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Delta Omega Abstracts

2015 Awardee Abstracts

Behavioral and Community Health Sciences

James E. Egan, PhD

Gays in the Neighborhood: How neighborhood and Context impact HIV and Substance use risks and resiliencies of gay, bisexual and other men who have sex with men in new york city

Thirty years into the HIV pandemic gay, bisexual, and other men who have sex with men (MSM) are still disproportionately impacted by HIV/AIDS, accounting for two-thirds of the U.S epidemic. There is increasing evidence that context is an important driver of HIV risk. This dissertation was designed to summarize the literature on the influences of neighborhoods on MSM health and to explore three contextual moments of heightened HIV risk using data from the NYCM2M study (N=1493). Migration: There is a well-established history of gay migration to NYC. These data support that migration is an important moment of heightened HIV risk for MSM. More recent migrants to NYC had increased risk for condomless sex and heavy drinking compared to men in NYC for longer. Compared to White MSM, Black and Latino MSM had a greater proportional hazard of seroconverting within the first ten years of migration. Community Viral Load (CVL): Where MSM live and have sex is not random, but constructed by socio-historical factors. These findings suggest that differences may be an important determinant in the social epidemiology of HIV. Compared to White MSM, Black MSM had greater odds of living in and having sex in higher CVL neighborhoods, Latino MSM had greater odds of a higher CVL sex neighborhood. Both Black MSM and bisexuals had greater odds of migrating to higher CVL spaces (than White gay men). White MSM who migrated had greater odds for condomless sex than those who did not. Substance Use: Elevated substance use has been documented among MSM, particularly those in cities. These findings show significant between neighborhood differences in any drug use and hazardous drinking (home and social) and heavy drinking (social) suggesting that neighborhood factors uniquely influence substance use behaviors among MSM. Without substantial changes to the implementation of HIV treatment/prevention, we will continue to fall short of our potential impact. Although context/place has considerable promise as a location for HIV prevention efforts, it has been underemphasized. This dissertation is a step towards addressing this gap, suggesting contextual opportunities for multi-level public health HIV interventions to reduce HIV among MSM.


Natalie Christine Ernecoff, MPH

Health Behavior Change in Advance Care Planning: An Agent-Based Model

Significance: A practical and ethical challenge in advance care planning research is controlling and intervening on human behavior. Additionally, observing dynamic changes in advance care planning (ACP) behavior proves difficult, though tracking changes over time is important for intervention development. Agent-based modeling (ABM) allows researchers to integrate complex behavioral data about advance care planning behaviors and thought processes into a controlled environment that is more easily alterable and observable. Literature to date has not addressed how best to motivate individuals, increase facilitators and reduce barriers associated with ACP. We aimed to build an ABM that accurately reflects: 1) the rates at which individuals complete the ACP process, 2) how individuals respond to barriers, facilitators, and behavioral variables 3) the interactions between these variables, 4) suggests -future -public health interventions and validation studies. Methods: We developed an ABM of the ACP -decision making process. We integrated into this dynamic model the barriers, facilitators, and other behavioral variables - that -agents encounter as they move- through the Transtheoretical Model’s stages of change. Findings: We successfully incorporated ACP barriers, facilitators, and other behavioral variables into our ABM, forming a plausible representation of ACP behavior and decision-making. In addition, the resulting distributions across the stages of change replicated those found in the literature, with approximately half of participants in the action-maintenance stage in both the model and the literature. Public Health Implications: Our ABM is the first of its kind to outline potential intervention points for behavior change in the context of ACP. The ABM approach to ACP is a useful method for representing dynamic social and experiential influences on the decision making process. This model could be used in the future to test structural interventions (e.g. increasing access to ACP materials in primary care clinics) theoretically before implementation. Future studies can expand on this by gathering longitudinal, individual-level data and integrating it into the ABM for a more comprehensive representation of decision-making patterns with respect to ACP.

Biostatistics

Qing Liu, PhD

Dynamic Prediction Models for Data with Competing Risks

Prediction of cause-specific cumulative incidence function (CIF) is of primary interest to clinical researchers when conducting statistical analysis involving competing risks. The predicted CIFs need to be dynamically updated by incorporating the time-dependent information measured during follow-up. However, dynamic prediction of the conditional CIFs requires simultaneously updating the overall survival and the CIF while adjusting for the time-dependent covariates and the time-varying covariate effects which is complex and challenging. In this study, we extended the landmark Cox models to data with competing risks, because the landmark Cox models provide a simple way to incorporate various types of time-dependent information for data without competing risks. The resulting new models are called landmark proportional subdistribution hazards (PSH) models. In this study, we first investigated the properties of the Fine-Gray model under non-PSH and proposed a robust risk prediction procedure which is not sensitive to the PSH assumption. Then, we developed a landmark PSH model and a more comprehensive landmark PSH supermodel. The performance of our models was assessed via simulations and through analysis of data from a multicenter clinical trial for breast cancer patients. As compared with other dynamic predictive models, our proposed models exhibited three advantages. First, our models are robust against violations of the PSH assumption and can directly predict the conditional CIFs bypassing the estimation of overall survival and greatly simplify the prediction procedure. Second, our landmark PSH supermodel enables users to make predictions with a set of landmark points in one step. Third, the proposed models can simply incorporate various types of time-varying information. Finally, our models are not computationally intensive and can be easily implemented with existing statistical software. Public Health Significance: Prognostic models for predicting the absolute risk of a patient in having a disease are very useful in performing risk stratification and making treatment decisions. Since the patient’s prognosis can change over time, it is necessary to update the risk prediction accordingly. The dynamic prediction models developed in this study can provide more accurate prognoses over the course of disease progression and will be helpful to physicians in adopting personalized treatment regimes.


Environmental and Occupational Health

Jessie L. Carr Shmool, DrPH

Exposure Assessment Methods for Examining the Role of Non-Chemical Stressors in Environmental Health Disparities

Increases in chronic diseases among children are cause for public health concern and action, particularly as children of color and low socioeconomic position are disproportionately impacted, with far-reaching consequences for health and well-being over the life-course. Environmental toxicants and non-chemical stressors have been linked with adverse health outcomes and disparities. Specifically, recent toxicological and epidemiological evidence suggests that chronic psychosocial stress may modify pollution effects on health. Thus, there is increasing interest in refined methods for assessing and incorporating non-chemical exposures, including social stressors, into environmental health research, towards identifying whether and how psychosocial stress interacts with chemical exposures to influence health and health disparities. The overall objective of this dissertation is to apply exposure science principles to develop and validate methods for non-chemical exposure assessment, toward examining differential susceptibility and disproportionate exposures in social-environmental epidemiology. To do so, I utilize a spatial approach to characterize intra-urban variation in and correlation among social stressors, socioeconomic position, and air pollution exposures across New York City. I present flexible GIS-based approaches for reformulating aggregate administrative indicators for global correlation analysis, accounting for spatial autocorrelation, and assessing perceived neighborhood geography. I assess multiple foci of the stress process paradigm using qualitative and quantitative methods, and evaluate the extent to which multiple components of social environment are implicated in psychosocial pathways, with specific attention to distinguishing socioeconomic and stress pathways.

Complex interaction between air pollution and area-level deprivation effects on term birth weight suggested differential population susceptibility, and the need for mechanism-specific non-chemical exposure metrics. Spatially, ecologic indicators of social stressor exposures and air pollution were not consistently correlated with each other, or with indicators of socioeconomic position, and were not consistently associated with child asthma exacerbation rates. Community perceptions of important social stressors assessed through a qualitative process informed upon the design and implementation of a systematic survey to validate the resonance of ecologic stressor indicators against individual stress perception and mental health. Overall, these non-chemical exposure assessment methods enable characterization of complex confounding in urban environments, toward refining epidemiologic investigations of separate and combined effects of social and chemical exposures.


Sara Gillooly, MPH

Using Deciduous Tree Leaves and Biomonitors for Particulate Matter Air Pollution: A Literature Review and Pilot Study

Particulate matter (PM) air pollution varies in concentration and composition across both space and time, and has been shown to cause or exacerbate adverse effects on human and ecological health. The concept of biomonitoring - using tree leaves as a proxy for PM pollution - has been explored using a variety of study designs, tree species, sampling strategies, and analytical methods across multiple geographies. Development and refinement of methods for utilizing tree leaves as biomonitors is relevant to public health in that it may improve spatially-resolved PM exposure assessments for epidemiological studies, ultimately contributing to PM exposure reduction and improved urban planning. A pilot study investigating this method is discussed, with results suggesting a somewhat limited utility of magnetic methods that is relatively understated in the literature.


Epidemiology

Tushar Singh, PhD

Cardiovascular Disease and Mobility Disability in Rural Older Indians: the Mobility and Independent Living in Elders Study (MILES)

Increase in older population is most rapid in developing countries and will have major impact on public health. Indian older population is not well described and there is an urgent need to estimate the burden of prevalent disease, disability and risk factors. To accomplish this, we established a longitudinal cohort study – MILES, in a rural population of older Indians. We enrolled a random sample of 562 men and women aged 60+ from rural India. Baseline visit consisted of a comprehensive clinical examination and interview. We examined the prevalence of CVD and its relationship with traditional CVD risk factors in MILES. CVD was defined as a composite of self-reported history of CVD, major ECG abnormality or peripheral artery disease (PAD). Prevalence of CVD was 24.6% in men and 25.6% in women. In multivariate analyses among men, BMI, hypertension and physical inactivity were associated with higher prevalence of CVD. Among women, chewing tobacco, hypertension and physical inactivity were associated with higher prevalence of CVD. Additionally, we estimated the prevalence and risk factors for mobility disability in MILES population by using inability to attempt or complete a 400-meter usual paced walk as a measure of mobility disability. Mobility disability prevalence was much higher in women (43.8%) compared to men (27.9%). In men, knee pain, fair vision, chronic lung disease and greater number of depressive symptoms were associated with mobility disability. Among women, waist circumference, depressive symptoms, knee pain, poor vision, CVD history and PAD were associated with mobility disability. Mean walking times were high in those men (435 seconds) and women (503 seconds) who completed the walk. Higher walking times were associated with higher waist circumference, knee pain and use of walking aid in both men and women. This dissertation has major public health significance. In this dissertation, we identified the rural older Indian population to be very frail, and with high prevalence of disease and mobility disability. There is a high prevalence of risk factors, low heath awareness and poor health care access. These data indicate urgent need for primary prevention measures and increasing availability of treatment to prevent further complications.


Health Policy and Management

Manik Razdan, PhD

The Efficiency and Effectiveness of Donor Registry Promotion and the Organ Donation Process: Impact on the Availability and the Cost of Procuring Organs for Transplant

The remarkable progress of transplant medicine in the latter half of the twentieth century has led to an unprecedented demand for donated organs that have historically remained in short supply. Although a clinically effective procedure, organ transplant’s health benefit to the society is seriously limited by the shortage of organs. The resulting tragic and preventable loss of life is therefore a public health concern. This dissertation examines the efficiency and the effectiveness of the organ procurement process and its impact on the cost and availability of transplantable organs. Specifically, three issues are examined using data from western Pennsylvania and West Virginia, a region served by the Center for Organ Recovery and Education (CORE). First, the effect of process breakdown on the availability of transplantable organs is examined using generalized linear model. The principal finding is that for every process breakdown in the care of a potential donor, one less organ is available for transplant. Consequently, 25 organs were lost to process breakdowns over the three-year study period. Second, the cost of promoting the donor registry and its effect on the supply of organ donors is examined using decision analysis model. The principal finding is that CORE’s promotion efforts would generate 4.2 present-day donors at a cost of $726,000 per donor. When compared with previously published estimates of a donor’s monetary value to the society, CORE’s promotion efforts offer good return on investment. Third, the impact of donor registry promotion on organ shortage is examined. Our analysis indicates that the impact threshold of registry promotion is reached at 64 donors that yield 73 kidneys, 45 livers, 18 lungs and 15 hearts. The principal finding is that registry promotion alone cannot arrest the growth in transplant waiting list. Although a cost-effective strategy, registry promotion has a significant budget impact. Living donation and innovations that expand the donor pool or improve the organ acceptance rate may be able to arrest the growth in the waiting list. However, burden of waiting list deaths rests primarily on the causes of end-stage organ failure rather than organ shortage. Prevention and early intervention remain the first line of defense.

Infectious Diseases and Microbiology

Julianne Louise Baron, PhD

Reducing the Public Health Impact of Infectious Caused by Waterborne Pathogens

Many opportunistic waterborne pathogens, including Legionella species, non-tuberculous mycobacteria, and Pseudomonas aeruginosa, can thrive in hot water systems despite municipal and traditional on-site disinfection. These organisms can cause healthcare-acquired infections in immunocompromised and elderly patients. This project aimed to assess and reduce the impact of waterborne pathogens (WBPs) in these populations.

In this study I developed a LAMP based assay that is specific for L. pneumophila that does not cross-react with other Legionella species or bacteria commonly found in either water or urine samples. This assay can detect L. pneumophila at a concentration of 400 cfu/mL and higher in contaminated water.

Evaluation of on-site monochloramine treatment over a two year period demonstrated a significant reduction in Legionella and total bacterial counts. The growth of other WBPs did not increase and the negative consequences seen in municipal monochloramine addition were not observed. Using Illumina sequencing I showed that the resulting shift in water microbial ecology over the course of monochloramine treatment was immediate and not gradual over time. This sequencing analysis revealed an increase in the relative abundance of certain non-Legionella WBPs throughout the course of chloramination. While molecularly the relative abundance increased, the total culturable bacterial counts decreased, likely resulting in no change overall.

I conducted a different sequencing study to look at the comparison of monochloramine treated and control water sampled at the same time points. This analysis showed significant differences in the richness, evenness, and composition of microbes present, related to treatment.

A field evaluation of a new point-of-use faucet filters showed them to be effective in preventing exposure to Legionella for 17 weeks. While these filters did not exclude all heterotrophs, there was a significant reduction in the amount of total bacteria and the three species present in filtered samples have not been found to cause human disease.

These studies have public health significance because they aid in the rapid detection of L. pneumophila, the cause of most cases of Legionnaires’ disease. They have also evaluated the effects of on-site monochloramine disinfection and point-of-use filtration to prevent exposure to Legionella and other opportunistic waterborne pathogens.

2016 Awardee Abstracts

Behavioral and Community Health Sciences

Flor de Abril Gonzalez Alburquerque, MPH

An evaluation of the parents as teachers model at the Latino family center in Pittsburgh, PA

BACKGROUND: The Latino Family Center of Pittsburgh has been implementing the Parents as Teachers (PAT) model since 2009, targeting all Latino Families with 0-5 year olds in Allegheny County, Pennsylvania (PA). PAT strategies include home visiting, group connections, developmental screening, and service coordination. 

OBJECTIVE: The purpose of this project was to develop and implement an evaluation plan for the PAT program at the Latino Family Center. 

METHODS: Participant observation, meetings with stakeholders (i.e., parents, staff, and program director) and a literature review served as the methods to develop the evaluation plan. A tailored logic model was developed based on the PAT national logic model. A diagram depicting local program implementation was also developed. The evaluation implementation used a mixed methods approach to answer the evaluation questions identified by the program administration and involved a standardized family survey, a quality measures assessment, and documentation review. 

PUBLIC HEALTH SIGNIFICANCE: Through the PAT program, Latino families have improved access to social and health services that would otherwise be quite difficult to obtain. This evaluation will provide the PAT program with valuable information for program improvement. 

RESULTS: Overall, the results indicate a positive change in parenting practices among the sample (n=40). Across all 12 items, parents reported an average improvement of 1.2-points on the parenting practices ladder. Those surveyed also reported being very satisfied with the services at the Center. Opinions on the helpfulness of the PAT activities indicated that when parents participate, in general they find them very helpful. However, a large percentage of the parents who participated in survey reported not participating in certain program components. 

CONCLUSIONS: Results suggest that the PAT model as implemented at the Latino Family Center is having a positive impact on those who participate in the program. Areas of improvement include increasing parent participation in all program components, encouraging fathers to participate, increasing efforts to get parents to read to their children and continued evaluation efforts.

 

Biostatistics

Xuan Li, MS

Statistical Analysis of Infectious Disease Data on Networks

Purpose: Infectious disease modeling has a long history in helping researchers to understand the complex spread pattern of infectious disease. Social contact networks and agent-based models can be used to conceptualize social contact pattern and spread process of infectious disease. The goal of this research is to investigate the relationship between network measurements and individual infection risk using statistical analysis. 

Public Health significance: This research will help in gaining a better understanding of the important factors of infection risk in a population. Identification of central people may be used to inform building an efficient surveillance and prevention program. 

Methods: Three social contact network models were used in this thesis, Erdos-Renyi network, Barabasi-Albert network and Jefferson County contact network using FRED platform. We simulated mild and severe epidemic outbreaks on them and calculated infection risk and infection speed of each individual. Network measurements, degree, betweenness centrality, closeness centrality, eigenvector centrality, PageRank, and clustering coefficient were measured on the ability to identify groups of different infection risk level and infection speed. Random Forest and variable importance were used to estimate the most important factors in predicting infection risk

Results: For Barabasi-Albert and Erdos-Renyi networks, centrality measurements are critical factors in identifying infection risk. Degree is the most important factor in Barabasi-Albert network while closeness and degree are the most important in the mild outbreak and severe outbreak respectively in the Erdos-Renyi network. Results of Jefferson County contact network in FRED find out the importance of location sizes. The highly clustered structure of location-based model makes betweenness centrality and clustering coefficient important in predicting infection risk.

Conclusion: Different network structures and characteristics of the disease will influence the importance of network measurements. Network structures also influence the correlations between network measurements. Random forest is a powerful tool for classifying infection risk. Centrality network measurements may help in identifying high infection risk people.


Zhen Zeng, PhD

A pipeline for classifying close family relationships with dense SNP data and Putative Pedigree Information

When genome-wide association studies (GWAS) or sequencing studies are performed on family-based datasets, the genotype data can be used to check the structure of putative pedigrees. Even in datasets of putatively unrelated people, close relationships can often be detected using dense single-nucleotide polymorphism/variant (SNP/SNV) data.

A number of methods for finding relationships using dense genetic data exist, but they all have certain limitations, including that they typically use average genetic sharing, which is only a subset of the available information. We present a set of approaches for classifying relationships in GWAS datasets or whole genome sequencing datasets. We first propose an empirical method for detecting identity-by-descent segments in close relative pairs using unphased dense SNP data and demonstrate how that information can assist in building a relationship classifier. We then develop a strategy to take advantage of putative pedigree information to enhance classification accuracy. Our methods are tested and illustrated with two SNP array datasets from two distinct populations. With these new techniques, we propose classification pipelines for checking and identifying pair-wise relationships in datasets containing a large number of small pedigrees.

We also explore the performance of the pipeline on a whole exome sequencing dataset. Although the classifier based on SNP array data does not perform well on exome sequencing data, it can in principle be modified using new algorithm parameters and training data in order to achieve better performance.

Finally, we develop a method to reconstruct pedigrees from pair-wise relationship information. Our method can reconstruct core pedigrees with high accuracy and pair-wise relationship inferences can be further improved during this process.

Detecting close family relationships and reconstructing pedigrees are important in both population-based and family-based studies. Providing precise pedigrees and hidden relatedness information helps increase the accuracy and power of various genetic analyses and avoids false positive associations, making these studies more efficient in identifying the genetic basis of diseases. This is a crucial step on the path to developing better treatments and interventions and improving public health.


Environmental and Occupational Health

hirunwut Praekunatham, MPH

Spastic Paraparesis: Putative Toxicants, Determinants and Contributing Factors in Public Health

Cassava is a staple food in many tropical countries, most notably Africa. Consumption of cassava, especially the bitter cassava varieties, can lead to a neurological disorder called “spastic paraparesis” or “konzo” in West Africa; most often epidemic outbreaks rather than isolated cases. Children and women of childbearing age are the most susceptible groups. Because of the irreversible neurological deficit caused by this disease, children and women with konzo suffer from lifelong disabilities starting at an early age. This essay aims to examine the public health determinants, including contributing factors, and identify the putative toxicant(s) that leads to spastic paraparesis. A non-systematic literature review was performed using papers retrieved from the MEDLINE database. Spastic paraparesis is strongly related to chronic consumption of cassava combined with a sulfur-containing amino acid deficiency. The majority of published studies suggest that cyanate is the most likely toxicant leading to motor deficit. Food crisis, provoked by economic stagnation, drought, war, and famine, is associated with insufficient food processing to remove cyanogens from cassava. Several public health interventions can be implemented to prevent the occurrence of konzo in communities that rely on cassava as a staple food, including conducting health education programs, promoting cultivation of low-toxin strains of cassava, and effectively conserving environments. The surveillance system for konzo should be strengthened in high-risk areas. Furthermore, a community-based rehabilitation program aimed at the disabled people should be established in the affected villages.


Epidemiology

Mustapha Munir Mustapha, PhD

Global Emergence and Persistence of Hypervirulent capsular Group W Sequence type (ST)-11 Neisseria Meningitidis

Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally. Beginning with an epidemic among Hajj pilgrims in 2000, capsular group W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African ‘meningitis belt’ and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate less virulent W ST-11 strains in circulation since 1970 from the Hajj epidemic strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters were caused by direct descendants of the Hajj clone. This work analyzes whole genome sequences of a global collection of over 250 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2014 using phylogenetic analyses, detailed examination of the capsule gene cluster (cps) and genes encoding major surface antigens. 

We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. We identified two distinct, conserved, recombination events within W ST-11 cps genes with W ST-22 and Y ST-23 as most likely donor lineages. In addition, the Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone further recombination involving virulence genes encoding factor H binding protein (fHbp), nitric oxide reductase (nor), and nitrite reductase (aniA). These data suggest that the W ST-11 capsular switch involved two separate recombination events and that current global W ST-11 meningococcal disease is caused by strains bearing this capsular switch. Emergence of the Hajj clone may be related to recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes. 

This study resolves questions about the Hajj epidemic strain that were unanswered for 15 years. Furthermore, the findings of this study help illuminate genomic factors associated with emergence and evolution virulent meningococcal strains.

Public Health significance: This dissertation provides genomic markers that reliably distinguish epidemic from sporadic W ST-11 strains that are applicable to molecular surveillance of N. meningitidis. Data presented in this work also demonstrate the need for a group W vaccine disease in the meningitis belt that can be potentially used beyond the meningitis belt in South Africa, parts of Latin America, and Europe that are facing the emergence of W ST-11.


Nayana Nagaraj, MPH

The Role of Mediator Complex Subunit 12 (MED12) in the Murine Reproductive Tract

The risk of cardiovascular disease (CVD) increases in women after menopause along with levels of complement protein C3. Recent data has shown higher cardiovascular fat in postmenopausal women. Increasing evidence suggest this fat depots are a source of cytokines and various inflammatory markers. Both complement protein C3 and cardiovascular fat are associated with increased risk of CVD. The association between these factors needs to be evaluated in women at midlife.

Hypothesis: Circulating complement protein levels in women at midlife are positively associated with arterial calcification, and this association can be explained by higher volumes of cardiovascular fat.

Methods: Pilot data from the SWAN were used. C3 and C4 were measured by immunoturbidimetric assay. EBCT scans were used to measure the arterial calcification (aortic-AC and coronary-CAC) using Agatston scores and the volumes of fat around the heart (total heart adipose tissue-TAT) and the descending thoracic aorta (perivascular adipose tissue-PVAT). Arterial calcification and fat volumes were log transformed. Tobit regression was used for statistical analyses.

Results: A total of 100 women (50% late peri/postmenopausal; 73% Caucasian) were included. In models adjusted for age, race, menopausal status, and LDL-C, C3 was significantly associated with both CAC (β(SE)=0.43(0.17),p=0.012) and AC (0.59(0.28),p=0.036) per 1 standard deviation increase of C3 (SD=33.28 mg/dl). Additional adjustment for either TAT or PVAT nullified the association of C3 with both CAC and AC. Association between C3 and AC was more pronounced at higher volumes of TAT, independent of potential covariates (p=0.036). C4 was not associated with any of the calcification measures.

Conclusions: Higher levels of C3 were significantly associated with greater CAC and AC scores in women at midlife. These associations were explained by volumes of TAT and PVAT. Our findings extend support to the outside-in theory of atherosclerosis and suggest TAT as a potential source of circulating C3. Similar results are reported in unhealthy populations. The public health significance lies in the fact that by extending these findings to the general population, we have potentially found a non-invasive biomarker that could be useful in early diagnosis of subclinical atherosclerosis. These findings need to be replicated in larger samples.


Health Policy and Management

Ashley Oates, mha

Developing a collaborative, Patient-Centric Approach for Adolescent Transition from Pediatric to Adult Health care

Pediatric hospitals are primed to be the main driver of creating successful transition programs for adolescents with special health care needs.  With more than 11 million children in the United States affected by special health care needs, a seamless process for preparing, assessing and completing a transition from pediatric care to adult care is paramount. This essay aims to identify a transition structure that addresses the needs of many types of patients who are transitioning from pediatric to adult hospitals, but specifically focuses on the high population of adolescents with special health care needs.  The Children’s Hospital of Pittsburgh of UPMC (CHP) will serve as a data model and case study for supporting the author’s recommended transition structure, as CHP serves more than 9,500 adolescents each year. Core components of transition should be addressed in a pediatric hospital-led transition program will focus on the patient.  A patient-centric transition program should transcend condition, socioeconomic status, number of specialists involved, and most importantly, physical hospital walls. The author recommends a set of immediate and future goals for CHP based on literature findings and current processes. These recommendations address the areas of patient-centric and transition-focused programming, team composition, clear programmatic direction, and the appropriate use of technology. In terms of public health, this topic addresses a potential barrier in the continuum of care and desired health outcomes for the foundation of our society: children and their families. 

Human Genetics

Priya Mittal, PhD

The role of Mediator Complex Subunit 12 (MED12) in the Murine Reproductive Tract

Uterine leiomyomas are benign neoplasms arising from smooth muscle cells of the uterus. They are clinically diagnosed in 25% of women and are associated with significant morbidity. Whole exome approaches have identified heterozygous somatic mutations in the mediator complex subunit 12 (MED12) in about 70% of leiomyomas with a majority harboring in exon 2 of MED12 with c.131G>A being the most common SNV. MED12 protein is part of the large mediator complex and is involved in transcriptional regulation of RNA Polymerase II. To elucidate the role of MED12 exon 2 variants in leiomyomagenesis, we generated three different mouse models of Med12; loss-of-function, dominant-negative and gain-of-function mouse models. 

The loss-of-function females lacked any leiomyoma-like lesions, instead the reproductive tracts were hypoplastic and the females were infertile. 

We engineered a model where we conditionally floxed Med12 c.131G>A cDNA and inserted into the ROSA26 locus to generate Med12 ROSA knock-in mice. Amhr2-cre was used to drive the expression of the mutant Med12 from the ROSA locus either in the absence (gain-of-function) or presence (dominant-negative) of X-chromosome wild-type Med12 in the uterine mesenchyme. Uteri from (gain-of-function) females displayed leiomyoma-like lesions in about 87% of females. Similar characterization of uteri of dominant negative females revealed the development of leiomyoma-like lesions, but with appearance of smaller lesions and lower penetrance (50% of females) as compared to the gain-of-function model, leading us to conclude that the Med12 exon 2 variants are likely to cause uterine leiomyomas via gain-of-function mechanism. 

Array comparative genomic hybridization (aCGH) of mouse tumors displayed genome wide aberrations, affecting general tumor pathways. Interestingly, several regions previously implicated in human leiomyomas were also shared by the mouse leiomyomas, revealing the similarities between human and mouse leiomyomas. This data suggests that Med12 exon 2 mutations are precursors to genomic rearrangements leading to an unstable genome. The public health significance of this work includes the successful development of the first animal model for uterine leiomyomas, which will be an invaluable tool to understand the role of MED12 in leiomyoma genesis, as well as provide a unique platform to test targeted therapeutics as an alternative to hysterectomies.


bess Wayburn, mS

Psycosocial impact of targeted exome sequencing of chronically ill children

Whole exome sequencing (WES) is a relatively new testing option, currently offered primarily in the pediatric setting, that is open to more uncertainty than single gene or gene panel testing. This uncertainty makes pre-test counseling challenging yet critical to ensure informed consent. Adaptation of counseling strategies for this type of testing requires a better understanding of parents' experiences throughout the WES testing process. However, the experience of parents of chronically ill children who have actually gone through the entire WES testing process has not been widely reported in the literature. Currently, analysis of exome test results at Children’s Hospital of Pittsburgh does not include the incidental findings that are typically reported in WES results (i.e. variants in genes that are not associated with the child’s present condition) and is, therefore, referred to as “targeted exome sequencing” (TES). This study was designed to gain an understanding of the psychosocial impact on parents of the TES testing process for chronically ill children in order to improve test education, consent and results disclosure processes, and to better help parents cope with the results. Semi-structured interviews were conducted with 11 parents of children who received targeted exome sequencing results and thematic analysis was performed on transcripts generated from the interviews. The experiences and opinions of parents whose children received positive, likely negative or uncertain results were analyzed, in order to develop a robust understanding of the full TES process. This study has Public Health significance because the results may contribute to the development of updated recommendations for optimizing informed consent and results disclosure for TES.

Infectious Diseases and Microbiology

Marilyn Blasingame, MPH

Mongolia: Opportunities for Control of Sexually Transmitted Infections

Sexually transmitted infections are a public health concern affecting a large portion of the population of Mongolia, and STIs put an unnecessary strain on the Mongolian health system. Many of these infections are preventable, and with the concerted effort of public health officials and local public health workers, the burden of sexually transmitted infections in Mongolia has the potential to be lifted by application of the Social-Ecological framework in consideration with the cultural, environmental, and population factors of public health significance that have a major effect on health and health decision making.  These factors must be addressed when developing effective, sustainable prevention and treatment response through a focus on treatment and practice, policy, and education for sexually transmitted infections in Mongolia.

Pediatric hospitals are primed to be the main driver of creating successful transition programs for adolescents with special health care needs.  With more than 11 million children in the United States affected by special health care needs, a seamless process for preparing, assessing and completing a transition from pediatric care to adult care is paramount. This essay aims to identify a transition structure that addresses the needs of many types of patients who are transitioning from pediatric to adult hospitals, but specifically focuses on the high population of adolescents with special health care needs.  The Children’s Hospital of Pittsburgh of UPMC (CHP) will serve as a data model and case study for supporting the author’s recommended transition structure, as CHP serves more than 9,500 adolescents each year. Core components of transition should be addressed in a pediatric hospital-led transition program will focus on the patient.  A patient-centric transition program should transcend condition, socioeconomic status, number of specialists involved, and most importantly, physical hospital walls. The author recommends a set of immediate and future goals for CHP based on literature findings and current processes. These recommendations address the areas of patient-centric and transition-focused programming, team composition, clear programmatic direction, and the appropriate use of technology. In terms of public health, this topic addresses a potential barrier in the continuum of care and desired health outcomes for the foundation of our society: children and their families. 


Yanille Scott, PhD

The Potential of Broadly Neutralizing HIV Antibodies to Function as Microbicides

Microbicides are products designed for vaginal or rectal use to prevent transmission of the human immunodeficiency virus (HIV). The first generation non-antiretroviral (nonARV) microbicide candidates were intended to be a low-cost, female-controlled method of HIV prophylaxis because young women in the poorest regions of the world are disproportionately affected by HIV. However, these early microbicide candidates were not HIV specific and some disrupted the vaginal epithelium, increased immune activation in the female genital tract, or disturbed vaginal flora, while others simply did not work. Due to the poor clinical success of these first-generation candidates, there was a shift in focus to developing antiretroviral (ARV) compounds like tenofovir and dapivirine as microbicides. However, ARV-based microbicides may not prevent transmission of drug-resistant HIV. Moreover, not all persons may want to use an ARVbased product due to the potential of drug side-effects and the risk of developing drugresistance if the product is used inappropriately. While there has been progress in developing a product for oral HIV pre-exposure prophylaxis (PrEP), there are still no commercially available topical microbicide products. Topical microbicides are desirable because they deliver active agents directly to the vaginal or rectal mucosa where HIV transmission occurs while avoiding systemic drug exposure. Hence non-ARV based microbicides are of great public health significance as a user-controlled tool for reducing the sexual transmission of HIV toward achieving the 2030 Sustainable Development Goal of ending AIDS and ensuring good health and well-being for all. Consequently, several years after the failure of the first generation of non-ARV vaginal gel microbicides, the lessons learned from these early trials have given rise to more rigorous preclinical evaluation protocols and novel formulation and delivery technologies for microbicides. This has resulted in renewed interest and new approaches to developing non-ARV microbicides. The new generation of non-ARV microbicide candidates being developed includes active biologics like broadly neutralizing monoclonal antibodies. This dissertation presents a pre-clinical evaluation of the potential of unformulated monoclonal HIV neutralizing antibodies to function as topical HIV microbicides in vitro and using human ex vivo models of rectal and vaginal mucosal transmission. 


David Hay, MPH

Periodontal Disease Among Community-Dwelling Diabetics: Evidence From a Diabetes Education and Promotion Event

Periodontal disease is a chronic inflammatory condition and a major cause of tooth loss. The public health impact of periodontal disease is great. Nearly half of adults in the United States are affected by some degree of periodontal disease. The prevalence of periodontal disease increases with age and is closely related to certain systemic diseases such as diabetes. Diabetes is a chronic metabolic disease associated with a hyper-inflammatory state. Well-controlled diabetes will help to improve the periodontal condition, decreasing the public health impact of the disease.

Objective. The objective of this investigation was to study the prevalence of periodontal disease in a population of community-dwelling adults attending an all-day diabetes awareness and education event.

Methods. Retrospective study of periodontal disease and its relationship with diabetes. Data were collected from attendees at the Diabetes Expo in Pittsburgh, Pennsylvania, an event sponsored by the American Diabetes Association. Informed consent was obtained. Comprehensive periodontal examinations were performed. Information on age, gender, education, smoking, diabetes, periodontal disease, and oral health were collected and analyzed.

Results. Participants = 206 individuals; 97 respondents had periodontal disease and 147 did not. Ninety-three (93) individuals (47.9%) without periodontal disease had diabetes and fifty-four (54) individuals (36.3%) did not have diabetes; this finding was not significant (p=0.847). Good oral health was important among the people attending this event. Those with good oral health had less diabetes compared to people with poor oral health; this finding was statistically significant (p=0.004).

Conclusion. Retrospective investigation of periodontal disease among community-dwelling diabetics in this study revealed no significant relationship between diabetes and periodontal disease (p=0.847), although oral health was an important, significant factor (p=0.004). Further prospective research with larger sample size is recommended to confirm these findings.

© 2017 by University of Pittsburgh Graduate School of Public Health

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