Master of Science, The Ohio State University, 2021, Health and Rehabilitation Sciences

Manuscript 1: Methodology Dependent Variation in Volumetric Bone Mineral Density Calculation throughout the Body Introduction: Bone quality assessment using quantitative computed tomography (QCT) may provide a more in-depth and accurate assessment of osteoporosis and fracture risk than dual-energy x-ray absorptiometry (DXA). However, QCT methodologies utilizing single-scan calibration curves may not account for differential x-ray attenuation caused by the patient which may influence calculated volumetric bone mineral density (vBMD) and skew bone quality and fracture risk assessment. Methodology: Clinical CT scans were conducted on 50 male post-mortem human subjects with phantom calibration rods throughout the scan. Height and weight were collected to determine subject BMI. Hounsfield units (HU) from skeletal volumes of interest (VOIs) were collected from the lumbar spine and left femoral neck, humerus, radius, tibia, and calcaneus. The femoral neck was segmented into trabecular (Tb), cortical (Ct) and Total (Tb and Ct) VOI's, the lumbar spine and the calcaneus consisted of Tb and Total VOIs, and the humerus, radius, and tibia were assessed for Ct bone. HU from each VOI was converted to vBMD using both a general scan specific (Gen.) calibration curve constructed from phantom rods within the CT slices of the lumbar region and location specific (LS) calibration curves constructed from phantom rods in slices for each of the skeletal VOIs. Results: Significant variation in vBMD calculated from Gen. and LS calibration curves was observed in the femoral neck, calcaneus, and tibia in all skeletal compartments 15 (p<0.01). However, no significant differences were observed in any of the lumbar spine, humerus, or radius VOIs (p>0.01). Additionally, BMI was not able to explain variation in vBMD values at any site (p>0.01). Conclusions: Using a single calibration curve to calculate vBMD in other anatomical locations, may skew bone quality and differential fracture risk ass (open full item for complete abstract)

Committee: Randee Hunter PhD (Advisor); Amanda Agnew PhD (Committee Member); Jun Zhang PhD (Committee Member) Subjects: Anatomy and Physiology; Biomedical Research; Health; Health Care

Doctor of Psychology (Psy.D.), Xavier University, 2020, Psychology

Trait mindfulness is stable over time and has been shown to predict health-related quality of life (HRQOL), mood disturbances, and other symptoms of distress in certain cancer populations. In the current study of 43 bone and blood cancer patients receiving a bone marrow transplant (BMT), the researcher investigated whether levels of trait mindfulness served as a protective factor from the psychological and physical burden of the procedure. Additionally, the association between two commonly used mindfulness measures was examined. The researcher utilized two baseline measures of trait mindfulness along with three measures of treatment-related outcomes—HRQOL, mood disturbances, and post-traumatic stress disorder (PTSD) symptoms—both before and after BMT. Correlational analyses assessed the degree of association between the two mindfulness measures. Six hierarchical regression analyses tested the predictive power of trait mindfulness on the three outcomes. Contrary to the hypotheses, results indicated that levels of trait mindfulness failed to significantly predict ratings of HRQOL, mood disturbances, and PTSD symptoms following BMT. This BMT-sample was unique in its comparatively high levels of trait mindfulness. Two measures of trait mindfulness, the FFMQ-15 and MAAS, were moderately, positively correlated, but only the FFMQ-15 Nonreacting subscale was significantly correlated with the MAAS. Our results apply to oncological settings, suggesting BMT patients may benefit from interventions that teach how to utilize mindfulness for healthier coping. Future research should consider measuring the effects of cancer treatment on mindfulness levels, as well as the associations between mindfulness and treatment-related outcomes up to a year post-BMT.

Committee: Jennifer Gibson Ph.D. (Committee Chair); Lyn Sontag Psy.D., ABPP (Committee Member); Nicholas Salsman Ph.D., ABPP (Committee Member) Subjects: Psychology; Psychotherapy

Doctor of Nursing Practice Degree Program in Population Health Leadership DNP, Xavier University, 2018, Nursing

The effects of sleep loss are a population health issue for the 65.7 million family caregivers in the United States (U.S.). Between 60-95% of caregivers report poor sleep quality because of sleep disruption. The purpose of this Doctorate of Nursing Practice (DNP) scholarly project was to evaluate the effectiveness of a combination of interventions, referred to as a sleep bundle, to improve sleep quality for caregivers of children with chronic conditions such as bone marrow transplant (BMT) using the FADE (Focus Analyze Develop Execute Evaluate) quality improvement (QI) methodology. It was hypothesized that the sleep bundle will decrease sleep disruption, and ultimately improve the sleep quality of primary caregivers of BMT patients. Specific aims to test the hypothesis included: (1) Compare sleep efficiency and quality in caregivers with and without the sleep bundle; (2) Identify and mitigate barriers and obstacles to implement the sleep bundle. Although the sleep bundle was followed reliably the nights of sleep bundle intervention phase; the sleep bundle was not found to be statistically significant in improving the sleep efficiency and sleep quality of caregivers of BMT patients. Additional evaluation of the sleep bundle and its impact on improving the sleep efficiency and quality of caregivers is needed with a larger sample size. Possible alteration of specifics interventions combined in the sleep bundle should also be explored.

Committee: Elizabeth Bragg PhD, RN (Committee Chair); Robin Saxon DNP, RN (Committee Co-Chair) Subjects: Health Care; Health Sciences; Medicine; Nursing; Psychology

Doctor of Philosophy, The Ohio State University, 2018, Anatomy

Current measures of skeletal health rely heavily on the quantification of bone mass, oversimplifying the complex and multifaceted nature of bone tissue. Though diminished bone quantities do correlate with increased fracture incidence, bone mass is increasingly proving to be only one of a multitude of factors influencing the lifelong integrity of the skeleton. Bone quality, a multifaceted approach to bone health, considers all the components of bone, from nanostructure to macrostructure, and their interactions to develop a holistic approach to bone health. At the microstructural level, linear microcracks, a form of cortical microdamage, act as a toughening mechanism of the bone and are thought to be a major contributor to fracture risk. Known to contribute to the formation of fatigue fractures, where accumulated damage within the cortex results in whole bone failure, current understanding of in vivo levels of microdamage is limited. Additionally, work has focused predominantly on cyclic loading and fatigue, without considering the role cortical level damage may play in failure from a traumatic load. This study lays out detailed methods for the preparation and analysis of linear microcracks in cortex of the human rib. Revised criteria for counting and measuring cracks is detailed in order to reduce the subjectivity of such measurements, with the aim of improving intra- and inter-observer error. These methods are then applied to a sample of 30 individuals, 15 females and 15 males, ranging in age from 40–99 years of age. Paired 6th ribs were required from each individual, one to act as a baseline of in vivo microdamage prevalence and the other to be used in experimental testing. Using the control ribs, in vivo microdamage was assessed for the influences of age and sex. Neither of these demographic variables proved to have any influence on microcracks in the study sample. The test ribs were placed in an experimental fixture where they were impacted to failu (open full item for complete abstract)

Committee: Amanda Agnew (Advisor); John Bolte (Committee Member); Yun Seok Kang (Committee Member); Mark Hubbe (Committee Member); Samuel Stout (Committee Member) Subjects: Anatomy and Physiology; Biomechanics; Physical Anthropology

Doctor of Philosophy, Case Western Reserve University, 2017, EMC - Mechanical Engineering

A significant effort continues to be directed towards improvements in the current assessment methods of bone quality, while in parallel, research into understanding of the fracture resistance is accelerating for assessing collagen matrix and water portions of bone since current diagnostic methods do not encompass the crucial contribution of these variables to bone's fracture resistance. In this perspective, identifying, describing and understanding the involvement of water and collagen matrix to the fracture resistance of bone could be central to both these efforts and would contribute to improvement of current diagnosis techniques as well as to identify new therapeutic targets. Although there are several different methods available, including microscopic, spectroscopic, physical and chemicals methods to be used for characterizing bone composition, Raman spectroscopy is the only method which can provide quantitative and qualitative information of all bone constituents (i.e., mineral, organic matrix and water), simultaneously at micron-scale spatial resolution as well as holds non-invasive potential clinical use. Therefore, over the past two decades, Raman spectroscopy has become a powerful technique to investigate alterations to bone composition associated with aging and diseases. Although a significant number of spectroscopic studies have investigated the influence of mineral quality at fabric level on bone mechanical competence, the use of Raman spectroscopy to assess collagen quality in bone is limited and the correlation between spectroscopic measurement of collagen quality and bone mechanical properties remains poorly understood. On the other hand, to date, water-related Raman bands have not been studied yet, and Raman OH stretch bands have not been related to varying water compartments within bone or other tissues. The potential of Raman spectroscopy to assess hydration status of bone as a measure of bone quality is still unknown. Therefore, there is a clear (open full item for complete abstract)

Committee: Ozan Akkus (Committee Chair); Clare M. Rimnac (Committee Member); Umut A. Gurkan (Committee Member); Steven J. Eppell (Committee Member) Subjects: Biochemistry; Biomechanics; Biomedical Engineering; Biomedical Research; Biophysics; Engineering; Mechanical Engineering

Doctor of Nursing Practice , Case Western Reserve University, 2016, School of Nursing

The importance of distress screening has been acknowledged nationally and is the recognized standard of care in oncology patients. Patients who undergo bone marrow transplant (BMT) are known to suffer from distress, which can be psychological, physical, social and/or spiritual in nature. Approximately 40-55% of BMT patients are distressed pre-transplant, a higher rate than the general oncology population. BMT healthcare providers need to be aware of the psychosocial struggles that patients experience prior to transplant and throughout their cancer trajectory. The overall aim of this scholarly project was to determine if distress screening at pre-transplantation was associated with a predicted overall QOL of BMT patients post-transplantation. Additional research questions aimed to determine the most prevalent distressing problems in this population in order to target key nursing interventions. The conceptual framework is based on the Model of QOL adapted for BMT. Key variables include distress and QOL in BMT patients. According to the National Comprehensive Cancer Network, distress is defined as “a multifactorial unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social, &/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms and its treatment”. QOL, according to Grant & Ferrell, is defined as “as a personal statement of positivity or negativity of attributes (psychological well being, physical well-being, sequel of disease and treatment, social and interpersonal well-being and financial and material well-being) that characterize one's life.” A descriptive, retrospective design was used. A convenience sample of fifty-six new allogeneic and autologous BMT patients from large Southwestern comprehensive cancer center were screened with the NCCN distress thermometer and FACT-BMT as part of routine care. Data were collected one day pre-transplant and 4-6 weeks pos (open full item for complete abstract)

Committee: Maryjo Prince-Paul Dr. (Committee Chair); Barbara Daly Dr. (Committee Member); Melanie Brewer Dr. (Committee Member) Subjects: Nursing

Doctor of Philosophy, The Ohio State University, 2015, Anthropology

The purpose of this study is to investigate variation in cortical bone osteocyte cell populations using their lacunae as a proxy. Osteocytes and their lacunocanalicular network have been identified as the regulator of bone quality and function by exerting extensive influence over metabolic processes, mechanical adaptation, and mineral homeostasis. Recent research has shown that osteocyte malfunction and apoptosis leads to a decrease in bone quality and increase in bone fragility. However, these results are limited to mainly trabecular bone in clinical studies following biopsy or prosthetic replacement in osteoporotic patients and animal studies in which experimental data have been collected. This study is the first to analyze cortical bone variation in osteocyte lacunar density from multiple skeletal sites to establish regional and systemic age and sex related trends. Bone samples were recovered from 30 modern cadaveric individuals (15 males and 15 females) ranging from 49 to 100 years old. Three anatomical sites were utilized for this study: the midshaft femur which is frequently used in anthropological studies of cross-section geometry, age estimation and behavioral interpretations as it is a major load bearing bone; the distal third of the diaphyseal radius as it represents a clinically relevant site for fractures associated with falls especially in older adults; and the midshaft of the 6th rib as this is frequently a systemic control. Histological sections were used to collect bone size measurements (total subperiosteal area Tt.Ar; cortical area Ct.Ar) using ArcGIS and ImageJ. ImageJ was then used to optimally manipulate the image in order to identify and count osteocytic lacunae (Ot.Lc.N) automatically over the entirety of the cross-section. Intracortical porosity area (Po.Ar) was collected using a semi-automatic requiring extensive manual verification and used to calculate bone area (B.Ar) for each section (Ct.Ar-Po.Ar). Each variable used for com (open full item for complete abstract)

Committee: Clark Larsen (Advisor); Samuel Stout (Committee Member); Paul Sciulli (Committee Member); Amanda Agnew (Committee Member) Subjects: Physical Anthropology

Master of Science, The Ohio State University, 2014, Comparative and Veterinary Medicine

Assessment of the proximal femoral anatomy in dogs is important for determining suitability for total hip replacement (THR) surgery, surgical planning for THR, and assessment for the risk for potential complications. Femoral anatomy has particular significance for evaluating the suitability of a patient for cementless implants that rely on a press-fit for stability in the immediate post-operative period. Breed variations in proximal femoral anatomy have been posited in the veterinary literature. In humans, variations in femoral anatomy have been identified as normal, stovepipe, and champagne-fluted; these varying morphologies have different associated bone qualities and suitability for THR. A stovepipe femur in humans is characterized by a straight, cylindrical, wide proximal femur with relatively weak trabecular bone. However, the significance of a stovepipe femoral morphology in dogs has not been determined. We hypothesize that dogs with stovepipe femora will have larger proximal femoral volumes and weaker trabecular bone than dogs with normal, conical shaped proximal femoral morphologies. Femoral morphology will be determined via three-dimensional reconstructions of computed tomography scans performed on client owned dogs presented for evaluation for THR. Trabecular bone quality will be assessed via a micro-computed tomographic scan and direct mechanical testing on cylindrical bone cores obtained at THR surgery. The results of this study will have profound implications for surgical planning for THR and will enable us to provide robust and scientifically sound recommendations for implant selection, implant design, and the assessment of potential complications following THR in dogs.

Committee: Matthew Allen (Advisor); Johnathan Dyce (Committee Member); Wm. Tod Drost (Committee Member) Subjects: Veterinary Services

Master of Science, The Ohio State University, 2014, Dentistry

Objective: The purpose of this study was to determine the effects of a guided bone regeneration (GBR) procedure on general and oral health-related quality of life. Changes in patient stress, depression, anxiety and coping levels during early wound healing were also evaluated. Material and Methods: Sixteen non-smokers (mean age 60±4 yrs; 9 males), treatment planned to receive GBR for a single large size (=2 adjacent missing teeth) defect (total of 17 sites), were recruited. Ridge width (RW) and ridge relative height (RRH), flap thickness (FT), keratinized tissue width (KTW) and clinical evaluation of the wound were recorded at surgery, 1 week, 1 month and 4 months. Wound fluid was collected and its content was studied for various wound healing related mediators. Pre- and post-surgical evaluation of perceived stress, depression, anxiety, coping and general health assessments were conducted as well as General Health (GHQ-12) and Oral Health Related Quality of Life (OHIP-49) questionnaires. Results: Size of the wounds at various anatomical locations was similar. A slight but statistically significant gain in RW was noted (7.5±0.7 mm versus 8.6±0.6 mm; p=0.02). The difference detected at RRH was not statistically significant (12±0.6 mm versus 10.7±0.8 mm; p=0.057). Mean FT was 1.3±0.1 (0.6-2.5) mm. KTW remained unchanged. Primary wound closure was obtained in all cases except one. Eighty-eight and 35 percent of the sites had clinical wound exposure at 1 week and 1 month, respectively. Actual exposure was 3.8±0.7 mm and 2±0.8 mm at 1 week and 1 month, respectively. Wound fluid volume decreased 2 fold by 1 month. Interestingly, most of the pro-inflammatory mediators reached picked levels at 1 month and not earlier. GHQ-12 and OHIP-49 scores were stable throughout the study. Eighty-eight and 44 % of the patients reported some pain at surgical site at 1 week and 1 month. Baseline mean Depression Scale (CES-D) score was 7±2 with only two patients having =16. A statistically n (open full item for complete abstract)

Committee: Binnaz Leblebicioglu (Advisor); Dimitris Tatakis (Committee Member); Lisa Christian (Committee Member) Subjects: Dentistry

Master of Science, The Ohio State University, 2012, Veterinary Clinical Sciences

Proximal femoral bone quality and quantity are two important variables to provide long-term stability in cementless total hip arthroplasty (THA). The goal of this study is to determine the feasibility of using non-invasive imaging data to predict the quality and quantity of cancellous bone in the canine proximal femur and directly compare this with bone microstructure and mechanical analysis. Twelve cadaveric canine femora were used. Radiographs were taken, along with DEXA scans and quantitative CT. Bone Mineral Content (BMC) and Bone Mineral Density (BMD) were measured from DEXA scans and CT, and radiographs were scored. Cores of cancellous bone were harvested from the proximal femur. High-resolution micro computed tomography (uCT) was performed to assess bone microstructure (fractional bone volume BV/TV, polar moment of inertia). Direct mechanical testing of the bone core was performed to assess bone strength (break load, stiffness, energy at break). Pearson correlation was used to compare the biomechanical parameters with the imaging modalities. uCT values (BV/TV and AMI) had the best predictor of mechanical properties of cancellous bone in the proximal femur, while clinical imaging modalities such as radiographs, DEXA BMD and BMC and qCT had only mild correlation with predicting bone strength. uCT has the best predictor of bone strength, suggesting that bone architecture plays a significant role in determining bone strength. CT, DEXA and radiographs all showed only mild correlation of bone strength, indicating that clinical parameters are not useful in predicting proximal femoral bone strength.

Committee: Matthew Allen (Advisor); Richard Hart (Committee Member); Valerie Samii (Committee Member); Jonathan Dyce (Committee Member) Subjects: Veterinary Services

Doctor of Philosophy, The Ohio State University, 2011, Anthropology

The purpose of this study is to characterize the variable microstructure of the elderly human rib in an attempt to elucidate its contributions to biomechanical adaptive responses and fragility. Histological sections were made from Basic Fuchsin stained bilateral 6th ribs from 10 elderly post-mortem human subjects (PMHS). Percent Porosity Area (% Po.Ar), mean Osteon Area (On.Ar), mean Crack Length (Cr.Le), Crack Density (Cr.Dn), and Crack Surface Density (Cr.S.Dn) were successfully quantified and analyzed. ANOVA results indicate that all variables show significant inter-individual variation, but no significant bilateral variation within individuals. Subject variation could contribute to differential individual fragility. Paired t-tests revealed cortex differences for these variables (most are significant) between compressive and tensile cortices in a presumed cyclic bending loading pattern in the rib. These findings can contribute to interpretations about loading history and mechanical adaptation as well as bone behavior prior to failure. A methodological investigation into microfracture data collection showed significant differences between a “total” dataset and a “sampled” dataset. Therefore, it is recommended that only microfracture data collected from the entire rib cortex be utilized in future studies until a more representative sampling method can be developed. This study should prompt investigators to incorporate a histological perspective into interpretations as to why and how bone failure may occur and what contributes to fracture risk in the elderly rib in both modern and past populations.

Committee: Samuel Stout PhD (Advisor); Clark Spencer Larsen PhD (Committee Member); Paul Sciulli PhD (Committee Member); Kenneth Jones PhD (Committee Member) Subjects: Aging; Anatomy and Physiology; Biomechanics; Evolution and Development; Health; Histology; Physical Anthropology