Baseline Social Characteristics and Barriers to Care from a Special Projects of National Significance Women of Color with HIV Study: A Comparison of Urban and Rural Women and Barriers to HIV Care

We describe the baseline sociodemographic characteristics of the Health Resources and Services Administration's Special Programs of National Significance Women of Color (WOC) Initiative. Between November 2010 and July 2013, 921 WOC were prospectively enrolled in HIV medical care at nine sites, six urban (N=641) and three rural sites (N=280) across the US. We describe the study sample, drawing comparisons between urban and rural sites on sociodemographics, barriers to HIV care, HIV care status at study entry, substance use and sexual risk factors, and the relationship among these variables. Urban sites' participants differed from rural sites on all sociodemographic variables except age (median=42.3). Women at urban sites were more likely to be Hispanic, less educated, single, living alone, unstably housed, unemployed, and to have reported lower income. More urban women were transferring care to HIV care or had been lost to care. Urban women reported more barriers to care, many relating to stigma or fatalism about HIV care. Urban women reported more substance use and sexual risk behaviors. A better understanding of how HIV care is embedded in communities or fragmented across many sites in urban areas may help understand barriers to long-term engagement in HIV care encountered by WOC

Absence of Donor-Specific Anti-HLA Antibodies After ABO-Incompatible Heart Transplantation in Infancy: Altered Immunity or Age?

Specific B-cell tolerance toward donor blood group antigens develops in infants after ABO-incompatible heart transplantation, whereas their immune response toward protein antigens such as HLA has not been investigated. We assessed de novo HLA-antibodies in 122 patients after pediatric thoracic transplantation (28 ABO-incompatible) and 36 controls. Median age at transplantation was 1.7 years (1 day to 17.8 year) and samples were collected at median 3.48 years after transplantation. Antibodies were detected against HLA-class I in 21 patients (17.2%), class II in 18 (14.8%) and against both classes in 10 (8.2%). Using single-antigen beads, donor-specific antibodies (DSAs) were identified in six patients (all class II, one additional class I). Patients with DSAs were significantly older at time of transplantation. In patients who had undergone pretransplant cardiac surgeries, class II antibodies were more frequent, although use of homografts or mechanical heart support had no influence. DSAs were absent in ABO-incompatible recipients and class II antibodies were significantly less frequent than in children with ABO-compatible transplants. This difference was present also when comparing only children transplanted below 2 years of age. Therefore, tolerance toward the donor blood group appears to be associated with an altered response to HLA beyond age-related effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78721/1/j.1600-6143.2009.02877.x.pd

Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

Machine learning uncovers the most robust self-report predictors of relationship quality across 43 longitudinal couples studies

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner’s ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person’s own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships

Transcriptional Enhancers in Protein-Coding Exons of Vertebrate Developmental Genes

Many conserved noncoding sequences function as transcriptional enhancers that regulate gene expression. Here, we report that protein-coding DNA also frequently contains enhancers functioning at the transcriptional level. We tested the enhancer activity of 31 protein-coding exons, which we chose based on strong sequence conservation between zebrafish and human, and occurrence in developmental genes, using a Tol2 transposable GFP reporter assay in zebrafish. For each exon we measured GFP expression in hundreds of embryos in 10 anatomies via a novel system that implements the voice-recognition capabilities of a cellular phone. We find that 24/31 (77%) exons drive GFP expression compared to a minimal promoter control, and 14/24 are anatomy-specific (expression in four anatomies or less). GFP expression driven by these coding enhancers frequently overlaps the anatomies where the host gene is expressed (60%), suggesting self-regulation. Highly conserved coding sequences and highly conserved noncoding sequences do not significantly differ in enhancer activity (coding: 24/31 vs. noncoding: 105/147) or tissue-specificity (coding: 14/24 vs. noncoding: 50/105). Furthermore, coding and noncoding enhancers display similar levels of the enhancer-related histone modification H3K4me1 (coding: 9/24 vs noncoding: 34/81). Meanwhile, coding enhancers are over three times as likely to contain an H3K4me1 mark as other exons of the host gene. Our work suggests that developmental transcriptional enhancers do not discriminate between coding and noncoding DNA and reveals widespread dual functions in protein-coding DNA

Baseline Social Characteristics and Barriers to Care from a Special Projects of National Significance Women of Color with HIV Study: A Comparison of Urban and Rural Women and Barriers to HIV Care

We describe the baseline sociodemographic characteristics of the Health Resources and Services Administration's Special Programs of National Significance Women of Color (WOC) Initiative. Between November 2010 and July 2013, 921 WOC were prospectively enrolled in HIV medical care at nine sites, six urban (N=641) and three rural sites (N=280) across the US. We describe the study sample, drawing comparisons between urban and rural sites on sociodemographics, barriers to HIV care, HIV care status at study entry, substance use and sexual risk factors, and the relationship among these variables. Urban sites' participants differed from rural sites on all sociodemographic variables except age (median=42.3). Women at urban sites were more likely to be Hispanic, less educated, single, living alone, unstably housed, unemployed, and to have reported lower income. More urban women were transferring care to HIV care or had been lost to care. Urban women reported more barriers to care, many relating to stigma or fatalism about HIV care. Urban women reported more substance use and sexual risk behaviors. A better understanding of how HIV care is embedded in communities or fragmented across many sites in urban areas may help understand barriers to long-term engagement in HIV care encountered by WOC