MS, University of Cincinnati, 2019, Medicine: Clinical and Translational Research

Background: The optimal approach for management of spontaneous pneumothoraces (SPs) and the safety of air travel in patients with pulmonary Langerhans cell histiocytosis (PLCH) are not well established. Methods: Patients with PLCH were recruited from the Rare Lung Diseases Clinic Network and the Histiocytosis Association, and surveyed about disease manifestations and safety of air travel. Results: A total of 94 patients completed the survey. Median age at diagnosis of PLCH was 40 years (range: 15-67 years). Average interval between symptom onset and diagnosis was 2.9 years (range: -4 to 31 years). Twenty-two patients (23%) had at least one SP, of which 14 (64%) had at least one additional SP that showed either an ipsilateral recurrence (10 patients; 45%) or a contralateral recurrence (8 patients; 36%). Mean age at the time of first SP was 29 years. SP was the presenting manifestation that led to the diagnosis of PLCH in 19% of patients, typically after the second episode. Surgical pleurodesis reduced the recurrence rate of SP by half in comparison with conservative management (29% vs. 65%, p = 0.025). Two patients experienced an episode of SP during air travel, consistent with an air travel-related pneumothorax rate of 2.4% per patient and 0.27% per flight. Conclusions: SP is a common manifestation of PLCH, can be seen in approximately one-fourth of the patients, and has a high recurrence risk. Surgical pleurodesis leads to a substantial reduction in the SP recurrence risk. The risk of an air travel-related SP in patients with PLCH is about 2-3 per thousand flights.

Committee: Patrick Ryan Ph.D. (Committee Chair); Nishant Gupta M.D. (Committee Member) Subjects: Surgery

PhD, University of Cincinnati, 2018, Medicine: Pathobiology and Molecular Medicine

Dendritic cells (DCs) are the most efficient antigen presentation cells and execute a pivotal role in the onset and regulation of innate and adaptive immune responses and the recruitment of a variety of leukocytes to the site of inflammation or injury. To counter the challenge of the non-stop exposure to exogenous pathogens, the lungs developed an intrigue and complex immunology defense orchestra that conducted by DCs. An increasing volume of research on DCs in recent years show that the disruption of DC equilibrium in the lung may result in different diseases. In this study, we used two different disease models to elucidate the importance of DC in disease pathogenesis. Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by focal DC accumulation, bronchiolocentric nodule formation, and cystic remodeling of the lung and occurs predominantly in active smokers. Approximately 50% of PLCH patients harbor somatic BRAF-V600E mutations identified mainly within the DC lineage. However, the rare nature of the disease and lack of animal models impedes the study of the pathogenic mechanisms of PLCH. We have established the first mouse model that recapitulates the hallmark characteristics of PLCH. In addition, we show that the BRAF-V600E mutation is associated with increased DC responsiveness towards multiple stimuli including the DC-chemokine CCL20. We provide evidence that DC accumulation in the lung is due to both increased viability and enhanced recruitment. Further evidence indicates that the accumulation of other inflammatory cells in PLCH is a secondary event driven by CCL7 secreted from DCs in a BRAF-V600E-dependent manner. Moreover, we demonstrate that the PLCH-like phenotype in the mouse model can be attenuated following smoking cessation and removal of BRAF-V600E DCs. Furthermore, we show PBMCs isolated from PLCH patients harboring the BRAF-V600E mutation produce CCL7. Collectively, our studies provide the first mechani (open full item for complete abstract)

Committee: Michael Borchers Ph.D. (Committee Chair); Ian Paul Lewkowich Ph.D. (Committee Member); Francis McCormack M.D. (Committee Member); William Miller Ph.D. (Committee Member); Kathryn Wikenheiser-Brokamp M.D. Ph.D. (Committee Member) Subjects: Surgery

MARCH, University of Cincinnati, 2012, Design, Architecture, Art and Planning: Architecture

Libraries remain vital institutions despite changes in resources and use. Specifically, the branch library must address the challenges and opportunities of its associated community. In reaching this goal, identity and traditional functions hybridize in order to redefine the institution's vision. Research into multi-functional libraries and retail stores illuminates the library's potential to adapt through environmental branding, and envisions spaces sensitive to the unique DNA of the brand. The methodology for designing the branch library as a branded environment includes selecting brand touchpoints, structuring the site, and expanding the program to more fully engage the needs of the community. The thesis design proposal, located in Avondale, a Cincinnati neighborhood that lacks convenient resources and struggles with crime, will overhaul a 100-year-old Carnegie library facility in order to increase its prominence within the community. In the manner of Tschumi's la Villette “follies,” 16' x 10' red library cards mark the cardholder's journey across the site, focusing on five functions: technology, entertainment, nourishment, learning, and community. The proposed buildings link the site response while providing settings for technology resources and community gathering. This proposal addresses how the brand of the Public Library of Cincinnati and Hamilton County can be propelled into the community, transcending the conventional library. The research and design suggests opportunities for other PLCH branch libraries to increase brand engagement, each in accord with the specificity of its neighborhood, facility, and cardholders.

Committee: John Eliot Hancock MARCH (Committee Chair); Jeffrey Tilman PhD (Committee Member) Subjects: Architecture