Adherence to adjuvant chemotherapy and post-treatment surveillance in a large community-based cohort of patients with colon cancer

The objective of this dissertation was to determine the initiation and completion rates of adjuvant chemotherapy, its toxicity and the compliance rates of post-treatment surveillance for elderly patients with colon cancer using the linked Surveillance, Epidemiology, and End Results – Medicare database.^ The first study assessed the initiation and completion rate of 5-fluorouracil-based adjuvant chemotherapy and its relationship with patient characteristics. Of the 12,265 patients diagnosed with stage III colon adenocarcinoma in 1991-2005, 64.4% received adjuvant chemotherapy within 3-months after tumor resection and 40% of them completed the treatment. Age, marital status, and comorbidity score were significant predictors for chemotherapy initiation and completion.^ The second study estimated the incidence rate of toxicity-related endpoints among stage III colon adenocarcinoma patients treated with chemotherapy in 1991-2005. Of the 12,099 patients, 63.9% underwent chemotherapy and had volume depletion disorder (3-month cumulative incidence rate [CIR]=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Cox regression analysis confirmed such association (HR=2.76; 95% CI=2.42-3.15). The risk of ischemic heart diseases was slightly associated with chemotherapy (HR=1.08), but significantly among patients aged <75 with no comorbidity (HR=1.70). ^ The third study determined the adherence rate of follow-up cares among patients diagnosed with stage I-III colon adenocarcinoma in 2000 - June 2002. We identified 7,348 patients with a median follow-up of 59 months. The adherence rate was 83.9% for office visits, 29.4% for CEA tests, and 74.3% for colonoscopy. Overall, 25.2% met the recommended post-treatment care. Younger age at diagnosis, white race, married, advanced stage, fewer comorbidities, and chemotherapy use were significantly associated with guideline adherence.^ In conclusions, not all colon cancer patients received chemotherapy. Receiving chemotherapy was associated with increased risk of developing gastrointestinal, hematological and cardiac toxicities. Patients were more likely to comply with the schedule for office visits and colonoscopy but failed in CEA tests. ^

Performance tiers: Implementing comparative effectiveness analysis in the health care setting through operations research and spatial methods

This dissertation develops and tests a comparative effectiveness methodology utilizing a novel approach to the application of Data Envelopment Analysis (DEA) in health studies. The concept of performance tiers (PerT) is introduced as terminology to express a relative risk class for individuals within a peer group and the PerT calculation is implemented with operations research (DEA) and spatial algorithms. The analysis results in the discrimination of the individual data observations into a relative risk classification by the DEA-PerT methodology. The performance of two distance measures, kNN (k-nearest neighbor) and Mahalanobis, was subsequently tested to classify new entrants into the appropriate tier. The methods were applied to subject data for the 14 year old cohort in the Project HeartBeat! study.^ The concepts presented herein represent a paradigm shift in the potential for public health applications to identify and respond to individual health status. The resultant classification scheme provides descriptive, and potentially prescriptive, guidance to assess and implement treatments and strategies to improve the delivery and performance of health systems. ^

Demographic analysis of Certified Industrial Hygienists (CIH) with the use of survival analysis techniques

Objective. The goal of this study is to characterize the current workforce of CIHs, the lengths of professional practice careers of the past and current CIHs.^ Methods. This is a secondary data analysis of data compiled from all of the nearly 50 annual roster listings of the American Board of Industrial Hygiene (ABIH) for Certified Industrial Hygienists active in each year since 1960. Survival analysis was performed as a technique to measure the primary outcome of interest. The technique which was involved in this study was the Kaplan-Meier method for estimating the survival function.^ Study subjects: The population to be studied is all Certified Industrial Hygienists (CIHs). A CIH is defined by the ABIH as an individual who has achieved the minimum requirements for education, working experience and through examination, has demonstrated a minimum level of knowledge and competency in the prevention of occupational illnesses. ^ Results. A Cox-proportional hazards model analysis was performed by different start-time cohorts of CIHs. In this model we chose cohort 1 as the reference cohort. The estimated relative risk of the event (defined as retirement, or absent from 5 consecutive years of listing) occurred for CIHs for cohorts 2,3,4,5 relative to cohort 1 is 0.385, 0.214, 0.234, 0.299 relatively. The result show that cohort 2 (CIHs issued from 1970-1980) has the lowest hazard ratio which indicates the lowest retirement rate.^ Conclusion. The manpower of CIHs (still actively practicing up to the end of 2009) increased tremendously starting in 1980 and grew into a plateau in recent decades. This indicates that the supply and demand of the profession may have reached equilibrium. More demographic information and variables are needed to actually predict the future number of CIHs needed. ^

Effects of breastfeeding and naturally acquired immunity on infection with {\it Giardia lamblia}: A study in a cohort of Mexican infants

Giardia lamblia is one of the most common causes of gastrointestinal tract infection among young children worldwide. Yet host protection against this parasite and the effect of infection with Giardia on infant growth are poorly understood. It was hypothesized that among young children, protection against infection with Giardia is afforded by breastfeeding and previous infection with the parasite and further, that infection with Giardia decreases growth velocity. From 4/88 to 4/90, 197 infants in a poor area of Mexico City were followed from 0 to 18 months of age, with stool specimens, symptoms and feeding status data collected weekly. A total of 6,031 stool specimens were tested for Giardia antigen by enzyme-linked immunosorbent assay. There were 1.0 Giardia infections per child-year; 25% were symptomatic and 54% lasted more than 1 month; 94 infants had 1, and 33 had 2 or more infections. Breastfeeding status was coded and analyzed for each child-week of follow up. 91% of study infants were breastfed from birth, 57% at 6 months and 38% at 12 months of age. Rate ratios for non-breastfeeding adjusted for confounding factors were calculated from stratified analyses and the Cox proportional hazards model. Not breastfeeding was a significant risk factor for first infection with Giardia vs. any breastfeeding (adjusted RR = 1.8; 1.1, 2.8) at all ages; a dose response was demonstrated by degree of breastfeeding. The adjusted rate ratio for non-breastfeeding vs. partial breastfeeding was 1.6 (1.03, 2.6) and for non-breastfeeding vs. complete breastfeeding was 4.7 (1.4, 15.9). Among Giardia infected infants, breastfeeding did not protect against diarrheal symptoms or shorten the duration of carriage. First and repeat infections with Giardia did not differ in duration or the percent symptomatic. The analysis of growth and Giardia infection was inconclusive but suggested that a history of Giardia infection might be associated with decreased weight velocity, while an immediate chronic infection might be associated with increased weight velocity. In summary, these data indicate that breastfeeding protects infants against infection with Giardia; provide no evidence of protection against repeat infections resulting from a prior infection and suggest but do not establish that a history of Giardia infection might be associated with decreased growth in young children. ^

Thrombolytic therapy for acute myocardial infarction: A cohort study to evaluate a selective approach to invasive diagnosis and therapy. The Corpus Christi Heart Project

Coronary perfusion with thrombolytic therapy and selective reperfusion by percutaneous transluminal coronary angioplasty (PTCA) were examined in the Corpus Christi Heart Project, a population-based surveillance program for hospitalized acute myocardial infarction (MI) patients in a biethnic community of Mexican-Americans (MAs) and non-Hispanic whites (NHWs). Results were based on 250 (12.4%) patients who received thromobolytic therapy in a cohort of 2011 acute MI cases. Out of these 107 (42.8%) underwent PTCA with a mean follow-up of 25 months. There were 186 (74.4%) men and 64 (25.6%) women; 148 (59.2%) were NHWs, 86 (34.4%) were MAs. Thrombolysis and PTCA were performed less frequently in women than in men, and less frequently in MAs than in NHWs.^ According to the coronary reperfusion interventions used, patients were divided in two groups, those that received no-PTCA (57.2%) and the other that underwent PTCA (42.8%) after thrombolysis. The case-fatality rate was higher in no-PTCA patients than in the PTCA (7.7% versus 5.6%), as was mortality at one year (16.2% versus 10.5%). Reperfusion was successful in 48.0% in the entire cohort and (51.4% versus 45.6%) in the PTCA and no-PTCA groups. Mortality in the successful reperfusion patients was 5.0% compared to 22.3% in the unsuccessful reperfusion group (p = 0.00016, 95% CI: 1.98-11.6).^ Cardiac catheterization was performed in 86.4% thrombolytic patients. Severe stenosis ($>$75%) obstruction was present most commonly in the left descending artery (52.8%) and in the right coronary artery (52.8%). The occurrence of adverse in-hospital clinical events was higher in the no-PTCA as compared to the PTCA and catheterized patients with the exception of reperfusion arrythmias (p = 0.140; Fisher's exact test p = 0.129).^ Cox regression analysis was used to study the relationship between selected variables and mortality. Apart from successful reperfusion, age group (p = 0.028, 95% CI: 2.1-12.42), site of acute MI index (p = 0.050) and ejection-fraction (p = 0.052) were predictors of long-term survival. The ejection-fraction in the PTCA group was higher than (median 78% versus 53%) in the no-PTCA group. Assessed by logistic regression analysis history of high cholesterol ($>$200mg/dl) and diabetes mellites did have significant prognostic value (p = 0.0233; p = 0.0318) in long-term survival irrespective of treatment status.^ In conclusion, the results of this study support the idea that the use of PTCA as a selective intervention following thrombolysis improves survival of patients with acute MI. The use of PTCA in this setting appears to be safe. However, we can not exclude the possibility that some of these results may have occurred due to the exclusion from PTCA of high risk patients (selection bias). ^

AN EPIDEMIOLOGIC DESCRIPTION AND ANALYSIS OF LOST WORKDAY OCCUPATIONAL BURN INJURIES

Background research consisted of a hospital case series of all adult burn patients (n = 162) admitted to John Sealy Hospital's burn unit from January 1978 to June 1979. Comparisons between occupationally and nonoccupationally burned adults demonstrated that occupationally burned adults were significantly more likely to have been active in the burn injury event and to have changed jobs during the prior year. They were significantly less likely to have physical or mental problems which contributed to sustaining the burn injury. Comparisons between occupational and nonoccupational burn injury events concluded that occupational burn injury events were significantly more likely to involve multiple sources of energy, sparks as the source of ignition and gases as the source of combustion. Other salient characteristics of occupational burn injuries indicated that subsequent research should focus upon lost workday occupational burns and other injuries sustained by blue-collar petrochemical workers employed in Galveston County, Texas.^ Subsequent research consisted of a historical cohort study of occupational injuries sustained in 1979 by a cohort of blue-collar petrochemical workers (n = 1771) who belonged to O.C.A.W. Local 4-449 in Texas City, Texas. Specific cohort injury rates included 15.08 occupational injuries per 100 person work-years, 11.98 lost workday occupational injuries per 100 person work-years, and 1.64 lost workday occupational burn injuries per 100 person work-years. Salient results from this study indicate that burn injuries are a very important type (in terms of both frequency and severity) of occupational injury sustained by blue-collar petrochemical workers, pipefitters are at greatest risk of lost workday injuries and lost workday burn injuries, company-specific experiences are comparable for lost workday occupational injuries, differences among company-specific nonlost workday occupational injury experiences may not be "safety-related", and minimal job-specific experience may not place employees at greater risk of lost workday burn injuries.^

REGRESSION ANALYSIS FOR STANDARDIZED MORTALITY RATIOS WITH APPLICATION TO OCCUPATIONAL FOLLOW-UP STUDIES

Traditional comparison of standardized mortality ratios (SMRs) can be misleading if the age-specific mortality ratios are not homogeneous. For this reason, a regression model has been developed which incorporates the mortality ratio as a function of age. This model is then applied to mortality data from an occupational cohort study. The nature of the occupational data necessitates the investigation of mortality ratios which increase with age. These occupational data are used primarily to illustrate and develop the statistical methodology.^ The age-specific mortality ratio (MR) for the covariates of interest can be written as MR(,ij...m) = ((mu)(,ij...m)/(theta)(,ij...m)) = r(.)exp (Z('')(,ij...m)(beta)) where (mu)(,ij...m) and (theta)(,ij...m) denote the force of mortality in the study and chosen standard populations in the ij...m('th) stratum, respectively, r is the intercept, Z(,ij...m) is the vector of covariables associated with the i('th) age interval, and (beta) is a vector of regression coefficients associated with these covariables. A Newton-Raphson iterative procedure has been used for determining the maximum likelihood estimates of the regression coefficients.^ This model provides a statistical method for a logical and easily interpretable explanation of an occupational cohort mortality experience. Since it gives a reasonable fit to the mortality data, it can also be concluded that the model is fairly realistic. The traditional statistical method for the analysis of occupational cohort mortality data is to present a summary index such as the SMR under the assumption of constant (homogeneous) age-specific mortality ratios. Since the mortality ratios for occupational groups usually increase with age, the homogeneity assumption of the age-specific mortality ratios is often untenable. The traditional method of comparing SMRs under the homogeneity assumption is a special case of this model, without age as a covariate.^ This model also provides a statistical technique to evaluate the relative risk between two SMRs or a dose-response relationship among several SMRs. The model presented has application in the medical, demographic and epidemiologic areas. The methods developed in this thesis are suitable for future analyses of mortality or morbidity data when the age-specific mortality/morbidity experience is a function of age or when there is an interaction effect between confounding variables needs to be evaluated. ^

A screening for anti-West Nile immunoglobulin-G and immunoglobulin-M in the Cameron County Hispanic cohort

This study is designed to be a cross-sectional, retrospective analysis of the seroprevalence of anti-WNV antibodies in 1,006 plasma samples collected from February 2, 2006 to June 18, 2007 originally for The Cameron County Hispanic Cohort: Extreme obesity and uncontrolled diabetes on the U.S.-Mexico border, major concerns for populations with health disparities. The aim of this thesis research is to give a more up-to-date picture of Flavivirus activity in south Texas, which can potentially contribute to the surveillance objective of arboviral control in this area. A West Nile virus (WNV) seroprevalence study in humans in this particular area has never before been completed. Plasma samples were tested using immunoglobulin-G (IgG) and immunoglobulin-M (IgM) WNV enzyme linked immunosorbent assays (ELISA). Estimated seroprevalence for this particular population was 0.98% or 9.8 cases of West Nile disease per 1,000 citizens. After IgG testing, seroprevalence in the study population was found to be 15.4%. Specimens tested for WNV IgG were compared with a subset of specimens (N=803) tested for history of primary dengue virus (DENV) infection. Of the 803 specimens tested for IgG to DENV, 308 were positive. Of the 132 positive WNV IgG specimens in the subset, 131 (99.2%) tested also tested positive for DENV IgG. It would be helpful to use standard plaque reduction neutralization testing to determine if the seroprevalence is in fact lower because of cross-reaction to DENV on testing. Regardless of the possibility of other Flavivirus activity occurring prior to the introduction of WNV into the United States and the potential for cross-reactivity, Texas has ranked in the top 5 states with the highest, laboratory confirmed incidence of infection with WNV since 2003. Indicating that climate factors and the presence of suitable vectors makes Texas a hotspot for WNV activity. ^ A description of the study population by age, gender, and income was done indicating a statistically significant income difference with a mean household income per year being $13,413.55 for a case and $20,268.80 for non-cases (p=0.001). Lower income neighborhoods should be targeted for education and prevention of vector-borne diseases during the summer months in Cameron County. With respect to gender, being male has been noted in the literature to be a risk factor for infection with WNV (25). In this study, females comprised approximately 68% of the study population, they also made up 66.5% of the positive IgG specimens. An odds ratio of 0.91 indicates that women are less likely to be IgG positive for WNV as compared to men; however, this was not found to be significant based on the 95% confidence interval, but is consistent with the literature. When looking at age difference between positive and negative/equivocal cases, there was no statistical difference found between the two groups. ^ We concluded that this study will enable us to understand the epidemiology of WNV transmission since its introduction into the United States and hopefully to maintain or improve the current measures we have in place to prevent infections that are seen annually with WNV.^

Longitudinal and logistic analysis of endocrine hormone profiles, physical maturation, and candidate genes related to pubertal events in children

Children who experience early pubertal development have an increased risk of developing cancer (breast, ovarian, and testicular), osteoporosis, insulin resistance, and obesity as adults. Early pubertal development has been associated with depression, aggressiveness, and increased sexual prowess. Possible explanations for the decline in age of pubertal onset include genetics, exposure to environmental toxins, better nutrition, and a reduction in childhood infections. In this study we (1) evaluated the association between 415 single nucleotide polymorphisms (SNPs) from hormonal pathways and early puberty, defined as menarche prior to age 12 in females and Tanner Stage 2 development prior to age 11 in males, and (2) measured endocrine hormone trajectories (estradiol, testosterone, and DHEAS) in relation to age, race, and Tanner Stage in a cohort of children from Project HeartBeat! At the end of the 4-year study, 193 females had onset of menarche and 121 males had pubertal staging at age 11. African American females had a younger mean age at menarche than Non-Hispanic White females. African American females and males had a lower mean age at each pubertal stage (1-5) than Non-Hispanic White females and males. African American females had higher mean BMI measures at each pubertal stage than Non-Hispanic White females. Of the 415 SNPs evaluated in females, 22 SNPs were associated with early menarche, when adjusted for race ( p<0.05), but none remained significant after adjusting for multiple testing by False Discovery Rate (p<0.00017). In males, 17 SNPs were associated with early pubertal development when adjusted for race (p<0.05), but none remained significant when adjusted for multiple testing (p<0.00017). ^ There were 4955 hormone measurements taken during the 4-year study period from 632 African American and Non-Hispanic White males and females. On average, African American females started and ended the pubertal process at a younger age than Non-Hispanic White females. The mean age of Tanner Stage 2 breast development in African American and Non-Hispanic White females was 9.7 (S.D.=0.8) and 10.2 (S.D.=1.1) years, respectively. There was a significant difference by race in mean age for each pubertal stage, except Tanner Stage 1 for pubic hair development. Both Estradiol and DHEAS levels in females varied significantly with age, but not by race. Estradiol and DHEAS levels increased from Tanner Stage 1 to Tanner Stage 5.^ African American males had a lower mean age at each Tanner Stage of development than Non-Hispanic White males. The mean age of Tanner Stage 2 genital development in African American and Non-Hispanic White males was 10.5 (S.D.=1.1) and 10.8 (S.D.=1.1) years, respectively, but this difference was not significant (p=0.11). Testosterone levels varied significantly with age and race. Non-Hispanic White males had higher levels of testosterone than African American males from Tanner Stage 1-4. Testosterone levels increased for both races from Tanner Stage 1 to Tanner Stage 5. Testosterone levels had the steepest increase from ages 11-15 for both races. DHEAS levels in males varied significantly with age, but not by race. DHEAS levels had the steepest increase from ages 14-17. ^ In conclusion, African American males and females experience pubertal onset at a younger age than Non-Hispanic White males and females, but in this study, we could not find a specific gene that explained the observed variation in age of pubertal onset. Future studies with larger study populations may provide a better understanding of the contribution of genes in early pubertal onset.^

A cross-sectional analysis of the association between polycyclic aromatic hydrocarbons and diesel particulate matter exposures and hypertension among individuals of Mexican origin residing in Houston, TX

Background. Research has shown that elevations of only 10 mmHg diastolic blood pressure (BP) and 5 mmHg systolic BP are associated with substantial (as large as 50%) increases in risks for cardiovascular disease, a leading cause of death, worldwide. Epidemiological studies have found that particulate matter (PM) increases blood pressure (BP) and many biological mechanisms which may suggest that the organic matter of PM contributes to the increase in BP. To understand components of PM which may contribute to the increase in BP, this study focuses on diesel particulate matter (DPM) and polycyclic aromatic hydrocarbons (PAHs). To our knowledge, there have been only four epidemiological studies on BP and DPM, and no epidemiological studies on BP and PAHs. ^ Objective. Our objective was to evaluate the association between prevalent hypertension and two ambient exposures: DPM and PAHs amongst the Mano a Mano cohort. ^ Methods. The Mano a Mano cohort which was established by the M.D. Anderson Cancer Center in 2001, is comprised of individuals of Mexican origin residing in Houston, TX. Using geographical information systems, we linked modeled annual estimates of PAHs and DPM at the census track level from the U.S. Environmental Protection Agency's National-Scale Air Toxics Assessment to residential addresses of cohort members. Mixed-effects logistic regression models were applied to determine associations between DPM and PAHs and hypertension while adjusting for confounders. ^ Results. Ambient levels of DPM, categorized into quartiles, were not statistically associated with hypertension and did not indicate a dose response relationship. Ambient levels of PAHs, categorized into quartiles, were not associated with hypertension, but did indicate a dose response relationship in multiple models (for example: Q2: OR = 0.98; 95% CI, 0.73–1.31, Q3: OR = 1.08; 95% CI, 0.82–1.41, Q4: OR = 1.26; 95% CI, 0.94–1.70). ^ Conclusion. This is the first assessment to analyze the relationship between ambient levels of PAHs and hypertension and it is amongst a few studies investigating the association between ambient levels of DPM and hypertension. Future analyses are warranted to explore the effects DPM and PAHs using different categorizations in order to clarify their relationships with hypertension.^

A systematic review and analysis of the association between endometriosis and ovarian cancer

Ovarian cancer is the most lethal of the gynecologic malignancies. The development of endometriosis has been shown to increase one's risk of ovarian cancer. Numerous studies have investigated this association, yet none have synthesized the available data. In a pooled analysis of cohort and case-control studies, the association between endometriosis and ovarian cancer was strengthened. Women who developed endometriosis-associated ovarian cancer were more likely to develop an early stage clear cell or endometrioid ovarian cancer histotypes and were more likely to have a better overall prognosis. The prognostic differences between endometriosis-associated ovarian cancer and ovarian cancer without an associated endometriosis may indicate genetic and environmental differences between groups.^

Is H. pylori infection associated with diarrhea in a cohort of 3- to 8-year-old Colombian children?

The Estudio Comunitario sobre la Salud del Niño cohort study followed 326 3- to 8-year-old Colombian children for 4 years to observe the natural history of Helicobacter pylori infection and identify risk factors for acquisition, recurrence and persistence. Acute H. pylori infection during childhood may predispose to other enteric infections and therefore increase the risk of diarrheal disease. This dissertation aimed to estimate the effect of H. pylori infection on the occurrence of diarrhea and parasitic co-infections. The analysis used Generalized Estimating Equations to obtain odds ratios to estimate relative risks for diarrhea and the Zhang-Yu algorithm to estimate relative risks for on parasitic infections. Andersen-Gill models were used to estimate rate ratios for the effect of H. pylori status on the recurrence of parasitic infections. H. pylori status was classified for the entire follow-up duration in 1 of 3 categories: persistently positive, intermittently positive, and persistently negative. Multivariable models included child’s sex, age, symptoms, medication use, and socio-environmental factors. H. pylori infection was weakly and imprecisely associated with diarrheal disease, which occurred at an unexpectedly low frequency in this study. Persistently H. pylori-positive children had a somewhat higher incidence of reported diarrhea than intermittently positive or persistently negative children. Stratified analysis revealed that the presence of specific helminthes modified the effect of persistent H. pylori infection on diarrhea. The incidence of any parasitic infections was higher in children with persistent H. pylori infection relative to those with intermittent or persistently negative status, but this association did not hold when adjusted for the full set of selected covariates. The effects of H. pylori persistent status were similar for the occurrence or recurrence of Giardia duodenalis, Entamoeba histolytica, and Ascaris lumbricoides. These results show that H. pylori frequently co-exists with other parasites in Andean children and suggest that intermittently H. pylori–positive children might be at a lower risk of parasitic infections than persistently positive children. The relationship of H. pylori infection, helminthic infection and diarrheal disease should be further explored in studies that devote more intensive resources to accurate ascertainment of diarrhea.^

Nonlinear dimension reduction in pathway-based genome-wide association analysis

Pathway based genome wide association study evolves from pathway analysis for microarray gene expression and is under rapid development as a complementary for single-SNP based genome wide association study. However, it faces new challenges, such as the summarization of SNP statistics to pathway statistics. The current study applies the ridge regularized Kernel Sliced Inverse Regression (KSIR) to achieve dimension reduction and compared this method to the other two widely used methods, the minimal-p-value (minP) approach of assigning the best test statistics of all SNPs in each pathway as the statistics of the pathway and the principal component analysis (PCA) method of utilizing PCA to calculate the principal components of each pathway. Comparison of the three methods using simulated datasets consisting of 500 cases, 500 controls and100 SNPs demonstrated that KSIR method outperformed the other two methods in terms of causal pathway ranking and the statistical power. PCA method showed similar performance as the minP method. KSIR method also showed a better performance over the other two methods in analyzing a real dataset, the WTCCC Ulcerative Colitis dataset consisting of 1762 cases, 3773 controls as the discovery cohort and 591 cases, 1639 controls as the replication cohort. Several immune and non-immune pathways relevant to ulcerative colitis were identified by these methods. Results from the current study provided a reference for further methodology development and identified novel pathways that may be of importance to the development of ulcerative colitis.^