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.