Traumatic Brain Injury (TBI) is a significant public health concern that affects an estimated 5.3 million Americans. Approximately, 1 out of every 60 individuals experience a disability related to TBI, thus highlighting the significant burden on the affected population (ASBMB, 2021). A study conducted by Sharma et. al, stated that only 40.8% of individuals were able to return to employment after two years of experiencing BI, while a significant proportion of 20% remained unable to resume work due to the secondary deficits of their BI (2022). Evidence indicates that return-to-work (RTW) rates among individuals diagnosed with BI are significantly lower due to physical and cognitive deficits. The presence of unemployment, especially among the BI population can result reduced opportunities for community engagement, a loss of sense of purpose or identity, and a notable decline in overall quality of life (QoL). Occupational therapy (OT) is critical in the development of employability skills necessary for successful community reintegration including RTW. Despite this connection, there is no training module for professionals to refer to when delivering prevocational services to individuals with BI. In the attempt to bridge this gap, the Comprehensive Intervention for Prevocational Programming (CIPP) was developed and implemented. The CIPP represents an OT centered approach designed to facilitate the RTW process following a brain injury (BI). The primary goal of CIPP is to provide professionals with education on the prevocational process, enabling successful RTW. This intervention is structured around four modules, each serving distinct purposes: introduction to prevocational services, examination of BI's impact on RTW, outlining covered services, and defining the Occupational Therapy Practitioner's (OTP) role within the prevocational sector. Results of the study provided clinical evidence supporting the effectiveness of the CIPP as an impactful tool in educating professionals on the delivery of pre-employment services and further defining the role of the OTP in this domain. / Temple University. College of Public Health / Health and Rehabilitation Sciences

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During a concussion, mechanical forces cause neuron cell strain that initiates dysfunction through the indiscriminate movement of ions through protein channels. Extracellular glutamate binds with cell membrane proteins (e.g. NR2A), which exacerbates the Ca2+ ion influx and prolongs neuron dysfunction. Genetic variation may be a factor in regulating glutamate binding and therefore cell recovery time. The NR2A subunit of NMDA contains a variable (GT)n nucleotide tandem repeat (VNTR) within GRIN2A promoter region. This VNTR has been shown to regulate transcription levels in a length dependent manner, where longer repeat decreases transcription of the NR2A subunit. The purpose of this study was to determine the association of the GRIN2A VNTR and recovery (days) as well as concussion severity scores within concussed athletes. The independent variable was VNTR (long allele vs. short allele). The primary dependent variable, recovery time, was defined as injury date to return to play (RTP) clearance date as determined by the physician. Participant RTP time was categorized as normal ( 20 days). Secondary dependent variables were assessed at the initial evaluation and included vestibular ocular score, Balance Error Scoring System (BESS) score, and Immediate Post Concussion and Cognitive Testing (ImPACT) module scores. All 51 participants were athletes, comprised of 38 males and 13 females with a mean age of 18.69  6.65. Participants were evaluated at a university concussion center. The standardized concussion evaluation consisted of cranial nerve, vestibular ocular tests, balance (Balance Error Scoring System), signs and symptoms (s/s), and neurocognitive (ImPACT) testing. Each participant was genotyped via saliva sample for the GRIN2A (GT)n repeat polymorphism (rs3219790). Data analysis consisted of descriptive and inferential statistics. Chi-squares were used to assess the association between VNTR (long allele versus short allele) and concussion recovery (prolonged versus normal). Regression analyses were used to estimate extent to which non-genetic factors and genotype contributed to concussion recovery group assignment. One-way ANOVAs were used to identify any significant differences in vestibular ocular, BESS, and ImPACT module scores between long and short alleles. Primary potential non-genetic contributing factors were age, race, sex, concussion history, dizziness at time of injury, history of migraines, and history of ADHD. The alpha level was set at p ≤ .05. There were no differences between demographic or health history within the VNTR or recovery groups. There was a significant association (x2 = 4.01, p = 0.045) between the VNTR group (dominant model: LL versus SS + LS) and recovery, where the chance of prolonged recovery was 4.3 times greater for carriers of the homozygous long allele. There were no differences in concussion severity scores between VNTR group and concussion severity scores. This was the first study to investigate the association of the (GT)n VNTR within GRIN2A. We established a DNA collection, estimation, and genotyping protocol of the (GT)n VNTR for 96 samples and demonstrated accuracy of this genotyping method. Clinically, athletes carrying the long allele genotype may be predisposed to prolonged recovery following a concussive injury. / Kinesiology

Although cycling offers many health and environmental benefits, it is not an activity free of injury risk. Increases in cycling popularity in the United States over the past 15 years have been paralleled by a 120% growth in cycling-related hospital admissions, with injuries to the head among the most common and debilitating injuries. Bicycle helmets can reduce head injury risk and are presently required to meet safety standard certification criteria specifying a minimal level of acceptable impact protection. However, the conditions surrounding cyclist head impacts are thought to be much more complex than the test conditions prescribed in standards and have important implications related to mechanisms of injury. The overarching aim of this dissertation was thus to investigate the protective capabilities of bicycle helmets in the context of real-world impact conditions and relevant head injury mechanisms. This aim was achieved through a series of studies, the objectives of which were to: compare helmet impact performance across standards impact testing and more realistic, oblique impact testing; to probe how changing boundary conditions of oblique impact testing may influence helmet test outcomes; to use this knowledge to inform the development of an objective helmet evaluation protocol reflective of realistic impact conditions and related head injury risks; and finally, to enhance the body of knowledge pertaining to cyclist head impact conditions via advanced helmet damage reconstruction techniques. The compilation of results across these studies serves to enhance cyclist safety by stimulating improved helmet evaluation and design while simultaneously providing objective, biomechanical data to consumers, enabling them to make safety-based purchasing decisions. / Doctor of Philosophy / Although cycling offers many health and environmental benefits and is increasing in popularity in the United States, it is not always a perfectly safe activity. The number of cycling-related hospital admissions in the US has been increasing over the past 15 years. Cyclists often sustain head injuries from crashes, which can be particularly debilitating. Fortunately, wearing a helmet can protect against head injuries during a crash. Bicycle helmets are presently designed around safety standards that drop a helmeted dummy head onto a horizontal anvil and require the helmet to limit the force on the head to acceptable levels. However, standards tests overly simplify how cyclists actually hit their head during a crash and are consequently unable to assess how well helmets protect against common brain injuries like concussion. The overarching goal of this research was to evaluate how effectively bicycle helmets protect cyclists from concussion in realistic impact scenarios. Several studies were conducted to achieve this goal. Their individual objectives were to: compare how bicycle helmets reduce impact forces associated with standards tests versus more realistic, angled impact tests; to understand how changing constraints of an angled impact setup influences helmet effectiveness; to develop an unbiased evaluation protocol for bicycle helmets based on realistic cyclist crash scenarios and concussion risk assessment; and finally, to further explore how cyclists impact their head in real-world crashes using advanced techniques for reconstructing bicycle helmet damage from actual accidents. All of these studies lead to improved cyclist safety by stimulating improved helmet evaluation and design, while also providing consumers with information on how protective their helmets are.

The research presented in this thesis aims to improve the knowledge of head impact biomechanics in youth football players by analyzing head impact exposure of youth football players and the performance of youth football helmets. The results of the studies presented provide a foundation for researchers, football leagues, and helmet manufactures to implement changes and modifications that aim to reduce concussion risk in youth athletes. The first study presented in this thesis aims to quantify the head impact exposure of 7 to 8 year old football players and determine the cause of variation in player exposure. To conduct this study, 19 players were instrumented with helmet mounted accelerometers that measured real-time acceleration data on the field. This data was analyzed to determine the magnitude, frequency, and location of each impact sustained by players in the 2011 and 2012 football season. From these data, it was determined that the average 7 to 8 year old player experienced 161 impacts per season, 60% of which were in practice and 40% were in games. The median impact for 7 to 8 year old players was 16 g and 686 rad/s². The magnitude of the 95th percentile impact was 38 g and 2052 rad/s². A total of 125 impacts above 40 g were recorded, 67% of which occurred in practices and 33% occurred in games. It was determined that returning players experienced significantly more impacts per season than first time players and practices had significantly higher magnitude impacts than games. These data can be used to further develop practice modifications that aim to reduce total impacts and high magnitude impacts experienced by youth football players. The second study presented in this thesis aims to quantify differences in youth football helmet performance before and after a football season. Currently, the only requirement regarding helmet recertification and reconditioning states that no helmet older than 10 years will be recertified or reconditioned. Quantitative data is needed to either support or refute this guideline and provide data describing how often youth football helmets should be recertified and reconditioned. To conduct this study, 6 youth Riddell Revolution football helmets, 3 that were new and 3 that had been used for one season, were tested on a drop tower from various heights and impact locations before and after the 2013 football season. It was determined that there was no significant difference in helmet performance before and after a season for new helmets or helmets that had been used for one season. In addition, there was no significant correlation between the frequency of impacts, the 95th percentile impact magnitude, or the product of the frequency and 95th percentile impact magnitude with the change in helmet performance. Future studies should be conducted that analyze the performance of youth football helmets over the course of multiple seasons. / Master of Science

Keratins are fibrous structural proteins found in human hair that have been used to develop bioactive and biocompatible constructs for a wide variety of tissue engineering and healthcare applications. Their ubiquity, capacity for self-assembly, ease of use and versatility in blended materials, and ability to modulate cell behavior and promote tissue ingrowth have made keratins well-suited for the development of regenerative therapies. In particular, keratins have demonstrated bioactivity in both in-vivo and in-vitro studies, by altering immune and stem cell phenotype and function and promoting an anti-inflammatory/wound healing environment. This work seeks to build on previous research by investigating the ability of low and high molecular weight keratins to augment anti-inflammatory primary macrophage phenotypes and examining the influence of keratin biomaterials on cellular and inflammatory mechanisms in two models of injury and disease. Rodent models of blast induced neurotrauma (BINT) and severe osteoporosis were used to inform the development of 2D and 3D in-vitro models of macrophage/endothelial cell injury and osteogenic differentiation respectively. Keratin biomaterials exhibited some potential to alter macrophage and endothelial cell dynamics following blast, specifically by promoting anti-inflammatory (M2c-like) macrophage polarization and diminishing endothelial cell injury responses (i.e. endothelial glycocalyx shedding). A more clinically relevant model of osteoporosis found that stem cells harvested from older, osteoporotic animals demonstrated limited proliferative and bone differentiation potential compared to healthy cells. However, 3D constructs (especially keratin-based materials) were able to enhance calcification and osteogenic gene expression of diseased cells. These results highlight the complexity of macrophage phenotypic switching and cellular dynamics in these systems. However, keratin-based therapeutics may prove useful for facilitating tissue regeneration and limiting detrimental inflammatory and cellular responses in various models of injury and disease. / Ph. D.

There are currently over 40 million unpaid care partners in the United States, and this number is anticipated to rise in the coming years. Most often, the care partner is a family member of the care receiver who has no prior experience in the caregiving role. Due to the unexpected nature of an acquired brain injury, whether traumatic or nontraumatic, family members are often allocated to this role without any warning while simultaneously trying to process the trauma that has just occurred. Many of these new care partners do not feel adequately prepared to navigate the varying physical, cognitive, and emotional needs of a care receiver following acquired brain injury. The term “second crisis” has been identified to describe the transition from inpatient rehabilitation to discharge home as care partners are often overwhelmed and met with feelings isolation and abandonment by the healthcare system. Care partner burden can lead to poor health outcomes and quality of life for both the care partner and care receiver. The Caring for the Care Partner program proposed here aims to mitigate the challenges faced by the care dyad when transitioning home from the hospital. Through the provision of more individualized care partner training, care partners will feel increased confidence in their role. By incorporating an occupational therapy perspective, this program acknowledges the importance of client-centered care for both the care partner and care receiver. It includes utilization of a learner profile to identify learning preferences, training for staff therapists highlighting strategies to provide more individualized care, group educational sessions for care partners on common topics faced in the caregiving role, and care partner participation in individualized training sessions with the care receiver. This doctoral project (1) discusses the theoretical and evidence base in current literature used to create the foundation of the program, (2) describes a detailed program description, (3) provides an extensive evaluation plan, and (4) addresses dissemination of information and funding to highlight future directions and sustainability of the program. Caring for the Care Partner signifies the value occupational therapists can provide in offering support to the care dyad as they transition to the home environment. Through participation in all components of the program, care partners will experience increased preparedness and confidence, which results in improved health outcomes and quality of life for both the care partner and care receiver.

Yes / Background: Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition, interpersonal, social, physical and occupational functioning; early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. Method: Studies published before November 2017 were reviewed. Six databases were searched, with additional searching of key additional documents. Studies meeting inclusion criteria were evaluated for methodological quality. Results: Six articles addressing five studies met inclusion criteria. Study designs included three randomised controlled trials (RCT), two retrospective cohorts and one case-control. Prophylactic pharmacotherapy included antidepressants, beta-blockers and statins. In one RCT, the number-needed-to-treat with sertraline to prevent one case of depression post-TBI at 24 weeks was 5.9 (95%CI: 3.1-71.1). Prescribing beta-blockers prior to TBI reduced the depression risk regardless of the specific brain trauma. TBI patients with pre-existing hyperlipidemia not treated with statins had an increased depression risk compared to those without hyperlipidemia. Conclusion: Early initiation of sertraline prophylaxis in nondepressed TBI patients shows promise to reduce the odds of post-TBI depression developing. However, in the absence of rigorous study of tolerability, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required. / The Transport Accident Commission (TAC), through the Institute for Safety, Compensation and Recovery Research (ISCRR) at Monash University, provided funding for this review.

Introduction: After a brain injury there are often long term consequences impacting on QoL. However, this is a complex issue influenced by many factors. As someone recovers and adjusts it is likely that the way in which they evaluate QoL will also change. The theory of response shift suggests people will change the way they evaluate QoL in the face of changes in their life. The aim of this thesis is to investigate what influences a QoL judgement; examining the possibility of response shift. Methods: Quantitative and qualitative methods were used in 4 studies. These were a cross-sectional design utilising an individualised QoL measure (SEIQoL-DW); a longitudinal study utilising a ‘then-test’ approach; a cross-sectional questionnaire study; and a qualitative study using Interpretative Phenomenological Analysis. Study 1 (Ch.3) Results: Correlations between the QoL measures confirm the validity of the SEIQoL-DW; however, correlations were generally stronger for the simpler Hadorn Scale. There was little overall change in mean QoL when current and retrospective judgements were compared. There was evidence for a change in what areas of life were considered most important to QoL following injury. Study 2 (Ch.4) Results: Improvements in reported QoL between baseline and follow-up were small. A then-test indicates that any effect of response shift is small, and non-significant in the current research. There was also little evidence for reprioritisation or re-conceptualisation. Examination of other factors associated with QoL suggest that brain-injury specific factors (BIGI, RBANS) play a role in predicting QoL. Study 3 (Ch.5) Results: QoL was reported as worse post-injury on both Hadorn’s scale and the QOLIBRI-OS; a difference that was more pronounced on the QOLIBRI-OS. Differences were also reported in the importance of different areas of functioning. Change in QoL as measured by the QOLIBRI-OS was significantly influenced by disability as measured by the GOSE, emotional and informational support, and upwards social comparison. Optimism as measured by the LOT, but not upwards social comparison was a significant predictor of change on Hadorn’s scale; GOSE and emotional and informational support remain significant predictors. The GOSE, emotional and informational support, emotional coping styles and optimism were significant predictors of current QoL on the QOLIBRI-OS; and emotional and informational support and optimism were significant predictors of QoL on Hadorn’s scale. Little evidence was found to suggest that the factors proposed in Sprangers and Schwartz’s (1999) model of response shift have predicted relationships with QoL. Two candidate variables were studied: optimism and social support. However neither showed the predicted pattern of relationships. Nonetheless the study supports previous work indicating an influence of optimism and social support on QoL, and indicates that these warrant further study. There were systematic difference between current and retrospective ratings of importance of domains. The level of importance given to the areas of life defined by the QOLIBRI-OS is higher after injury than before, with the exception of “personal and social life” for which there is no significant difference. The areas of life chosen to reflect that which is measured by the GOSE (“work”, “close relationships”, and “social and leisure activities”) are rated as less important with the exception of “close relationships”. These findings provide further support for the idea that QoL domains are re-evaluated after brain injury. Study 4: This was an in depth qualitative investigation of the experience of recovery and adjustment following TBI. Semi-structured interviews and Interpretative Phenomenological Analysis (IPA) were used. Interviews were conducted with 4 men who were 3, 7, 12, and 18 years post injury. Main Outcome and Results: Themes emerging from the analysis were ‘Change: In Self and World’; ‘Reaching a point of realisation’; ‘Support’; ‘Adjusting to change/Coping with day to day life’; and ‘Participation, Goals and Focus’. These themes cover how participants felt both they and their lives had changed as a consequence of their injury; ways they went about coping and adjusting to changes; the importance of support; and the significance of social integration and participation in feeling satisfied with life. Summary and Conclusions: These studies provide evidence for response shift in different ways. There is little evidence for recalibration but there is some indication that reprioritization or reconceptualization may take place. Changes in how important different areas of life are before and after injury suggest that participants are changing the way they view and make evaluations of QoL. Factors identified as being important to QoL judgements were disability, social support (emotional and informational support identified in the questionnaire study and support in the IPA), upwards social comparison, and optimism. The IPA study suggests that functional outcome and participation are important after TBI; while also identifying ways of coping and providing an insight into the experience of recovery from brain injury. The different QoL measures used provides both evidence for their validity, but also evidence for the different conceptualisations of QoL that are measured by different instruments. The findings have implications both for understanding the QoL of the individual and for research on QoL after TBI.

Background: Until recently, qualitative researchers have avoided interviewing participants with brain injuries because of the ethical and practical dilemmas which may arise and because it has been argued that they may not be able to reflect and accurately report upon their experiences. Therefore, little research has been produced which explores the personal experience of living with a brain injury. Recently, however, some researchers have challenged the view that people with brain injuries are unsuitable as interviewees in qualitative research and have, through their own research, highlighted the importance of understanding their views and perspectives in order to provide them with the best care and rehabilitation. Aims: With this in mind, and in line with current calls for more research gaining the brain injured person’s perspective, this study attempted to gain an in depth understanding of what it is like from the brain injured person’s perspective, to live with an acquired brain injury. The study focussed upon the experience of gaining consciousness following a brain injury, the experience of living with permanent memory loss, the experience of gaining awareness of deficits, the experience of losing an identity and adjusting to a new identity, the impact on relationships with friends and family and experiences as an inpatient in a Brain Injury Unit. Sources of strength and coping mechanisms were also explored. Method: Semi-structured interviews were conducted with six individuals who had severe acquired brain injuries and were inpatients in a post-acute neuro-rehabilitation unit. The verbatim transcripts of the semi-structured interviews were then analysed using Interpretative Phenomenological Analysis (IPA). Results: The analysis produced four master themes. These were: ‘Piecing together the past and becoming aware of the present’, ‘The transition from old self to new self’, ‘Sources of strength and survival’ and ‘Experiences in rehabilitation’. A description of these themes is presented with the corresponding subordinate themes. Conclusions: The clinical implications of the research and guidance for future research are discussed. The study produced a valuable insight into the personal experience of living with a severe acquired brain injury that could be used to inform rehabilitation interventions. The results also indicated that people with acquired brain injuries may experience Post Traumatic Growth.