Behavior Problems of Maltreated Children Receiving In-Home Child Welfare Services

This study evaluates the level of behavior problems in a previously little studied group—children with founded cases of abuse and neglect receiving child welfare services in their own homes. A sample of 149 maltreated children, living at home, were evaluated on the CBCL as they entered a service program to which they were referred by a large public child protective service system. These children were found to have elevated levels of behavior problems, with 43.6% scoring in the problematic range, a rate similar to children entering foster care. Practice and policy implications of these findings are discussed and highlighted.

Analysis of recurrent failure times: A time-dependent Yule process approach

Analysis of recurrent events has been widely discussed in medical, health services, insurance, and engineering areas in recent years. This research proposes to use a nonhomogeneous Yule process with the proportional intensity assumption to model the hazard function on recurrent events data and the associated risk factors. This method assumes that repeated events occur for each individual, with given covariates, according to a nonhomogeneous Yule process with intensity function λx(t) = λ 0(t) · exp( x′β). One of the advantages of using a non-homogeneous Yule process for recurrent events is that it assumes that the recurrent rate is proportional to the number of events that occur up to time t. Maximum likelihood estimation is used to provide estimates of the parameters in the model, and a generalized scoring iterative procedure is applied in numerical computation. ^ Model comparisons between the proposed method and other existing recurrent models are addressed by simulation. One example concerning recurrent myocardial infarction events compared between two distinct populations, Mexican-American and Non-Hispanic Whites in the Corpus Christi Heart Project is examined. ^

Risk Index Score (RISc)

The main objective of this study was to develop and validate a computer-based statistical algorithm based on a multivariable logistic model that can be translated into a simple scoring system in order to ascertain stroke cases using hospital admission medical records data. This algorithm, the Risk Index Score (RISc), was developed using data collected prospectively by the Brain Attack Surveillance in Corpus Christ (BASIC) project. The validity of the RISc was evaluated by estimating the concordance of scoring system stroke ascertainment to stroke ascertainment accomplished by physician review of hospital admission records. The goal of this study was to develop a rapid, simple, efficient, and accurate method to ascertain the incidence of stroke from routine hospital admission hospital admission records for epidemiologic investigations. ^ The main objectives of this study were to develop and validate a computer-based statistical algorithm based on a multivariable logistic model that could be translated into a simple scoring system to ascertain stroke cases using hospital admission medical records data. (Abstract shortened by UMI.)^

Evaluation of the city of Houston HIV/STD prevention program in Houston Independent School District (HISD) high schools

This cross-sectional study was undertaken to evaluate the impact in terms of HIV/STD knowledge and sexual behavior that the City of Houston HIV/STD prevention program in HISD high schools has had on students who have participated in it by comparing them with their peers who have not, based on self reports. The study further evaluated the program cost-effectiveness for averting future HIV infections by computing Cost-Utility Ratios based on reported sexual behavior. ^ Mixed results were obtained, indicating a statistically significant difference in knowledge with the intervention group having scored higher (p-value 0.001) but not for any of the behaviors assessed. The knowledge score outcome's overall p-value after adjusting for each stratifying variable (age, grade, gender and ethnicity) was statistically significant. The Odds Ratio of intervention group participants aged 15 years or more scoring 70% or higher was 1.86 times; that of intervention group female participants was 2.29 times; and that of intervention group Black/African American participants was 2.47 times relative to their comparison group counterparts. The knowledge score results remained statistically significant in the logistic regression model, which controlled for age, grade level, gender and ethnicity. The Odds Ratio in this case was 1.74. ^ Three scenarios based on the difference in the risk of HIV infection between the intervention and comparison group were used for computation of Cost-Utility Ratios: Base, worst and best-case scenario. The best-case scenario yielded cost-effective results for male participants and cost-saving results for female participants when using ethnicity-adjusted HIV prevalence. The scenario remained cost-effective for female participants when using the unadjusted HIV prevalence. ^ The challenge to the program is to devise approaches that can enhance benefits for male participants. If it is a threshold problem implying that male participants require more intensive programs for behavioral change, then programs should first be piloted among boys before being implemented across the board. If it is a reflection of gender differences, then we might have to go back to the drawing board and engage boys in focus group discussions that will help formulate more effective programs. Gender-blind approaches currently in vogue do not seem to be working. ^

Preclinical modeling of multi-drug cancer therapies

Anticancer drugs typically are administered in the clinic in the form of mixtures, sometimes called combinations. Only in rare cases, however, are mixtures approved as drugs. Rather, research on mixtures tends to occur after single drugs have been approved. The goal of this research project was to develop modeling approaches that would encourage rational preclinical mixture design. To this end, a series of models were developed. First, several QSAR classification models were constructed to predict the cytotoxicity, oral clearance, and acute systemic toxicity of drugs. The QSAR models were applied to a set of over 115,000 natural compounds in order to identify promising ones for testing in mixtures. Second, an improved method was developed to assess synergistic, antagonistic, and additive effects between drugs in a mixture. This method, dubbed the MixLow method, is similar to the Median-Effect method, the de facto standard for assessing drug interactions. The primary difference between the two is that the MixLow method uses a nonlinear mixed-effects model to estimate parameters of concentration-effect curves, rather than an ordinary least squares procedure. Parameter estimators produced by the MixLow method were more precise than those produced by the Median-Effect Method, and coverage of Loewe index confidence intervals was superior. Third, a model was developed to predict drug interactions based on scores obtained from virtual docking experiments. This represents a novel approach for modeling drug mixtures and was more useful for the data modeled here than competing approaches. The model was applied to cytotoxicity data for 45 mixtures, each composed of up to 10 selected drugs. One drug, doxorubicin, was a standard chemotherapy agent and the others were well-known natural compounds including curcumin, EGCG, quercetin, and rhein. Predictions of synergism/antagonism were made for all possible fixed-ratio mixtures, cytotoxicities of the 10 best-scoring mixtures were tested, and drug interactions were assessed. Predicted and observed responses were highly correlated (r2 = 0.83). Results suggested that some mixtures allowed up to an 11-fold reduction of doxorubicin concentrations without sacrificing efficacy. Taken together, the models developed in this project present a general approach to rational design of mixtures during preclinical drug development. ^

Breastfeeding the very preterm hospitalized infant: An ethnographic study

Purpose. To develop a greater understanding of the experience—including the thoughts, feelings, and actions—of mothers' initiation and maintenance of lactation within the context of the NICU following the birth of a very preterm infant. ^ Design. Mixed method with dominant focused ethnographic approach. Setting: A 76-bed neonatal intensive care unit in the largest children's hospital located in a large metropolitan city in southeast Texas. ^ Sample. Purposeful sampling resulted in 23 interviews with 14 subjects. ^ Methods. Mixed method design with a dominant qualitative approach combined with a quantitative component to further identify and expand upon the investigation of the population in question. Open-ended semi-structured interviews and fieldwork were used to explore the experience of breastfeeding in the context of the NICU for mothers of very preterm infants. Longitudinal data obtained from each subject included in-depth interviews, demographic and clinical information, milk expression patterns (including pumping frequency, duration, and milk volumes obtained), and scores obtained from the Edinburgh Postpartum Depression Scale (EPDS). ^ Findings. Thematic analysis revealed that mothers of very preterm infants experienced an interruption in the process of becoming a mother, a paradoxical experience related to aspects of their milk expression routines and patterns, and negotiating the NICU environment. Sub-themes of becoming a mother-interrupted included: attribution, separation, connection, and navigation. Additional sub-themes related to the paradoxical experience included: the pump sometimes acting as a wedge or link to the infant; diversionary thoughts/activities during pumping; and perceptions of milk flow/volume. The process of negotiation included the environment, adaptive/maladaptive strategies related to milk expression, motivating factors related to the provision of breast milk, and learning their infant's feeding cues/abilities. EPDS scores did not reveal congruent differences in those mothers scoring high compared to those scoring low. ^ Conclusions. Understanding the experiences of the mothers in this study allows for a better perspective of breastfeeding the very preterm infant in the context of the NICU. Findings from this study validate the difficult and incremental process of attaining maternal identity and the significant burden placed on these women with regards to the provision of breast milk and breastfeeding during their infant's hospitalization. ^

The School Sealant Program: An evaluation of the oral health education component

Dental caries is a common preventable childhood disease leading to severe physical, mental and economic repercussions for children and their families if left untreated. A needs assessment in Harris County reported that 45.9% of second graders had untreated dental caries. In order to address this growing problem, the School Sealant Program (SSP), a primary preventive initiative, was launched by the Houston Department of Health and Human Services (HDHHS) to provide oral health education, and underutilized dental preventive services to second grade children from participating Local School Districts (LSDs). ^ To determine the effectiveness and efficiency of the SSP, a program evaluation was conducted by the HDHHS between September 2007 and June 2008 for the Oral Health Education (OHE) component of the SSP. The objective of the evaluation was to assess short term changes in oral health knowledge of the participants and determine if these changes, if any, were due to the OHE sessions. An 8-item multiple choice pre/post test was developed for this purpose and administered to the participants before and immediately after the OHE sessions. ^ The present project analyzed pre and post test data of 1,088 second graders from 22 participating schools. Changes in overall and topic-specific knowledge of the program participants before and after the OHE sessions were analyzed using the Wilcoxon's signed rank test. ^ Results. The overall knowledge assessment showed a statistically significant (p <0.001) increase in the dental health knowledge of the participants after the oral health education sessions. Participants in the higher scoring category (7-8 correct responses) increased from 9.5% at baseline to 60.8% after the education sessions. Overall knowledge increased in all school regions with the highest knowledge gains seen in the Central and South regions. Males and females had similar knowledge gains. Significant knowledge differences were also found for each of the topic specific categories (functions of teeth, healthy diet, healthy habits, dental sealants; p<0.001) indicating an increase in topic specific knowledge of the participants post-health education sessions. ^ Conclusions. The OHE sessions were successful in increasing the short term oral health knowledge of the participants. ^

Sibling relationships in the family of a child with a burn injury

Purpose. Understanding siblings' experiences after a major childhood burn injury was the purpose of this mixed method, qualitative dominant study. The following research questions guided this project: How do siblings describe the impact of a major childhood burn injury experience? How do sibling relationship factors of warmth/closeness, relative status/power, conflict, and rivalry further clarify their relationship and their experience after a major burn injury? ^ Methods. A mixed method, qualitative dominant, design was implemented to understand the sibling experiences in a family with a child suffering from a major burn injury. Informants were selected from patients with childhood burn injuries attending the reconstructive clinic at a Gulf coast children's specialty hospital. The qualitative portion used the life story method, a narrative process, to portray the long-term impact on sibling relationships. A "case" represents a family unit and could be composed of one or multiple family members. Participants from 22 cases (N = 40 participants) were interviewed. Interviews were conducted in person and via telephone. The quantitative portion, or the embedded part of this mixed method design, used the Sibling Relationship Questionnaire Revised (SRQ-R) to conduct an additional structured interview and acquire scoring data. It was postulated that the SRQ-R would provide another perspective on the sibling experience and expand the qualitative data analysis. Thematic analysis was implemented on the qualitative interview data including the qualitative data from the interviews structured on the SRQ-R. Additionally, scores on the SRQ-R were tabulated to further describe the cases. ^ Results. The overall thematic pattern for the sibling relationship in families having a child with a major burn injury was that of normalization. Areas of normalization as well as the process of adjustment were the major themes. Areas of normalization were found in play and other activities, in school and work, and in family relations with their siblings and their parents. The process of adjustment in the sibling relationship was described as varied, involved school and work re-entry, and might even change their life perspective. Further analysis included an examination of the cases in which more than one person were interviewed and completed the SRQ-R. Participants from five ( n = 11) of six cases (n = 14), scored above 3.0 on the five-point scale on the Warmth/Closeness construct, indicating they perceived the sibling relationship as close. Five participants scored high on the Conflict construct and four participants scored high on the Rivalry construct. Finally, Relative Status/Power was low or negative in the six cases (n = 13). ^ Conclusions/implications. These findings suggest the importance of returning to normalcy for many of the families and the significance of sibling relationships on the process. Some of these families were able to use this major life event in a positive way to promote normalization. ^

Racial disparities in patient survival after liver transplantation in the United States

Background. Racial disparities in healthcare span such areas as access, outcomes after procedures, and patient satisfaction. Previous work suggested that minorities experience less healthcare and worse survival rates. In adult orthotopic liver transplantation (OLT) mixed results have been reported, with some showing African-American recipients having poor survival compared to Caucasians, and others finding no such discrepancy. ^ Purpose. This study’s purpose was to analyze the most recent United Network for Organ Sharing (UNOS) data, both before and after the implementation of the Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) scoring system, to determine if minority racial groups still experience poor outcomes after OLT. ^ Methods. The UNOS dataset for 1992-2001 (Era I) and 2002-2007 (Era II) was used. Patient survival rates for each Era and for adult and pediatric recipients were analyzed with adjustment. A separate multivariate analysis was performed on African-American adult patients in Era II in order to identify unique predictors for poor patient survival. ^ Results. The overall study included 66,118 OLT recipients. The majority were Caucasian (78%), followed by Hispanics (13%) and African-Americans (9%). Hispanic and African-American adults were more likely to be female, have Hepatitis C, to be in the intensive care unit (ICU) or ventilated at time of OLT, to have a MELD score ≥23, to have a lower education level, and to have public insurance when compared to Caucasian adults (all p-values < 0.05). Hispanic and African-American pediatric recipients were more likely have public insurance and less likely to receive a living donor OLT than were Caucasian pediatric OLT recipients (p <0.05). There was no difference in the likelihood of having a PELD score ≥21 among racial groups (p >0.40). African-American adults in Era I and Era II had worse patient survival rates than both Caucasians and Hispanic (pair-wise p-values <0.05). This same disparity was seen for pediatric recipients in Era I, but not in Era II. Multivariate analysis of African-American recipients revealed no unique predictors of patient death. ^ Conclusions. African-American race is still a predictor of poor outcome after adult OLT, even after adjustment for multiple clinical, demographic, and liver disease severity variables. Although African-American and Hispanic subgroups share many characteristics previously thought to increase risk of post-OLT death, only African-American patients have poor survival rates when compared to Caucasians. ^

Dietary patterns and risk of pancreatic cancer in a hospital-based case-control study

Background. It is important to understand the association between diet and risk of pancreatic cancer in order to better understand the etiology of pancreatic cancer.^ Objectives. Describe the dietary patterns of cases of adenocarcinoma of the pancreas and non-cancer controls and evaluate the odds of having a healthy eating pattern among cases and non-cancer controls.^ Design and Methods. An ongoing hospital-based case-control study was conducted in Houston, Texas from 2000-2008 with 678 pancreatic adenocarcinoma cases and 724 controls. Participants completed a food frequency questionnaire and a risk factor questionnaire. Dietary patterns were derived by principal component analysis and associations between dietary patterns and pancreatic cancer risk were assessed using unconditional logistic regression.^ Results. Two dietary patterns were derived: fruit-vegetable and high fat-meat. There were no statistically significant associations between the fruit-vegetable pattern and pancreatic cancer. An inverse association was seen between the high fat-meat pattern and pancreatic cancer risk when comparing those in the upper intake quintile to those scoring in the lowest quintile after adjusting for demographic and risk factor variables (OR=0.67, p=0.03). In sex-stratified analysis adjusted for demographic and risk factor variables, females scoring in the upper intake quintile of the fruit-vegetable pattern had a 49% lower risk of pancreatic cancer compared to females scoring in the lowest quintile (OR=0.51, p=0.03). An inverse relationship was also seen for the high fat-meat pattern when comparing females in the upper intake quintile to females in the lowest quintile (OR=0.50, p=0.03). In males, neither dietary pattern was significantly associated with pancreatic cancer.^ Conclusions. The current findings for the fruit-vegetable pattern are similar to those of previous studies and support the hypothesis that there is an inverse association between a “healthy” diet (comprised of fruits, vegetables, and whole grains) and risk of having pancreatic cancer (in females only). However, the inverse relationship with the high fat-meat pattern and risk of pancreatic cancer is contrary to other results. Further research on dietary patters and pancreatic cancer risk may lead to better understanding of the etiologic cause of pancreatic cancer.^

Nonpurging binge eaters versus nonbinge eaters and treatment retention for adult obesity

Dropout from obesity treatment has been a major factor associated with weight control failure, with few reliable predictors of dropouts or completers. Previous studies have tended to treat obese people as a homogeneous group with standard behavior modification-based interventions. Current research indicates there may be subgroups within the obese population, binge eaters and nonbinge eaters, who have different dropout rates. Current studies also recommend focusing on the subset of this subgroup that does not engage in purging (vomiting, laxative abuse, or excessive exercise) to compensate for binge eating. This research uses a secondary dataset (N = 156) from a prospective study in which participants were randomized to a Food Dependency (FD) and a Behavioral Self-Management (BSM) group for weight reduction. Criteria for subjects in the original study included (1) scoring higher on the existing Binge Eating Scale (BES) in order to ensure enrollment of more binge eaters and (2) no compensatory purging behavior for binge eating. Subjects were then reclassified in this study as binge eaters or nonbinge eaters using the more stringent proposed 1994 DSM-IV criteria for Binge Eating Disorder (BED). Subjects were followed for dropout. Variables studied were binge status, age at obesity onset, age at study baseline, class instructor, number of previous weight loss attempts, race, marital status, body mass index (BMI kg/m$\sp2$), type of intervention, work status, educational level, and social support. Stepwise backward regression Cox survival analysis indicated binge status had a consistent, statistically significant protective effect on dropout in which binge eaters were half as likely to dropout versus nonbinge eaters (p = 0.04). Cox proportional hazards analysis indicated no statistical difference in dropout by type of intervention (FD, p = 0.13; BSM, p = 0.80) when controlling for binge status. All other variables did not reach significance, which is consistent with the literature. Implications of these findings suggest that (1) the proposed 1994 DSM-IV criteria for BED is a more useful classification that the existing DSM-III-R criteria, and (2) the identification of subgroups among obese subjects is an important step in dropout and weight loss intervention research. Future research can confirm this finding. ^

The incidence of necrotizing changes in adults with pneumococcal pneumonia

Background. Necrotizing pneumonia is generally considered a rare complication of pneumococcal pneumonia in adults. We systematically studied the incidence of necrotizing changes in adult patients with pneumococcal pneumonia, and examined the severity of infection, the role of causative serotype and the association with bacteremia. ^ Methods. We used a data base of all pneumococcal infections identified at our medical center between 2000 and 2010. Original readings of chest X-rays (CXR) and computerized tomography (CT) were noted. All images were then reread independently by 2 radiologists. The severity of disease was assessed using the SMART-COP scoring system. ^ Results. There were 351 cases of pneumococcal pneumonia. Necrosis was reported in no original CXR readings and 6 of 136 (4.4%) CTs. With re-reading, 8 of 351 (2.3%) CXR and 15 of 136 (11.0%) CT had necrotizing changes. Overall, these changes were found in 23 of 351 (6.6%, 95% CI 4.0 - 9.1) patients. The incidence of bacteremia and the admitting SMART-COP scores were similar in patients with and without necrosis (P=1.00 and P=0.32, respectively). Type 3 pneumococcus was more commonly isolated from patients with than from patients without necrotizing pneumonia (P=0.05), but a total of 10 serotypes were identified among 16 cases in which the organism was available for typing. ^ Conclusions. Necrotizing changes in the lungs were seen in 6.6% (95% CI 4.0 - 9.1) of a large series of adults with pneumococcal pneumonia. Patients with necrosis were not more likely to have bacteremia or more severe disease. Type 3 pneumococcus was commonly implicated, but 9 other serotypes were also identified.^

Bayesian and survival model for tumor relapse status and disease-specific survival, with applications to breast cancer

Breast cancer is the most common non-skin cancer and the second leading cause of cancer-related death in women in the United States. Studies on ipsilateral breast tumor relapse (IBTR) status and disease-specific survival will help guide clinic treatment and predict patient prognosis.^ After breast conservation therapy, patients with breast cancer may experience breast tumor relapse. This relapse is classified into two distinct types: true local recurrence (TR) and new ipsilateral primary tumor (NP). However, the methods used to classify the relapse types are imperfect and are prone to misclassification. In addition, some observed survival data (e.g., time to relapse and time from relapse to death)are strongly correlated with relapse types. The first part of this dissertation presents a Bayesian approach to (1) modeling the potentially misclassified relapse status and the correlated survival information, (2) estimating the sensitivity and specificity of the diagnostic methods, and (3) quantify the covariate effects on event probabilities. A shared frailty was used to account for the within-subject correlation between survival times. The inference was conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in softwareWinBUGS. Simulation was used to validate the Bayesian method and assess its frequentist properties. The new model has two important innovations: (1) it utilizes the additional survival times correlated with the relapse status to improve the parameter estimation, and (2) it provides tools to address the correlation between the two diagnostic methods conditional to the true relapse types.^ Prediction of patients at highest risk for IBTR after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The goals of the second part of this dissertation were to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center, to determine the risk of IBTR in patients with DCIS treated with local excision, and to determine whether there is a subset of patients at low risk of IBTR. Patients who had undergone local excision from 1990 through 2007 at MD Anderson Cancer Center with a final diagnosis of DCIS (n=794) were included in this part. Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients with complete data. Nomogram for prediction of 5- and 10-year IBTR probabilities were found to demonstrate imperfect calibration and discrimination, with an area under the receiver operating characteristic curve of .63 and a concordance index of .63. In conclusion, predictive models for IBTR in DCIS patients treated with local excision are imperfect. Our current ability to accurately predict recurrence based on clinical parameters is limited.^ The American Joint Committee on Cancer (AJCC) staging of breast cancer is widely used to determine prognosis, yet survival within each AJCC stage shows wide variation and remains unpredictable. For the third part of this dissertation, biologic markers were hypothesized to be responsible for some of this variation, and the addition of biologic markers to current AJCC staging were examined for possibly provide improved prognostication. The initial cohort included patients treated with surgery as first intervention at MDACC from 1997 to 2006. Cox proportional hazards models were used to create prognostic scoring systems. AJCC pathologic staging parameters and biologic tumor markers were investigated to devise the scoring systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort to validate the scoring systems. Binary indicators for pathologic stage (PS), estrogen receptor status (E), and tumor grade (G) were summed to create PS+EG scoring systems devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups than the current AJCC staging system. The ability of the PS+EG score to stratify outcomes was confirmed in both internal and external validation cohorts. The current study proposes and validates a new staging system by incorporating tumor grade and ER status into current AJCC staging. We recommend that biologic markers be incorporating into revised versions of the AJCC staging system for patients receiving surgery as the first intervention.^ Chapter 1 focuses on developing a Bayesian method to solve misclassified relapse status and application to breast cancer data. Chapter 2 focuses on evaluation of a breast cancer nomogram for predicting risk of IBTR in patients with DCIS after local excision gives the statement of the problem in the clinical research. Chapter 3 focuses on validation of a novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention. ^

Functional Analysis of Drosophila Integrator Complex in snRNA 3' End Processing

Uridine-rich small nuclear RNAs (U snRNAs) play essential roles in eukaryotic gene expression by facilitating the removal of introns from mRNA precursors and the processing of the replication-dependent histone pre-mRNAs. Formation of the 3’ end of these snRNAs is carried out by a poorly characterized, twelve-membered protein complex named Integrator Complex. In the effort to understand Integrator Complex function in the formation of the snRNA 3’ end, we performed a functional RNAi screen in Drosophila S2 cells to identify protein factors required for snRNA 3’ end formation. This screen was conducted by using a fluorescence-based reporter that elicits GFP expression in response to a deficiency in snRNA processing. Besides scoring the known Integrator subunits, we identified Asunder and CG4785 as additional core members of the Integrator Complex. Additionally, we also found a conserved requirement for Cyclin C and Cdk8 in both fly and human snRNA 3’ end processing. We have further demonstrated that the kinase activity of Cdk8 is critical for snRNA 3’ end processing and is likely to function independent of its well-documented function within the Mediator Cdk8 module. Taken together, this work functionally defines the Drosophila Integrator Complex and demonstrates a novel function for Cyclin C/Cdk8 in snRNA 3’ end formation. This thesis work has also characterized an important functional interaction mediated by a microdomain within Integrator subunit 12 (IntS12) and IntS1 that is required for the activity of the Integrator Complex in processing the snRNA 3’ end. Through the development of a reporter-based functional RNAi-rescue assay in Drosophila S2 cells, we analyzed domains within IntS12 required for snRNA 3’ end formation. This analysis unexpectedly revealed that an N-terminal 30 amino acid region and not the highly conserved central PHD finger domain, is required for snRNA 3’ end cleavage. The IntS12 microdomain (1-45) functions autonomously, and is sufficient to interact and stabilize the putative scaffold protein IntS1. Our findings provide more details of the Integrator Complex for understanding the molecular mechanism of snRNA 3’ end processing. Moreover, these results lay the foundation for future studies of the complex through the identification of a novel functional domain within one subunit and the identification of additional subunits.

Baseline evaluation of environmental physical activity and nutrition support of Texas Medical Center hospital worksites

Background: Obesity is a major health problem in the United States that has reached epidemic proportions. With most U.S adults spending the majority of their waking hours at work, the influence of the workplace environment on obesity is gaining in importance. Recent research implicates worksites as providing an 'obesogenic' environment as they encourage overeating and reduce the opportunity for physical activity. Objective: The aim of this study is to describe the nutrition and physical activity environment of Texas Medical Center (TMC) hospitals participating in the Shape Up Houston evaluation study to develop a scoring system to quantify the environmental data collected using the Environmental Assessment Tool (EAT) survey and to assess the inter-observer reliability of using the EAT survey. Methods: A survey instrument that was adapted from the Environmental Assessment Tool (EAT) developed by Dejoy DM et al in 2008 to measure the hospital environmental support for nutrition and physical activity was used for this study. The inter-observer reliability of using the EAT survey was measured and total percent agreement scores were computed. Most responses on the EAT survey are dichotomous (Yes and No) and these responses were coded with a '0' for a 'no' response and a '1' for a 'yes' response. A summative scoring system was developed to quantify these responses. Each hospital was given a score for each scale and subscale on the EAT survey in addition to a total score. All analyses were conducted using Stata 11 software. Results: High inter-observer reliability is observed using EAT. The percentage agreement scores ranged from 94.4%–100%. Only 2 of the 5 hospitals had a fitness facility onsite and scores for exercise programs and outdoor facilities available for hospital employees ranged from 0–62% and 0–37.5%, respectively. The healthy eating percentage for hospital cafeterias range from 42%–92% across the different hospitals while the healthy vending scores were 0%–40%. The total TMC 'healthy hospital' score was 49%. Conclusion: The EAT survey is a reliable instrument for measuring the physical activity and nutrition support environment of hospital worksites. The study results showed a large variability among the TMC hospitals in the existing physical activity and nutrition support environment. This study proposes cost effective policy changes that can increase environmental support to healthy eating and active living among TMC hospital employees.^