Digital Commons Network^™

Identification Of An Association Of Tnfaip3 Polymorphisms With Matrix Metalloproteinase Expression In Fibroblasts In An Integrative Study Of Systemic Sclerosis-Associated Genetic And Environmental Factors.*, Peng Wei, Yang Yang, Xinjian Guo, Nainan Hei, Syeling Lai, Shervin Assassi, Mengyuan Liu, Filemon Tan, Xiaodong Zhou

Faculty Publications

OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.

METHODS: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis …

Is Whole-Exome Sequencing An Ethically Disruptive Technology? Perspectives Of Pediatric Oncologists And Parents Of Pediatric Patients With Solid Tumors., Laurence B Mccullough, Melody J Slashinski, Amy L Mcguire, Richard L Street, Christine M Eng, Richard A Gibbs, D William Parsons, Sharon E Plon

Faculty Publications

BACKGROUND: It has been anticipated that physician and parents will be ill prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive.

PROCEDURE: As a part of the Baylor Advancing Sequencing in Childhood Cancer Care study, we conducted semistructured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis …

Binomial Regression With A Misclassified Covariate And Outcome., Sheng Luo, Wenyaw Chan, Michelle A Detry, Paul J Massman, R S. Doody

Faculty Publications

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease-exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach …

Identification Of A Novel Gene On 10q22.1 Causing Autosomal Dominant Retinitis Pigmentosa (Adrp)., Stephen P Daiger, Lori S Sullivan, Sara J Bowne, Daniel C Koboldt, Susan H Blanton, Dianna K Wheaton, Cheryl E Avery, Elizabeth D Cadena, Robert K Koenekoop, Robert S Fulton, Richard K Wilson, George M Weinstock, Richard A Lewis, David G Birch

Faculty Publications

Whole-genome linkage mapping identified a region on chromosome 10q21.3-q22.1 with a maximum LOD score of 3.0 at 0 % recombination in a six-generation family with autosomal dominant retinitis pigmentosa (adRP). All known adRP genes and X-linked RP genes were excluded in the family by a combination of methods. Whole-exome next-generation sequencing revealed a missense mutation in hexokinase 1, HK1 c.2539G > A, p.Glu847Lys, tracking with disease in all affected family members. One severely-affected male is homozygous for this region by linkage analysis and has two copies of the mutation. No other potential mutations were detected in the linkage region nor were …

Emotional Climate, Feeding Practices, And Feeding Styles: An Observational Analysis Of The Dinner Meal In Head Start Families, Sheryl O Hughes, Thomas G Power, Maria A Papaioannou, Matthew B Cross, Theresa A Nicklas, Sharon K Hall, Richard M Shewchuk

Faculty Publications

BACKGROUND: A number of studies conducted with ethnically diverse, low-income samples have found that parents with indulgent feeding styles had children with a higher weight status. Indulgent parents are those who are responsive to their child's emotional states but have problems setting appropriate boundaries with their child. Because the processes through which styles impact child weight are poorly understood, the aim of this study was to observe differences in the emotional climate created by parents (including affect, tone of voice, and gestures) and behavioral feeding practices among those reporting different feeding styles on the Caregiver's Feeding Styles Questionnaire. A secondary …

Dissociation Predicts Later Attention Problems In Sexually Abused Children., Julie B Kaplow, Erin Hall, Karestan C Koenen, Kenneth A Dodge, Lisa Amaya-Jackson

Faculty Publications

OBJECTIVE: The goals of this research are to develop and test a prospective model of attention problems in sexually abused children that includes fixed variables (e.g., gender), trauma, and disclosure-related pathways.

METHODS: At Time 1, fixed variables, trauma variables, and stress reactions upon disclosure were assessed in 156 children aged 8-13 years. At the Time 2 follow-up (8-36 months following the initial interview), 56 of the children were assessed for attention problems.

RESULTS: A path analysis involving a series of hierarchically nested, ordinary least squares multiple regression analyses indicated two direct paths to attention problems including the child's relationship to …

Inducible Caspase 9 Suicide Gene To Improve The Safety Of Allodepleted T Cells After Haploidentical Stem Cell Transplantation., Siok-Keen Tey, Gianpietro Dotti, Cliona M. Rooney, Helen E. Heslop, Malcolm K. Brenner

Faculty Publications

Addback of donor T cells following T cell-depleted stem cell transplantation (SCT) can accelerate immune reconstitution and be effective against relapsed malignancy. After haploidentical SCT, a high risk of graft-versus-host disease (GVHD) essentially precludes this option, unless the T cells are first depleted of alloreactive precursor cells. Even then, the risks of severe GVHD remain significant. To increase the safety of the approach and thereby permit administration of larger T cell doses, we used a suicide gene, inducible caspase 9 (iCasp9), to transduce allodepleted T cells, permitting their destruction should administration have adverse effects. We made a retroviral vector encoding …

Making Minimally Invasive Thr Safe: Conclusions From Biomechanical Simulation And Analysis., P C. Noble, J D. Johnston, J A. Alexander, M T. Thompson, M M. Usrey, E M. Heinrich, G C. Landon, K B. Mathis

Faculty Publications

The use of smaller surgical incisions has become popularized for total hip arthroplasty (THR) because of the potential benefits of shorter recovery and improved cosmetic appearance. However, an increased incidence of serious complications has been reported. To minimize the risks of minimally invasive approaches to THR, we have developed an experimental approach which enables us to evaluate risk factors in these procedures through cadaveric simulations performed within the laboratory. During cadaveric hip replacement procedures performed via posterior and antero-lateral mini-incisions, pressures developed between the wound edges and the retractors were approximately double those recorded during conventional hip replacement using Charnley …

Ethnic/Racial Diversity, Maternal Stress, Lactation And Very Low Birthweight Infants., C Lau, N M. Hurst, E O. Smith, R J. Schanler

Faculty Publications

OBJECTIVE: (1) To compare maternal characteristics and psychological stress profile among African-American, Caucasian and Hispanic mothers who delivered very low birthweight infants. (2) To investigate associations between psychosocial factors, frequency of milk expression, skin-to-skin holding (STS), and lactation performance, defined as maternal drive to express milk and milk volume. STUDY DESIGN: Self-reported psychological questionnaires were given every 2 weeks after delivery over 10 weeks. Milk expression frequency, STS, and socioeconomic variables were collected. RESULT: Infant birthweight, education, and milk expression frequency differed between groups. Trait anxiety, depression and parental stress in a neonatal intensive care unit (PSS:NICU) were similar. African-American …

Treatment Of Solid Organ Transplant Recipients With Autologous Epstein Barr Virus-Specific Cytotoxic T Lymphocytes (Ctls)., Barbara Savoldo, John A. Goss, Markus M. Hammer, Lan Zhang, Teresita Lopez, Adrian P. Gee, Yu-Feng Lin, Ruben E. Quiros-Tejeira, Petra Reinke, Stephan Schubert, Stephen Gottschalk, Milton J. Finegold, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop

Faculty Publications

We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive …

Does The Choice Of Bottle Nipple Affect The Oral Feeding Performance Of Very-Low-Birthweight (Vlbw) Infants?, C E. Scheel, Richard J. Schanler, Chantal Lau

Faculty Publications

BACKGROUND: There is a continuous debate regarding the best bottle nipple to be used to enhance the bottle-feeding performance of a preterm infant. Aim: To verify that feeding performance can be improved by using the bottle nipple with the physical characteristics that enhance infants' sucking skills. METHODS: Ten "healthy" VLBW infants (941+/-273 g) were recruited. Feeding performance was monitored at two time periods, when taking 1-2 and 6-8 oral feedings/d. At each time and within 24 h, performance was monitored using three different bottle nipples offered in a randomized order. Rate of milk transfer (ml/min) was the primary outcome measure. …

Pathways To Ptsd, Part Ii: Sexually Abused Children., Julie B Kaplow, Kenneth A Dodge, Lisa Amaya-Jackson, Glenn N Saxe

Faculty Publications

OBJECTIVE: The goal of this research was to develop and test a prospective model of posttraumatic stress symptoms in sexually abused children that includes pretrauma, trauma, and disclosure-related pathways.

METHOD: At time 1, several measures were used to assess pretrauma variables, trauma variables, and stress reactions upon disclosure for 156 sexually abused children ages 8 to 13 years. At the time 2 follow-up (7 to 36 months following the initial interview), the children were assessed for posttraumatic stress disorder (PTSD) symptoms.

RESULTS: A path analysis involving a series of hierarchically nested ordinary least squares multiple regression analyses indicated three direct …

A 12-Year Prospective Study Of The Long-Term Effects Of Early Child Physical Maltreatment On Psychological, Behavioral, And Academic Problems In Adolescence., Jennifer E Lansford, Kenneth A Dodge, Gregory S Pettit, John E Bates, Joseph Crozier, Julie Kaplow

Faculty Publications

OBJECTIVE: To determine whether child physical maltreatment early in life has long-term effects on psychological, behavioral, and academic problems independent of other characteristics associated with maltreatment.

DESIGN: Prospective longitudinal study with data collected annually from 1987 through 1999.

SETTING AND PARTICIPANTS: Randomly selected, community-based samples of 585 children from the ongoing Child Development Project were recruited the summer before children entered kindergarten in 3 geographic sites. Seventy-nine percent continued to participate in grade 11. The initial in-home interviews revealed that 69 children (11.8%) had experienced physical maltreatment prior to kindergarten matriculation.

MAIN OUTCOME MEASURES: Adolescent assessment of school grades, standardized …

Child, Parent, And Peer Predictors Of Early-Onset Substance Use: A Multisite Longitudinal Study, Julie B Kaplow, Patrick J Curran, Kenneth A Dodge

Faculty Publications

The purpose of this study was to identify kindergarten-age predictors of early-onset substance use from demographic, environmental, parenting, child psychological, behavioral, and social functioning domains. Data from a longitudinal study of 295 children were gathered using multiple-assessment methods and multiple informants in kindergarten and 1st grade. Annual assessments at ages 10, 11, and 12 reflected that 21% of children reported having initiated substance use by age 12. Results from longitudinal logistic regression models indicated that risk factors at kindergarten include being male, having a parent who abused substances, lower levels of parental verbal reasoning, higher levels of overactivity, more thought …