Working Together more than Alone: Students\u27 Evolving Perceptions of Self and Community within a Four-Year Educational Administration Doctoral Cohort

School administrators rarely have the opportunity to confer and share their challenges with colleagues. To address this problem in 2005 the Educational Administration Department (EAD) at Central University (a Midwestern PhD granting institution located in a thriving city of about 100,00 people) created a virtual/local doctoral cohort for 14 school leaders living and working in two states. Three years into the course of study we conducted a year long inquiry that asked, How did students\u27 self-perceptions evolve within a cohort context, and how did these changes advance or retard professional learning community (PLC) growth? Our interviews had a phenomenological focus but we used symbolic interactionism to analyze them and dramaturgy to present our findings. Themes of faculty and student relationships, work and/or personal problems and dealing with technology indicated that despite some significant hurdles students\u27 identity evolutions moved the group toward becoming a PLC, a collaborative culture of thinkers

The Landscape of Obstetric Resources and Risks in Indiana: A Framework for Informing Policy

Indiana has many dedicated stakeholders and important initiatives working to ensure “more babies make it to their first birthday” and fewer mothers die of childbirth and related complications. Targeting specific efforts to the areas of greatest need can be challenging. The methods used for this landscape analysis offer a framework for contextualizing health service/system resources and public health outcomes/measures simultaneously for the purpose of targeting policy and programming. Concurrently examining OB resources and selected risk factors within Indiana counties provides important insight into the types of initiatives and interventions that may help “move the needle in the right direction.

EXPLORING THE ROLE OF DNA DAMAGE, NUCLEOTIDE EXCISION REPAIR, AND CIRCADIAN RHYTHM ON CELLULAR RESPONSE TO PLATINUM-BASED DRUGS

Platinum-based drugs are a mainstay of solid tumor treatment and act by inducing bulky DNA adducts which should ultimately result in cell death. Unfortunately, these drugs have serious side effects and rates of resistance are high; for example about half of colorectal tumors are platinum-resistant. Understanding the molecular mechanisms of resistance could help maximize efficacy by providing targets to counter drug resistance. The overall purpose of this project is to comprehensively characterize the role of DNA intrastrand adduct formation, nucleotide excision repair, circadian rhythm, and the interplay of these processes in tumor and normal tissue response to platinum-based chemotherapy. To achieve this, we used novel methods to measure repair rates, amounts, and genome-wide patterns at single-nucleotide resolution of multiple tumor models. In a panel of 10 colorectal cancer cell lines, we demonstrate that nucleotide excision repair is not an essential component of platinum resistance as all cell lines have similar nucleotide excision repair efficiencies despite the varying responses. Damage formation, however, may partially dictate oxaliplatin response as lower damage levels correlate with oxaliplatin resistance. While all oxaliplatin-resistant cell lines in this study showed low levels of platinum induced adducts, oxaliplatin sensitive cell lines showed more variation. We next sought to address factors that may lead to this variable damage formation and response in sensitive cell lines. Notably, we identify a large DNA amplification, containing many cancer related transcripts, specific to the sensitive cell lines with low initial damage. Additionally, damage repair in normal and xenograft tissues appear to oscillate throughout a 24 hour period indicating that treatment timing impacts the platinum-DNA adduct formation. The studies described in this dissertation improve our understanding of the role of DNA damage formation and nucleotide excision repair in response to platinum-based chemotherapy and provide a foundation for understanding how circadian rhythms may impact these factors.Doctor of Philosoph

Contributions of Early Care and Education Programs to Diet Quality in Children Aged 3 to 4 Years in Central North Carolina

BACKGROUND: Parents and early care and education (ECE) are the key influencers of young children\u27s diets, but there is limited information about how each contribute to children\u27s overall diet quality. OBJECTIVE: This study aimed to determine what proportion of children\u27s dietary intake occurs within the ECE setting and whether diet quality is higher at ECE centers and, consequently, on weekdays than weekends. DESIGN: This cross-sectional analysis of a larger cluster randomized controlled trial used multiple 24-hour dietary intakes measured through a combination of the Dietary Observation in Child Care protocol and parent-reported food diaries. PARTICIPANTS/SETTING: Participants (N=840) included children aged 3 to 4 years enrolled in ECE centers in central North Carolina for whom 24-hour dietary intake was captured via observation of meals and snacks consumed at ECE and parent-report of all remaining meals and snacks. Data were collected from 2015 to 2016. MAIN OUTCOME MEASURES: Diet quality at ECE and elsewhere was evaluated using the Healthy Eating Index 2015. STATISTICAL ANALYSES PERFORMED: Mixed-effects models were used to determine differences in mean Healthy Eating Index 2015 component and total scores. Models were adjusted for children\u27s age and sex and accounted for clustering within ECE centers and families. RESULTS: Children consumed approximately 40% of daily energy, nutrients, and food groups at ECE centers. The mean total Healthy Eating Index 2015 score was higher for foods and beverages consumed at ECE centers (58.3±0.6) than elsewhere (52.5±0.6) (P \u3c 0.0001). The mean total Healthy Eating Index 2015 score was also higher on weekdays (58.5±0.5) than on weekends (51.3±0.5) (P \u3c 0.0001). CONCLUSIONS: Children consume a majority of dietary intake away from ECE centers. Overall, diet quality is low, but the quality of foods consumed by children at ECE centers is higher than that consumed elsewhere. ECE centers remain an important source of nutrition and further investigation is warranted to identify ways to support both ECE centers and families to provide healthier eating environments

Partners In Training Health Professions

The demand for health professionals is outpacing supply in health care markets in Indiana and across the nation. The COVID-19 pandemic exacerbated workforce shortages, though many professions were already projected to worsen as demand for health care increases alongside population aging. Now more than ever before, the health professions training pipeline is critical to securing the health workforce and the health of our population and economy. For over 50 years, the Richard L. Roudebush Veterans Affairs Medical Center (Indianapolis VAMC) has been an active and significant figure in Indiana’s health professional training landscape. Indianapolis VAMC training initiatives have supported the clinical training needs of numerous academic affiliates and reached many thousands of students in health professions programs.VA training initiatives makes significant contributions to prepare trainees for numerous high demand health care professions

Screen Time Parenting Practices and Associations with Preschool Children’s TV Viewing and Weight-Related Outcomes

The purpose of this study was to examine associations between screen time (ST) parenting practices and 2–5-year-old children’s TV viewing and weight status. Data were collected from 252 parent–child dyads enrolled in a randomized parent-focused childhood obesity prevention trial from 2009–2012. ST parenting practices were assessed at baseline using a validated parent-reported survey. Parent-reported child TV viewing and objectively measured anthropometrics were assessed at baseline, post-intervention (35 weeks), and follow-up (59 weeks). Marginal effect models were developed to test the association between baseline ST parenting practices and children’s TV viewing, BMI z-score, and waist circumference across all time points. Limiting/monitoring ST was associated with decreased weekly TV viewing (β = −1.79, 95% CI: −2.61; −0.95), while exposure to TV was associated with more weekly TV viewing over 59 weeks (β = 1.23, 95% CI: 0.71; 1.75). Greater parent use of ST as a reward was associated with increased child BMI z-score (β = 0.15, 95% CI: 0.03; 0.27), while limiting/monitoring ST was associated with decreased BMI z-score (β = −0.16, 95% CI: −0.30; −0.01) and smaller waist circumference (β = −0.55, 95% CI: −1.04; −0.06) over the study period. These findings suggest that modifying parent ST practices may be an important strategy to reduce ST and promote healthy weight in young children

Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?

BACKGROUND: Cancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour's genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA). However, the detection of ctDNA in repeated liquid biopsies is currently limited by economic and time constraints associated with targeted sequencing. METHODS: Here we bioinformatically profile the mutational and copy number spectrum of The Cancer Genome Network's lung adenocarcinoma dataset to uncover recurrently mutated genomic loci. RESULTS: We build a panel of 400 hotspot mutations and show that the coverage extends to more than 80% of the dataset at a median depth of 8 mutations per patient. Additionally, we uncover several novel single-nucleotide variants present in more than 5% of patients, often in genes not commonly associated with lung adenocarcinoma. CONCLUSION: With further optimisation, this hotspot panel could allow molecular diagnostics laboratories to build curated primer banks for 'off-the-shelf' monitoring of ctDNA by droplet-based digital PCR or similar techniques, in a time- and cost-effective manner

A Novel Mechanism for Zika Virus Host-Cell Binding

Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic peptides representing the region containing ASN154 from strains PRVABC59 (Puerto Rico 2015) and MR_766 (Uganda 1947) were exposed to neuronal cells and fibroblasts to model ZIKV E protein/cell interactions and bound MDCK or Vero cells and primary neurons significantly. Peptides significantly inhibited Vero cell infectivity by ZIKV strains MR_766 and PRVABC59, indicating that this region represents a putative binding mechanism of ancestral African ZIKV strains and emergent Western Hemisphere strains. Pretreatment of ZIKV strains MR_766 and PRVABC59 with the PS-binding protein annexin V significantly inhibited replication of PRVABC59 but not MR_766, suggesting that Western hemisphere strains may additionally be capable of utilizing PS-mediated entry to infect host cells. These data indicate that the region surrounding E protein ASN154 is capable of binding fibroblasts and primary neuronal cells and that PS-mediated entry may be a secondary mechanism for infectivity utilized by Western Hemisphere strains