potential occupational pesticide and solvent exposures among high school students in Starr County, Texas: A pilot study

Numerous harmful occupational exposures affect working teens in the United States. Teens working in agriculture and other heavy-labor industries may be at risk for occupational exposures to pesticides and solvents. The neurotoxicity of pesticides and solvents at high doses is well-known; however, the long term effects of these substances at low doses on occupationally exposed adolescents have not been well-studied. To address this research gap, a secondary analysis of cross-sectional data was completed in order to estimate the prevalence of self-reported symptoms of neurotoxicity among a cohort of high school students from Starr County, Texas, a rural area along the Texas-Mexico border. Multivariable linear regression was used to estimate the association between work status (i.e., no work, farm work, and non-farm work) and symptoms of neurotoxicity, while controlling for age, gender, Spanish speaking preference, inhalant use, tobacco use, and alcohol use. The sample included 1,208 students. Of these, the majority (85.84%) did not report having worked during the prior nine months compared to 4.80% who did only farm work, 6.21% who did only non-farm work, and 3.15% who did both types of work. On average, students reported 3.26 symptoms with a range from 0-16. The most commonly endorsed items across work status were those related to memory impairment. Adolescents employed in non-farm work jobs reported more neurotoxicity symptoms than those who reported that they did not work (Mean 4.31; SD 3.97). In the adjusted multivariable regression model, adolescents reporting non-farm work status reported an average of 0.77 more neurotoxicity symptoms on the Q16 than those who did not work (P = 0.031). The confounding variables included in the final model were all found to be factors significantly associated with report of neurotoxicity symptoms. Future research should examine the relationship between these variables and self-report of symptoms of neurotoxicity.^

Identification of genetic variants that influence atherosclerosis in young persons

Atherosclerosis is widely accepted as a complex genetic phenotype and is the usual cause of cardiovascular disease, the world’s leading killer. Genetic factors have been proven to be important risk contributors for atherosclerosis and much work has been done to identify promising candidates that might play a role in the development of atherosclerosis. It is well known that many independent replications are needed to unequivocally establish a valid genotype-phenotype association across different populations before the findings are extended to clinical settings and to the expensive follow-up studies designed to identify causal genetic variants. Aiming to replicate the association with atherosclerosis in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we assessed the relationship of 32 atherosclerosis candidate SNPs to atherosclerosis in the PDAY cohort, consisting of AA and EA young people aged 15-34 years who died of non-medical causes. Two association studies, a whole sample study and a 1:1 matched case control study were performed by use of multiple linear regression and logistic regression analyses, respectively. For the whole sample association study, 32 SNPs among 2,650 individuals (1,369 AA and 1,281 EA) were tested for the association with six early atherosclerosis phenotypes: abdominal aorta fatty streaks, abdominal aorta raised lesions, right coronary artery fatty streaks, right coronary artery raised lesions, thoracic aorta fatty streaks, and thoracic aorta raised lesions. For the matched case-control association study, 337 case-control paired samples were included; cases were chosen with the highest total raised lesion scores from the studied population, while controls were randomly selected from individuals that had no raised lesions and matched to cases by age, gender and race. Sixteen SNPs in 13 genes were found to be significantly associated with atherosclerosis in at least one of the PDAY association studies. Among these 16 findings: eight SNPs (rs9579646, rs6053733, rs3849150, rs10499903, rs2148079, rs5073691, rs10116277, and rs17228212) successfully replicated previous results, six SNPs (rs17222814, rs10811661, rs7028570, rs7291467, rs16996148 and rs10401969) were reported as new findings exclusive to our study, the last two of the 16 SNPs, rs501120 and rs6922269, showed either intriguing or conflicting result. SNP rs17222814 in ALOX5AP and SNP rs3849150 in LRRC18 were consistently associated with atherosclerosis in both prior and the two PDAY association studies. SNP rs3849150 was also identified to be highly correlated with a non-synonymous coding SNP, rs17772611, which may damage the protein (polyphen score = 0.996), suggesting that SNP rs17772611 may be the causal functional variant.^ In conclusion, our study added more support for the association of these candidate genes with atherosclerosis. SNPs rs3849150 and rs17772611 of LRRC18, as well as SNP rs17222814 of ALOX5AP, were the most significant findings from our study, and may be ranked among the best for further study.^

Assessing how middle school students' nutrient intake varies based on the availability of a la carte offerings at lunch

Purpose: School districts in the U.S. regularly offer foods that compete with the USDA reimbursable meal, known as `a la carte' foods. These foods must adhere to state nutritional regulations; however, the implementation of these regulations often differs across districts. The purpose of this study is to compare two methods of offering a la carte foods on student's lunch intake: 1) an extensive a la carte program in which schools have a separate area for a la carte food sales, that includes non-reimbursable entrees; and 2) a moderate a la carte program, which offers the sale of a la carte foods on the same serving line with reimbursable meals. ^ Methods: Direct observation was used to assess children's lunch consumption in six schools, across two districts in Central Texas (n=373 observations). Schools were matched on socioeconomic status. Data collectors were randomly assigned to students, and recorded foods obtained, foods consumed, source of food, gender, grade, and ethnicity. Observations were entered into a nutrient database program, FIAS Millennium Edition, to obtain nutritional information. Differences in energy and nutrient intake across lunch sources and districts were assessed using ANOVA and independent t-tests. A linear regression model was applied to control for potential confounders. ^ Results: Students at schools with extensive a la carte programs consumed significantly more calories, carbohydrates, total fat, saturated fat, calcium, and sodium compared to students in schools with moderate a la carte offerings (p<.05). Students in the extensive a la carte program consumed approximately 94 calories more than students in the moderate a la carte program. There was no significant difference in the energy consumption in students who consumed any amount of a la carte compared to students who consumed none. In both districts, students who consumed a la carte offerings were more likely to consume sugar-sweetened beverages, sweets, chips, and pizza compared to students who consumed no a la carte foods. ^ Conclusion: The amount, type and method of offering a la carte foods can significantly affect student dietary intake. This pilot study indicates that when a la carte foods are more available, students consume more calories. Findings underscore the need for further investigation on how availability of a la carte foods affects children's diets. Guidelines for school a la carte offerings should be maximized to encourage the consumption of healthful foods and appropriate energy intake.^

A comparison of adherence with minocycline treatment in Parkinson's disease and rheumatoid arthritis clinical trials

Background: Little is known about the effects on patient adherence when the same study drug is administered in the same dose in two populations with two different diseases in two different clinical trials. The Minocycline in Rheumatoid Arthritis (MIRA) trial and the NIH Exploratory Trials in Parkinson's disease (NET-PD) Futility Study I provide a unique opportunity to do the above and to compare methods measuring adherence. This study may increase understanding of the influence of disease and adverse events on patient adherence and will provide insights to investigators selecting adherence assessment methods in clinical trials of minocycline and other drugs in future.^ Methods: Minocycline adherence by pill count and the effect of adverse events was compared in the MIRA and NET-PD FS1 trials using multivariable linear regression. Within the MIRA trial, agreement between assay and pill count was compared. The association of adverse events with assay adherence was examined using multivariable logistic regression.^ Results: Adherence derived from pill count in the MIRA and NET-PD FS1 trials did not differ significantly. Adverse events potentially related to minocycline did not appear useful to predict minocycline adherence. In the MIRA trial, adherence measured by pill count appears higher than adherence measured by assay. Agreement between pill count and assay was poor (kappa statistic = 0.25).^ Limitations: Trial and disease are completely confounded and hence the independent effect of disease on adherence to minocycline treatment cannot be studied.^ Conclusion: Simple pill count may be preferred over assay in the minocycline clinical trials to measure adherence. Assays may be less sensitive in a clinical setting where appointments are not scheduled in relation to medication administration time, given assays depend on many pharmacokinetic and instrument-related factors. However, pill count can be manipulated by the patient. Another study suggested that self-report method is more sensitive than pill count method in differentiating adherence from non-adherence. An effect of medication-related adverse events on adherence could not be detected.^