A study of the factors in the background of children from the same families who have been referred to a child guidance clinic

Thesis (M.S.)--Boston University, 1946. This item was digitized by the Internet Archive

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

BACKGROUND: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. METHODS: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. RESULTS: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. CONCLUSIONS: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Hepatoprotection via the IL-6/Stat3 pathway

Stat3 is a vital transcription factor that is activated downstream of the gp130 receptor, primarily via IL-6 signaling in adult liver. A new study demonstrates that Stat3 provides hepatoprotection against Fas-mediated apoptotic liver damage by two mechanisms: direct inactivation of caspases and reduction of reactive oxygen species

Assessing for Ovulation in Transmasculine Individuals on Testosterone: Implications for Unmet Need for Contraception in the Trans Community

Thesis (Master's)--University of Washington, 2019Importance: An estimated 1.4 million people in the United States identify as transgender or non-binary (TNB), signifying that their gender identity does not correspond with their assigned birth sex. Individuals assigned female at birth may seek gender-affirming hormone therapy with injectable testosterone. No studies have directly examined ovulatory function or contraceptive need in transmasculine individuals on testosterone. Objective: Our objective was to determine whether testosterone reliably suppresses ovulation in transmasculine individuals, and to use this and existing data to perform an assessment of unmet need for contraception in this population. Methods: This is a observational prospective trial based at a community clinic serving over 400 patients annually for gender affirming hormone therapy. We enrolled individuals who were assigned female at birth and are currently using or seeking to initiate masculinizing therapy with testosterone (transmasculine individuals). Over a 12-week study period, subjects collected daily urine samples for pregnanediol-3-glucoronide (PdG) testing and completed daily electronic bleeding diaries. We collected monthly serum samples for mid-dosing interval serum testosterone, estradiol and sex-hormone binding globulin (SHBG) levels, and anti-mullerian hormone (AMH) values at baseline and study end. Ovulation was defined as PdG>5µg/mL for three consecutive days. We then used these data and the existing literature on fertility and family planning in this population to perform an assessment of unmet need for contraception. Main Outcomes and Measures: Our primary outcome was the proportion of participants who ovulated during the study period. Secondary outcomes included predictors of ovulation such as age, length of time on testosterone, serum testosterone levels, body mass infex (BMI), and bleeding pattern. Results: We enrolled 32 individuals and 20 completed the entire study. Median age was 23 (range 18-37). Six participants were new initiators of testosterone and 14 were continuing users. Among continuing users, median duration of testosterone therapy was 9 months (range 2-60 months). One participant-month of ovulation was observed using the standard criteria, however several other participants had transient rises in PdG followed by bleeding episodes suggestive of a dysfunctional ovulatory pattern. Significant research gaps exist in assessing for unmet need for contraception in the transmasculine population. Conclusions and Relevance: This study suggests that testosterone rapidly induces ovulatory dysfunction leading to eventual ovulatory suppression, though intermittent ovulations may be possible even in long-term users. Contraceptive need is largely unrecognized in this community, and more data are needed

Optimizing Student Satisfaction Measures Through Teacher Presence Interventions and Contextual Awareness in an Online Course

Faculty approaches successfully used in traditional classroom settings do not necessarily translate smoothly into online environments and new methods are required to be effective. In this paper we explore teacher presence in online environments. With online teacher presence less can be more and therefore must be consciously managed. Through the use of a single longitudinal case study, we track the evolution of an online MBA course from its initial offering through major revisions made to improve faculty performance. Changes to improve faculty presence are discussed and the importance of contextual factor considerations are propose