Doctor of Philosophy

dissertationIn the dissertation, I use verisimilitude to explain first, how the force of visual rhetoric operates in works of art; second, for understanding how visual rhetoric influences audiences framed as both rhetorical and aesthetic viewing practices; and finally, how art is mediated in cognitive and emotional ways. Works of art call our attention to the power of these types of intercommunication because ""as often as language teaches us to see,"" Michael Ann Holly wrote, ""art instructs us in telling."" Specifically, this framework highlights that audiences of visual rhetoric rely on two types of viewing practices: first, a rhetorical practice that focuses on argument, function, and symbol; and second an aesthetic practice that focuses on the sensory, emotional, and artistic features of an image. These practices help us understand how audiences historically may have experienced works of art that evoked an emotional response and a symbolic meaning. This framework is simultaneously novel and traditional. It is novel because contemporary visual rhetoric scholarship has focused mainly on the functional and symbolic aspects of visual images and my dissertation (re)introduces aesthetic aspects of visual images in seeking to create a more holistic perspective on visual rhetoric. It is traditional because we can locate an aesthetic or visual theory in Aristotle's Rhetoric, for example in the enigmatic metaphor, bringing-before-the-eyes. In two case studies in two chapters--Comparing Pity and Fear in Rhetoric and Poetics; and The Rhetoric of Vanitas Painting--I demonstrate that the effect of this metaphor is not explicitly cognitive; but instead, a perceptive and emotional capacity. Aristotle's theory allows the audience to participate in the persuasive process and encompasses its role as the target of emotional appeals. This dissertation offers an alternative approach to the study of visual rhetoric and reminds us that we should revive an ancient perspective on rhetoric. Ultimately, I argue that rhetoric circumscribes aesthetics, which is a challenge to the conventional assumption that rhetoric and aesthetics are different phenomena

Directed Trans-Differentiation of Thymus Cells into Parathyroid-Like Cells Without Genetic Manipulation

Replacement of a diseased organ with an autologously derived tissue is an ideal therapy for some medical problems. However, it is difficult to recreate many adult human tissues in vitro due to the functionally necessary architecture of most organs and the lack of understanding of methods to direct the development of the organ of interest. The parathyroid gland is ideal for in vitro organ development because this gland is relatively simple, is transplantable, and is commonly affected by a surgical complication rather than an autoimmune disease. We have investigated thymus as a source of autologous endoderm and parathyroid-like precursor cells. Human thymus cells were treated with a differentiation protocol we developed with human embryonic stem cells (The Bingham Protocol) that utilizes timed exposures to Activin A and soluble Sonic hedgehog (Shh). We incrementally changed the protocol to optimize the differentiation of the thymus cells into parathyroid-like cells. The final protocol used 50-ng/mL Activin A and 100-ng/mL Shh over 13 weeks. The differentiated cells expressed the parathyroid markers parathyroid hormone (PTH), calcium sensing receptor, chemokine receptor type-4 (CXCR4), and chorian-specific transcription factor (GCM2) as measured by reverse transcription-polymerase chain reaction and PTH enzyme-linked immunosorbent assay. Cultured thymus cells without Activin A or Shh exposure did not secrete PTH nor express similar markers. The differentiated cells released PTH, which was suppressed in response to increased calcium concentration. The chemically differentiated cells did not form tumors in immune-compromised mice. Our protocol recreated cells with markers of parathyroid tissue that responded as parathyroid cells to physiologic stimuli. This approach is a further step toward a strategy to restore parathyroid function using autologous cells that were directed to differentiate by nongenetic in vitro manipulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90464/1/ten-2Etec-2E2011-2E0170.pd

A Portrait of North Carolina School District Superintendents, 2000-2021

This study profiles superintendents in North Carolina public-school districts for academic year 2020-2021. We focus on superintendent gender, race, educational experiences, highest degrees earned, and professional longevity; and personal characteristics such as age and marital and parenting status, and the relationship between gender and race and geographic region served. Data sources included a survey of all of North Carolina’s public-school district human resources directors; licensure and payroll records from the North Carolina Department of Public Instruction (NCDPI) for the years 2000, 2010, and 2021; and The American Superintendent: 2020 Decennial Study from the American Association of School Administrators. Despite progress, we found significant disparities between superintendent demographics and their communities. Amid growing diversity, only 26% of public- school districts were led by females and 22% percent by an African American or Latinx. We also noted high turnover, inexperience, and interim appointments as red flags. We recommend actionable steps for research, policy, and practice

Differentiation of Human Embryonic Stem Cells to a Parathyroid-Like Phenotype

Iatrogenic hypoparathyroidism is the most common complication of cervical endocrine surgery. Current management is limited and palliative. As the molecular steps in parathyroid development have been defined, they may be replicable in vitro, with a goal of cellular replacement therapy. Human embryonic stem cell (hESC) lines were investigated as a model for parathyroid regeneration in vitro. BG01 was selected as a model based on expression of genes of interest in embryoid bodies (EBs). Established strategies for mouse embryonic stem cell differentiation into definitive endoderm were modified and extended to maximize the expression of definitive markers of parathyroid development. The optimal approach included the use of Activin A at 100 ng/mL with BG01 cells grown on murine embryonic fibroblasts for 5 days under conditions of increasing serum concentration. After 5 days, the cells were allowed to mature further in tissue culture without murine fibroblasts but with continuous Activin A. Our strategy produced differentiated cell cultures that expressed intermediate markers of endoderm and parathyroid development (CXCR4, EYA1, Six1, and Pax1), as well as markers of committed parathyroid precursors or developed parathyroid glands (glial cell missing-2 [Gcm2], CCL21, calcium sensing receptor [CaSR], and parathyroid hormone [PTH]). We further characterized the cells by testing conditioned medium from various time points in our differentiation scheme for the presence of PTH. We found that by keeping the cells in culture 2 weeks after the withdrawal of Activin A, the cells were able to produce PTH. Further in vivo work will be needed to demonstrate proper functionality of the cells developed in this way.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78132/1/scd.2008.0337.pd

A comparison of in situ bottom pressure array measurements with GRACE estimates in the Kuroshio Extension

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 35 (2008): L17601, doi:10.1029/2008GL034778.Ocean bottom pressure estimates from Gravity Recovery and Climate Experiment (GRACE) have been validated by comparisons with an array of in situ bottom pressure measurements. The 600 km by 600 km array comprised 46 bottom pressure sensors that were part of the Kuroshio Extension System Study (KESS). Validations in other ocean regions have been limited by available data to pointwise bottom pressure measurements. Spatially-averaged monthly-mean bottom pressure over the KESS array is highly correlated with GRACE bottom pressure estimated at the center of the array. The correlations are nearly equally high for three standard choices of spatial smoothing radius applied to GRACE estimates, 300, 500, and 750 km. In contrast, pointwise comparisons between GRACE and individual bottom pressures are high or low in sub-regions of KESS, depending partially upon the local variance of deep mesoscale eddies whose energetic length scales are shorter than 300 km. KESS is a suitable validation experiment for the GRACE estimates at monthly scales with 300 to 750 km spatial radius of smoothing.This work was supported by NSF grant OCE-0221008

Systemic lupus erythematosus phenotypes formed from machine learning with a specific focus on cognitive impairment

OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B. CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments

Barriers and facilitators to person-centred infection prevention and control: results of a survey about the Dementia Isolation Toolkit

Objectives: People working in long-term care homes (LTCH) face difficult decisions balancing the risk of spread of infection with the hardship that infection control and prevention (ICP) measures put on residents. The Dementia Isolation Toolkit (DIT) was developed to address the gap in ethical guidance on how to safely and effectively isolate people living with dementia while supporting their personhood. In this study, we report the results of a survey of LTCH staff on barriers and facilitators regarding isolating residents, and on the use and impact of the DIT. Design: Online survey. Setting and Participants: Participants (n=208) were staff working on-site in LTCH in Ontario, Canada since March 1, 2020, with direct or indirect experience with the isolation of LTCH resi-dents. Methods: LTCH staff were recruited through provincial LTCH organizations, social media, and the DIT website. Survey results were summarized, and three groups compared, those: 1) unfamiliar with, 2) familiar with, and 3) users of the DIT. Results: 61% of respondents identified distress of LTCH staff about the harmful effects of isola-tion on residents as a major barrier to effective isolation. Facilitators for isolation included delivery of 1:1 activity in the resident’s room (81%) and designating essential caregivers to provide support (67%). Almost all respondents (84%) reported an increase in moral distress. DIT users were less likely to report an impact of moral distress on job satisfaction (OR 0.41, 95% CI 0.19-0.87) with 48% of users reporting it was helpful in reducing their level of distress. Conclusions and Implications: Isolation as an ICP measure in LTCH environments creates mor-al distress in staff which is a barrier to its effectiveness. ICP guidance to LTCH would be strength-ened with the inclusion of a dementia-specific ethical framework that addresses how to minimize the harms of isolation on both residents and staff

Prevalence, causes, and consequences of moral distress in healthcare providers caring for people living with dementia in long-term care during a pandemic

Healthcare providers caring for people living with dementia may experience moral distress when faced with ethically challenging situations, such as the inability to provide care that is consistent with their values. The COVID-19 pandemic produced conditions in long-term care homes (LTCHs) that could potentially contribute to moral distress. We conducted an online survey to examine changes in moral distress during the pandemic, its contributing factors and correlates, and its impact on the well-being of LTCH staff. Survey participants (n=227) working in LTCHs across Ontario, Canada were recruited through provincial LTCH organizations. Using a Bayesian approach, we examined the association between moral distress and staff demographics and roles, and characteristics of the LTCH. We performed a qualitative analysis of the survey's free-text responses. More than 80% of LTCH healthcare providers working with people with dementia reported an increase in moral distress since the start of the pandemic. There was no difference in the severity of distress by age, sex, role, or years of experience. The most common factors associated with moral distress were lack of activities and family visits, insufficient staffing and high turnover, and having to follow policies and procedures that were perceived to harm residents with dementia. At least two-thirds of respondents reported feelings of physical exhaustion, sadness/anxiety, frustration, powerlessness, and guilt due to the moral distress experienced during the pandemic. Respondents working in not-for-profit or municipal homes reported less sadness/anxiety and feelings of not wanting to go to work than those in for-profit homes. Front-line staff were more likely to report not wanting to work than those in management or administrative positions. Overall, we found that increases in moral distress during the pandemic negatively affected the well-being of healthcare providers in LTCHs, with preliminary evidence suggesting that individual and systemic factors may intensify the negative effect

Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance

This white paper provides updated International Transporter Consortium (ITC) recommendations on transporters that are important in drug development following the 3rd ITC workshop. New additions include prospective evaluation of organic cation transporter 1 (OCT1) and retrospective evaluation of organic anion transporting polypeptide (OATP)2B1 because of their important roles in drug absorption, disposition, and effects. For the first time, the ITC underscores the importance of transporters involved in drug-induced vitamin deficiency (THTR2) and those involved in the disposition of biomarkers of organ function (OAT2 and bile acid transporters)

Improving Benefit-harm Assessment of Therapies from the Patient Perspective: OMERACT Premeeting Toward Consensus on Core Sets for Randomized Controlled Trials

Objective: Outcome Measures in Rheumatology (OMERACT) convened a premeeting in 2018 to bring together patients, regulators, researchers, clinicians, and consumers to build upon previous OMERACT drug safety work, with patients fully engaged throughout all phases. Methods: Day 1 included a brief introduction to the history of OMERACT and methodology, and an overview of current efforts within and outside OMERACT to identify patient-reported medication safety concerns. On Day 2, two working groups presented results; after each, breakout groups were assembled to discuss findings. Results: Five themes pertaining to drug safety measurement emerged. Conclusion: Current approaches have failed to include data from the patient’s perspective. A better understanding of how individuals with rheumatic diseases view potential benefits and harms of therapies is essential