Doctor of Philosophy

dissertationSurvivin is an Inhibitor of Apoptosis Protein (IAP), which is highly expressed in a number of human malignancies. It is a developmentally regulated gene that is expressed during embryogenesis, but silenced in normal adult tissue. Since its discovery in 1997, survivin function has evolved to include regulation of spindle assembly in mitosis. Melanoma arises in epidermal melanocytes, and is the most lethal dermatologic cancer due to its highly metastatic nature. In melanoma, expression of survivin has been heavily correlated to advanced disease stages and poor patient prognosis. Targeting of survivin in melanoma cells leads to induction of apoptosis in vitro and reduction of tumor growth in vivo. While the anti-apoptotic and mitotic roles of survivin have been extensively studied, the work documented in this dissertation describes a novel basis for survivin function in melanoma metastasis. Chapter 2 details a study which showed that survivin increases melanoma cell migration and invasion via Akt-dependent upregulation of α5 integrin. I also demonstrate that overexpression of survivin increases melanoma colony formation in soft agar, and this effect could be abrogated by knockdown of α5 integrin by RNA interference. These findings demonstrate that survivin can enhance cellular functions which are critical to the metastatic process in melanoma. To further investigate the functional role of survivin and α5 integrin in melanoma metastasis, I used a iv xenograft mouse model to determine the in vivo effect of survivin overexpression and subsequent upregulation of α5 integrin on melanoma metastasis (Chapter 3). The studies show that while survivin overexpression does not result in increased tumor proliferation or decreased apoptosis, it does cause increased metastasis of melanoma cells in vivo and this requires upregulation of α5 integrin. Taken together, this dissertation presents data to support an additional role for survivin function in melanoma metastasis which is α5 integrin-dependent. In summary (Chapter 4), I will discuss future research avenues looking mechanistically at how survivin upregulates α5 integrin and mediates melanoma metastasis. Additionally, I will also discuss therapeutic targeting of survivin and α5 integrin in melanoma and how the knowledge gained in this study may contribute to such efforts

Social Media Use Among Nonprofit Organizations in Rural Appalachia

Introduction: Social media have changed the landscape of health communication for nonprofit organizations (NPOs). Yet, adoption and use of social media lag among NPOs in rural Appalachia due largely to limited infrastructure development. Methods: Semi-structured phone interviews were conducted in January–March 2018 with 21 NPO representatives in an 8-county region of rural Appalachian Tennessee. NPO representatives were asked questions pertaining to social media use and message content, effective communication strategies, and best practices in social media use. Transcripts were analyzed in April–May 2018 using thematic analysis. Results: The majority of NPOs had a Facebook page and recognized its promise as a communication tool. However, due to resource constraints, most NPOs used social media as a secondary communication strategy to complement traditional approaches. In terms of messaging, NPOs used social media primarily to share information and solicit donations or volunteers. Representatives identified several obstacles to social media use among NPOs in the region. These included limited organizational resources, community infrastructure, and household resources. Implications: Social media are inexpensive communication tools that NPOs in rural Appalachia can use to expand their digital footprint into hard-to-reach populations. Therefore, eliminating the digital divide across the U.S. is an important step toward enhancing rural NPOs’ capacity to serve their communities well. Opportunities for NPO staff to access low-cost professional development and training in the use of social media, specifically for social marketing purposes, are also essential

Clinician Evaluators: Take Your Mark!

Discuss two implementation outcomes (adoption and reach) and explain why they are important for clinicians to measure and report, with application to own work. Name sources of data that are accessible to clinicians in health care settings, with consideration of own setting. Describe a range of dissemination strategies used to create impact, including new ideas for dissemination of own work. References Proctor, E. K., Silmere, H., Raghavan, R., Hovmand, P., Aarons, G. A., Bunger, A., . . . Hensley, M. (2011). Outcomes for implementation research: Conceptual distinctions, measurement challenges, and research agenda. Administration and Policy in Mental Health and Mental Health Services Research, 38(2), 65-76. doi:10.1007/s10488-010-0319-7. Polaha, J., & Sunderji, N. (2018). A vision for the future of Families, Systems, & Health: Focusing on science at the point of care delivery. Families, Systems, & Health, 36(4), 423-426. Polaha, J., Schetzina, K., Baker, M., & Morelen, D., (2018). Adoption and reach of parent management interventions in pediatric primary care. Families, Systems, & Health, 36(4), 507-512. Funderburk, J. & Polaha, J. (2017). To clinician innovators: A special invitation. Families, Systems, and Health, 35(2), 105-109 Polaha, J. & Nolan (2014). Dissemination and implementation science: research for the real world medical family therapist. In J. Hodgson, T. Mendenhall, & A. Lamson (Eds). Medical Family Therapy. Switzerland: Springer International

Clinical Evaluators Take Your Mark

Discuss two implementation outcomes (adoption and reach) and explain why they are important for clinicians to measure and report, with application to own work Name sources of data that are accessible to clinicians in health care settings, with consideration of own setting. Describe a range of dissemination strategies used to create impact, including new ideas for dissemination of own work

Ancient Latin American objects in the archive: selections from the George and Louise Patten collection of Salem Hyde cultural artifacts at the University of Tennessee at Chattanooga

https://scholar.utc.edu/exhibition-records/1004/thumbnail.jp

Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms

IntroductionThe phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.MethodsIn CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.ResultsIn all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.ConclusionEfficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.Clinical trial registrationClinicalTrials.gov, identifier NCT0281186

Health Communication Strategies Among Non-Profit Organizations in Appalachia

Social media has several advantages over more traditional forms of mass communication, but many non-profit organizations (NPOs) are underutilizing social media as a communication platform. There is limited research on social media use among NPOs in rural Appalachia. The current study fills this gap in the literature by examining social media use among NPOs in rural Appalachian Tennessee. We conducted 20 semi-structured phone interviews with NPO representatives (President, CEO, Executive Directors) in an 8-county region of Appalachian Tennessee. The interviews were transcribed and analyzed using Braun and Clarke’s thematic analysis. Thematic analysis indicated that rurality, organizational capacity, messaging, and social media as a secondary communication strategy were important themes. Fiscal, personnel, and time constraints were limiting factors in terms of NPOs ability to use social media. NPOs used social media primarily to share information with their target audience. While acknowledged as an important feature of social media, NPOs were less likely to use social media to advocate, engage, or mobilize community support. Further data collection is ongoing to confirm these findings and to identify best practices. NPOs in rural Appalachia can use these findings to enhance their communication strategies

Best Practices to Improve Social Media Use Among Non-Profits Organizations in Rural Appalachia

Introduction: The rapid growth of social media provides new opportunities for non-profit organizations to network and influence the public. Rural non-profit organizations can expand organizational capacity and reach, engage more stakeholders, and acquire new donors at a relatively low cost by using social media effectively. Despite the obvious benefits of social media, many rural non-profits underutilize this technology due to social drivers in the community and lack of organizational capacity. This is particularly salient in rural Appalachia where inequities persist in access to broadband and wireless mobile services. Eliciting insights from the experts - rural nonprofit leaders – is critical in identifying strategies to help nonprofit organizations level up social media use. There is a paucity of research on social media use among nonprofit organizations in rural Appalachia. The present study fills this important knowledge gap in the literature. Methodology: This qualitative study used purposive sampling techniques to recruit representatives from nonprofit organizations located in an 8-county region of Appalachian Tennessee. Semi-structured phone interviews were conducted in 2018 with nonprofit representatives (n=21). Nonprofit representatives were asked questions pertaining to social media use, effective communication strategies, and best practices. Probing questions were used to explore topics further. The audio recordings of the interviews were transcribed verbatim. Braun and Clarke’s thematic analysis procedures were used to conduct an in-depth descriptive analysis of participants’ responses and develop themes. Result: Four best practice strategies were identified: 1) “Know your people”—relationships matter: It is important to develop strong ties within the community; 2) “We had to come up with something fast”—resourcefulness matters: Nonprofit organizations should practice resourcefulness and adaptability in program development and outreach, 3) “Catch their attention”—the message matters: Messaging should be brief and positive in nature, and 4) “A lot of nonprofits come and go…”—the nonprofit matters: Nonprofit organizations should implement sound business practices. These themes highlight practical steps nonprofit organizations can take to enhance their social media communication strategies. Conclusion: With the emergence of sophisticated, easily accessible social media platforms like Facebook, YouTube, and Twitter, there is an urgent need to identify simple strategies rural nonprofits can employ to use social media more effectively. Our research addresses this need by summarizing the best practices in social media practices for nonprofit organizations in rural Appalachia. Nonprofit organizations in rural Appalachia can use these best practices to enhance communication strategies, expand their reach, and strengthen relationships within the communities they serve

Improving warfarin therapy through implementation of a hospital-based pharmacist managed clinic in Jamaica

Background: Pharmacist managed warfarin clinics can improve the anticoagulation status of non-valvular patients. The first of such services was implemented at the Cornwall Regional Hospital in Jamaica in 2013. Objectives: To assess the anticoagulation control of patients on warfarin therapy over six months in the pharmacist managed warfarin clinic at Cornwall Regional Hospital. Methods: Retrospective docket review for the period January 2014 to December 2016 was done to include data of patients attending routine clinic appointments for at least six months. Age, gender, date of visit, indication for warfarin therapy, warfarin dose and International Normalized Ratio readings were extracted. Percentage time spent in therapeutic range (TTR) was calculated by month for six months using the Rosendaal linear interpolation method. Patient anticoagulation status was categorized as poor (TTR<40%), moderate (TTR=40-64%) or good (TTR≥65%) and anticoagulation status at three months and six months was compared. Results: For the period of assessment, 52 patients were identified; the median age was 58 years and 36 patients were males. Deep vein thrombosis was the main indication for therapy (22 of 52) and median warfarin weekly dose ranged was 15.0-130 mg. At time of recruitment most of the patients were outside the target INR range (43 of 52). Within one month, the median TTR attained was 31% [IQR 62-10]. This significantly improved by second month to 60% [IQR 82-23] (p=0.001). By month three, the proportion of patients in good, moderate and poor anticoagulant status was 19/51, 15/51 and 17/51 respectively, which at six months changed to 23/51, 12/51. 16/51 respectively; thus, although coagulation status improved from month one to three, there was no significant improvement from month three to month six (p=0.31). Conclusions: The pharmacist managed warfarin clinic monitoring services were successful in attaining TTRs >40% and sustaining these values over six months. The services should therefore be encouraged