Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Models of DNA sequence evolution

Models of DNA sequence evolution and methods for estimating evolutionary distances are needed for studying the rate and pattern of molecular evolution and for inferring the evolutionary relationships of organisms or genes. In this dissertation, several new models and methods are developed.^ The rate variation among nucleotide sites: To obtain unbiased estimates of evolutionary distances, the rate heterogeneity among nucleotide sites of a gene should be considered. Commonly, it is assumed that the substitution rate varies among sites according to a gamma distribution (gamma model) or, more generally, an invariant+gamma model which includes some invariable sites. A maximum likelihood (ML) approach was developed for estimating the shape parameter of the gamma distribution $(\alpha)$ and/or the proportion of invariable sites $(\theta).$ Computer simulation showed that (1) under the gamma model, $\alpha$ can be well estimated from 3 or 4 sequences if the sequence length is long; and (2) the distance estimate is unbiased and robust against violations of the assumptions of the invariant+gamma model.^ However, this ML method requires a huge amount of computational time and is useful only for less than 6 sequences. Therefore, I developed a fast method for estimating $\alpha,$ which is easy to implement and requires no knowledge of tree. A computer program was developed for estimating $\alpha$ and evolutionary distances, which can handle the number of sequences as large as 30.^ Evolutionary distances under the stationary, time-reversible (SR) model: The SR model is a general model of nucleotide substitution, which assumes (i) stationary nucleotide frequencies and (ii) time-reversibility. It can be extended to SRV model which allows rate variation among sites. I developed a method for estimating the distance under the SR or SRV model, as well as the variance-covariance matrix of distances. Computer simulation showed that the SR method is better than a simpler method when the sequence length $L>1,000$ bp and is robust against deviations from time-reversibility. As expected, when the rate varies among sites, the SRV method is much better than the SR method.^ The evolutionary distances under nonstationary nucleotide frequencies: The statistical properties of the paralinear and LogDet distances under nonstationary nucleotide frequencies were studied. First, I developed formulas for correcting the estimation biases of the paralinear and LogDet distances. The performances of these formulas and the formulas for sampling variances were examined by computer simulation. Second, I developed a method for estimating the variance-covariance matrix of the paralinear distance, so that statistical tests of phylogenies can be conducted when the nucleotide frequencies are nonstationary. Third, a new method for testing the molecular clock hypothesis was developed in the nonstationary case. ^

Design and implementation of a multicriteria medical decision support system for diagnosis and treatment

Health care providers face the problem of trying to make decisions with inadequate information and also with an overload of (often contradictory) information. Physicians often choose treatment long before they know which disease is present. Indeed, uncertainty is intrinsic to the practice of medicine. Decision analysis can help physicians structure and work through a medical decision problem, and can provide reassurance that decisions are rational and consistent with the beliefs and preferences of other physicians and patients. ^ The primary purpose of this research project is to develop the theory, methods, techniques and tools necessary for designing and implementing a system to support solving medical decision problems. A case study involving “abdominal pain” serves as a prototype for implementing the system. The research, however, focuses on a generic class of problems and aims at covering theoretical as well as practical aspects of the system developed. ^ The main contributions of this research are: (1) bridging the gap between the statistical approach and the knowledge-based (expert) approach to medical decision making; (2) linking a collection of methods, techniques and tools together to allow for the design of a medical decision support system, based on a framework that involves the Analytic Network Process (ANP), the generalization of the Analytic Hierarchy Process (AHP) to dependence and feedback, for problems involving diagnosis and treatment; (3) enhancing the representation and manipulation of uncertainty in the ANP framework by incorporating group consensus weights; and (4) developing a computer program to assist in the implementation of the system. ^

Incidence of breast cancer in first-degree female relatives of men with newly diagnosed prostate cancer

Prostate cancer is the most common incident cancer and the second leading cause of death in men in the United States. Although numerous attempts have been made to identify risk factors associated with prostate cancer, the results have been inconsistent and conflicting. The only established risk factors are age and ethnicity. A positive family history of prostate cancer has also been shown to increase the risk two- to three-fold among close relatives.^ There are several similarities between breast and prostate cancer that make the relationship between the two of interest. (1) Histologically, both cancers are predominantly adenocarcinomas, (2) both organs have a sexual and/or reproductive role, (3) both cancers occur in hormone-responsive tissue, (4) therapy often consists of hormonal manipulation, (5) worldwide distribution patterns of prostate and breast cancer are positively correlated.^ A family history study was conducted to evaluate the aggregation of prostate cancer and co-aggregation of breast cancer in 149 patients referred to The University of Texas, M.D. Anderson Cancer Center with newly diagnosed prostate cancer. All patients were white, less than 75 years of age at diagnosis and permanent residents of the United States. Through a personal interview with the proband, family histories were collected on 1,128 first-degree relatives. Cancer diagnoses were verified through medical records or death certificate. Standardized incidence ratios were calculated using a computer program by Monson incorporating data from Connecticut Tumor Registry.^ In this study, familial aggregation of prostate cancer was verified only among the brothers, not among fathers. Although a statistically significant excess of breast cancer was not found, the increased point estimates in mothers, sisters and daughters are consistent with a co-aggregation hypothesis. Rather surprising was the finding of a seven-fold increased risk of prostate cancer and a three-fold increased risk of breast cancer among siblings in the presence of a maternal history of any cancer. Larger family history studies including high risk (African-Americans) and lower-risk groups (Hispanics) and incorporating molecular genetic evaluations should be conducted to determine if genetic differences play a role in the differential incidence rates across ethnic groups. ^

Spatial distribution of orofacial cleft birth defects and uranium-radium concentrations in tap water in Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala Counties, Texas

Background Past and recent evidence shows that radionuclides in drinking water may be a public health concern. Developmental thresholds for birth defects with respect to chronic low level domestic radiation exposures, such as through drinking water, have not been definitely recognized, and there is a strong need to address this deficiency in information. In this study we examined the geographic distribution of orofacial cleft birth defects in and around uranium mining district Counties in South Texas (Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala), from 1999 to 2007. The probable association of cleft birth defect rates by ZIP codes classified according to uranium and radium concentrations in drinking water supplies was evaluated. Similar associations between orofacial cleft birth defects and radium/radon in drinking water were reported earlier by Cech and co-investigators in another of the Gulf Coast region (Harris County, Texas).50, 55 Since substantial uranium mining activity existed and still exists in South Texas, contamination of drinking water sources with radiation and its relation to birth defects is a ground for concern. ^ Methods Residential addresses of orofacial cleft birth defect cases, as well as live births within the twenty Counties during 1999-2007 were geocoded and mapped. Prevalence rates were calculated by ZIP codes and were mapped accordingly. Locations of drinking water supplies were also geocoded and mapped. ZIP codes were stratified as having high combined uranium (≥30μg/L) vs. low combined uranium (<30μg/L). Likewise, ZIP codes having the uranium isotope, Ra-226 in drinking water, were also stratified as having elevated radium (≥3 pCi/L) vs. low radium (<3 pCi/L). A linear regression was performed using STATA® generalized linear model (GLM) program to evaluate the probable association between cleft birth defect rates by ZIP codes and concentration of uranium and radium via domestic water supply. These rates were further adjusted for potentially confounding variables such as maternal age, education, occupation, and ethnicity. ^ Results This study showed higher rates of cleft births in ZIP codes classified as having high combined uranium versus ZIP codes having low combined uranium. The model was further improved by adding radium stratified as explained above. Adjustment for maternal age and ethnicity did not substantially affect the statistical significance of uranium or radium concentrations in household water supplies. ^ Conclusion Although this study lacks individual exposure levels, the findings suggest a significant association between elevated uranium and radium concentrations in tap water and high orofacial birth defect rates by ZIP codes. Future case-control studies that can measure individual exposure levels and adjust for contending risk factors could result in a better understanding of the exposure-disease association.^

Evaluation and Model of a Clinical Librarian Program

Clinical medical librarianship is entering its second decade, but little evaluative data has accrued in the literature. Variations from the original programs and novel new approaches have insured the survival of the program so far. The clinical librarian (CL) forms a vital link between the library and the health care professional, operating as an important information transfer agent. However, to further insure the survival of these vital programs, hard evaluative evidence is needed. The University of Texas Medical Branch (UTMB) at Galveston began a CL Program in 1978/79. An extensive three-year pre/post evaluation study was conducted using a specifically developed evaluation model, which, if adopted by others, will provide the needed comparative data. Both a pilot study, or formative evaluation, and a summative evaluation were conducted. The results of this evaluation confirmed many of the conclusions reported by other CL programs. Eight hypotheses were proposed at the beginning of this study. Data were collected and used to support acceptance or rejection of the null hypotheses, and conclusions were drawn according to the results. Implications relevant to the study conclusions and future trends in medical librarianship are also discussed in the closing chapter.

A path analysis of an after-school health and exercise program for elementary school children in El Paso, Texas

As schools are pressured to perform on academics and standardized examinations, schools are reluctant to dedicate increased time to physical activity. After-school exercise and health programs may provide an opportunity to engage in more physical activity without taking time away from coursework during the day. The current study is a secondary data analysis of data from a randomized trial of a 10-week after-school program (six schools, n = 903) that implemented an exercise component based on the CATCH physical activity component and health modules based on the culturally-tailored Bienestar health education program. Outcome variables included BMI and aerobic capacity, health knowledge and healthy food intentions as assessed through path analysis techniques. Both the baseline model (χ2 (df = 8) = 16.90, p = .031; RMSEA = .035 (90% CI of .010–.058), NNFI = 0.983 and the CFI = 0.995) and the model incorporating intervention participation proved to be a good fit to the data (χ2 (df = 10) = 11.59, p = .314. RMSEA = .013 (90% CI of .010–.039); NNFI = 0.996 and CFI = 0.999). Experimental group participation was not predictive of changes in health knowledge, intentions to eat healthy foods or changes in Body Mass Index, but it was associated with increased aerobic capacity, β = .067, p < .05. School characteristics including SES and Language proficiency proved to be significantly associated with changes in knowledge and physical indicators. Further effects of school level variables on intervention outcomes are recommended so that tailored interventions can be developed aimed at the specific characteristics of each participating school. ^

Effects of a health advocacy program to promote physical activity and nutrition behaviors among adolescents: An evaluation of the Young Leaders for Healthy Change program

Background. This study was designed to evaluate the effects of the Young Leaders for Healthy Change program, an internet-delivered program in the school setting that emphasized health advocacy skills-development, on nutrition and physical activity behaviors among older adolescents (13–18 years). The program consisted of online curricular modules, training modules, social media, peer and parental support, and a community service project. Module content was developed based on Social Cognitive Theory and known determinants of behavior for older adolescents. ^ Methods. Of the 283 students who participated in the fall 2011 YL program, 38 students participated in at least ten of the 12 weeks and were eligible for this study. This study used a single group-only pretest/posttest evaluation design. Participants were 68% female, 58% white/Caucasian, 74% 10th or 11th graders, and 89% mostly A and/or B students. The primary behavioral outcomes for this analysis were participation in 60-minutes of physical activity per day, 20-minutes of vigorous- or moderate- intensity physical activity (MVPA) participation per day, television and computer time, fruit and vegetable (FV) intake, sugar-sweetened beverage intake, and consumption of breakfast, home-cooked meals, and fast food. Other outcomes included knowledge, beliefs, and attitudes related to healthy eating, physical activity, and advocacy skills. ^ Findings. Among the 38 participants, no significant changes in any variables were observed. However, among those who did not previously meet behavioral goals there was an 89% increase in students who participated in more than 20 minutes of MVPA per day and a 58% increase in students who ate home-cooked meals 5–7 days per week. The majority of participants met program goals related to knowledge, beliefs, and attitudes prior to the start of the program. Participants reported either maintaining or improving to the goal at posttest for all items except FV intake knowledge, taste and affordability of healthy foods, interest in teaching others about being healthy, and ease of finding ways to advocate in the community. ^ Conclusions. The results of this evaluation indicated that promoting healthy behaviors requires different strategies than maintaining healthy behaviors among high school students. In the school setting, programs need to target the promotion and maintenance of health behaviors to engage all students who participate in the program as part of a class or club activity. Tailoring the program using screening and modifying strategies to meet the needs of all students may increase the potential reach of the program. The Transtheoretical Model may provide information on how to develop a tailored program. Additional research on how to utilize the constructs of TTM effectively among high school students needs to be conducted. Further evaluation studies should employ a more expansive evaluation to assess the long-term effectiveness of health advocacy programming.^