M.A. thesis, Faculty of Humanities, University of the Witwatersrand, 1999

Class of 2012 Abstract / Specific Aims: During pre-hospital transport, trauma patients may be given a long-acting neuromuscular blocker (NMB) to facilitate endotracheal intubation or to prevent movement. The purpose of this study was to determine the rate of long-acting NMB use and evaluate the concurrent use of sedatives. Methods: This was a retrospective cohort study conducted in a tertiary care, academic emergency department of trauma patients aged 18-89 years who were intubated in the pre-hospital setting. The primary outcome was to determine the rate of long-acting NMB use. The use of post- intubation sedatives was compared between the groups using Wilcoxon rank-sum test or Fisher’s exact test, using an a priori alpha level of 0.05 for all analyses. Main Result: A total of 51 patients were included in final analyses. All patients received etomidate or midazolam for intubation. 86% (n=44) received succinylcholine, 10% (n=5) were given rocuronium and 4% (n=2) did not receive a NMB. After intubation, 75% (n=38) received an additional long-acting NMB to prevent movement (vecuronium (n=22) or rocuronium (n=16)) . Overall, 82% (n=42) of patients received a long- acting NMB during transport. There was no difference in the rate of post-intubation sedative use between groups (79% versus 67%, respectively, p=0.42). The long-acting NMB group received midazolam less promptly after intubation (16 versus 7 minutes, respectively, p=0.04). Conclusions: The use of long-acting NMB is common during the pre-hospital transport of trauma patients. Some of these patients may not be given sedatives or have delays in receiving sedatives following intubation and be at risk of being paralyzed without sedation.

The present study included three traumatic brain injury (TBI) groups (good effort mild TBI, poor effort mild TBI, and good effort moderate/severe TBI) and two neurologic control groups (dementia and unilateral left hemisphere stroke). Language impairment was examined using the following measures: Wechsler Adult Intelligence Scale-III Verbal Comprehension Index and the Vocabulary, Similarities, Information, and Comprehension subtests; the Boston Naming Test; the Phonemic and Semantic cue conditions of the Controlled Oral Word Association Test; the Auditory Comprehension subtest of the Cognistat; Wide Range Achievement Test-3 Reading subtest; and the Peabody Picture Vocabulary Test. When effort was controlled, there was a significant effect of injury severity on language impairment. Poor effort and diagnosable malingering were responsible for most of the neuropsychological test evidence of language impairment in mild TBI.

Attention impairment is one of the most common complaints following Traumatic Brain Injury (TBI). Multiple studies have shown that performance on neuropsychological tests of attention is affected by many factors, including injury severity and effort. The aim of this study was to determine the effect of injury severity on neuropsychological tests across different domains of attention while controlling for effort. The domains of focused attention, selective attention, divided attention, sustained attention, and working memory were assessed by performance on the Digit Span Forward subtest, the Stroop Color Word Test, the Trail Making Test, the Conners' Continuous Performance Test - II, and Digit Span Backwards subtest, respectively. Effort was determined according to performance on the Portland Digit Recognition Test and the Test of Memory Malingering. Effort was found to have a greater effect on test performance (.79) than injury severity (.47). Clinical implications of the findings are discussed.

Police officers are exposed to stress outside the range of usual human experience. The operational duties of police work, by their very nature, may at any time place officers in life threatening situations (McCraty, Tomasino, Atkinson and Sundram, 1999). These life threatening situations often lead police officers to experience different kinds of trauma. Certain temperament characteristics have throughout time been implicated as vulnerabilities toward trauma (Marais, 2005). This research study aimed to investigate this relationship between temperament styles and the effects of traumatic events on police officers working as dog handlers at the SAPS Dog Unit, Soweto. An exploratory-descriptive research design with a combination of qualitative and quantitative research methods was used to address the aims of the study. Use of the Keirsey’s Temperament Sorter indicated that from the fifteen respondents who took part in this study the majority demonstrated a tendency towards extraversion, sensation, feeling and judging. The sensation subscales showed a weak, yet significant relationship with both intrusion and avoidance symptoms which were measured by the Impact of Event Scale – Revised (IES-R). In addition to the IES-R the researcher made use of a semi-structured interview schedule to determine the effects that traumatic work incidents had on the respondents. Common themes that emerged from the interviews included: denial, emotional detachment, lack of trust and a lack of selfknowledge. The main conclusion that emerged from the study was the need to empower police officers by helping them gain self-awareness in terms of their unique ways of coping with trauma.

This thesis is part of a creative arts PhD which explores the possibilities of constructed images and the memory of the South African Border War. It was presented together with an exhibition of constructed photographic images entitled BOS. In the thesis I argue that the memory of the war, an event now almost three decades past, continues to be problematic. I also argue that photographs are themselves complex and constructed objects that do not provide a simple truth about either history or memory. Photographs can supplement or support memories but they are always to be viewed with suspicion. In Chapter One I explore the limitations imposed on the speech of conscripts, both during the conflict and in the years following the conclusion of hostilities. In Chapter Two I examine the recent appearance of several ‘anti-­‐ heroic’ memoirs of the conflict written by conscripts. The use of the medical diagnosis of post-­‐traumatic stress syndrome (PTSD) in these writings is critically examined. Chapter Three focuses on a development in the ideas of the two most influential figures in the field of Anglophone photographic theory, Susan Sontag and Roland Barthes. I argue that their initial hostility to the photographic image on ethical/political grounds has been replaced by a more nuanced engagement with the power of the image. I then examine the views of two contemporary writers on photography, both deeply involved with the analysis of traumatic images: Ariella Azoulay and Susie Linfield. In Chapter Four, I engage with the artistic practice of the American photographer, David Levinthal, an important reference point for this project because of his photographic work with miniatures and toys and his place within what I describe as ‘critical postmodernism’. In Chapter Five, I examine the themes of silence and censorship as these pertain to the photography of the Border War using Susan Sontag’s notion of the “ecology of images”. I analyze the types of images which have been produced from the war, looking at the “limited photojournalism” of John Liebenberg and the role of iconic images in the propaganda war. Finally, in Chapter Six, I present an account of the process of creating the work for the BOS exhibition in which I employed a combination of strategies involving appropriation, miniaturization, and re-­‐staging.

OBJECTIVE: Osteoarthritis (OA) is a leading cause of disability worldwide. This disease is characterized by the inflammation and degradation of the cartilage and surrounding tissue in a joint. The disease manifests as either a result of years of wear and tear or after a joint injury. Post-traumatic osteoarthritis, as this latter case is named, is frequently studied since the exact trigger of the disease is known. In addition to several changes within the joint space, a significant alteration is the degradation of cartilage caused primarily by the release of inflammatory cytokines including interleukin-1 and 6 and tumor necrosis factor α. One current pharmacological treatment for the pain caused by OA is an intra-articular injection of glucocorticoids such as dexamethasone. As this is a common treatment, the goal of this research was to determine if, at the cellular level, this treatment impacts cell viability in the presence of pro-inflammatory cytokines. Another goal was to investigate how such treatment affects the progression of cartilage degradation caused by cytokines. OA results in the loss of the key extracellular matrix molecule, aggrecan, which contains negatively charged glycosaminoglycan (GAG) chains. Measurement of the amount of GAGs lost is an early indicator of cartilage degradation. In addition, biosynthesis of GAG chains can be measured to estimate the overall metabolic health of the cells. We hypothesized that dexamethasone blunts the harmful effects of proinflammatory cytokines and improves GAG biosynthesis and chondrocyte viability. METHODS: Cylindrical cartilage explants were collected from bovine knee joints and trimmed to a uniform 3 millimeters in diameter and 1 millimeter thick. Each treatment group consisted of n=6 explants from the same knee joint. In one set of experiments, these explants were subjected to two different doses of interleukin-1α (1 ng/mL and 10 ng/mL) with and without dexamethasone at 100 nM. In another set of experiments, explants were subjected to both interleukin-1α and tumor necrosis factor-α (1 ng/mL and 25 ng/mL respectively). The explants were cultured in medium for 6 days and were digested for outcome measurements on the final day. On day 4, 35S-sulfate was added to the explant medium for later measurement of radiolabel incorporation as a measure of GAG biosynthesis. Cell viability was measured on day 5 using red/green fluorescent viability dyes fluorescein diacetate (FDA) which stains live cells green and propidium iodide (PI) which stains dead cells red. RESULTS: Compared with untreated controls, explants subjected to the pro-inflammatory cytokines interleukin-1α and tumor necrosis factor-α exhibited greater glycosaminoglycan loss and a decrease in GAG biosynthesis. These treatments also decreased cell viability. Addition of dexamethasone improved cell viability compared to treatment with the cytokines. In addition, dexamethasone prevented glycosaminoglycan loss and increased GAG biosynthesis in the presence of interleukin-1α. However, dexamethasone did not prevent tumor necrosis factor-α mediated loss of GAGs. CONCLUSION: These studies demonstrated that dexamethasone inhibited specific aspects of cartilage degradation associated with inflammation in early OA. This therapeutic counteracts the degradative changes initiated by inflammatory cytokines such as interleukin-1α without compromising cell viability. Future studies are needed to identify the mechanisms of dexamethasone action and the ideal concentration to use if it is to be used as a treatment for OA following acute joint injury.

Transactive response DNA-binding protein of 43 kDa (TDP-43) is the major protein found within pathological inclusions in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) (Neumann et al., 2006). TDP-43 is a ubiquitously expressed protein mainly involved in RNA metabolism. It is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family and in its normal state is predominantly found in the nucleus. In its pathological state TDP-43 is cleaved, phosphorylated, ubiquitinated, and located in cytoplasmic or nuclear inclusions. Along with ALS and FTLD, TDP-43 is also observed in many other neurodegenerative diseases. Pathological TDP-43 inclusions have been previously reported in cases of Chronic Traumatic Encephalopathy (CTE) (King et al., 2010)(McKee et al., 2010)(Saing et al., 2012)(Hazrati et al., 2013), however no previous study has reported on the incidence and extent of TDP-43 cellular inclusions in a large cohort of autopsy cases diagnosed with CTE. This study finds that TDP-43 inclusions are a frequent feature of CTE, as TDP-43 inclusions are identified in 43% (20/47) of subjects in a CTE+, FTLD-, low-likelihood-of-AD cohort. Furthermore, this study finds that in CTE there is no consistent initial focus of TDP-43 pathology which spreads to neighboring regions as the disease progresses. Despite the lack of a clear progression of TDP-43 pathology, a TDP Staging Scheme for CTE which accurately reflects the extent and severity of TDP-43 pathology in not only the study cohort, but likely in all subjects without FTLD, was established. Four stages were identified: TDP Stage 0 showed no TDP-43 inclusions in the substantia nigra, dorsolateral frontal cortex, or dentate gyrus; TDP Stage 1 showed inclusions in either the substantia nigra or the dorsolateral frontal cortex; TDP Stage 2 showed inclusions either in the dentate gyrus or in both the substantia nigra and the dorsolateral frontal cortex; and TDP Stage 3 showed inclusions in the substantia nigra, dorsolateral frontal cortex, and dentate gyrus. Finally, a correlation was found between the presence of TDP-43 inclusions and the levels of activated microglia in the dorsolateral frontal cortex of CTE+ subjects. This finding aligns with the theory that the pathological changes of TDP-43 found in CTE are driven by the pro-inflammatory cytokines released by chronically activated microglia.

Traumatic brain injury (TBI) is a devastating disease causing disability and death, and currently there are no effective treatments available. Therefore, there is an utmost need to improve our understanding of the pathophysiology of TBI and to identify potential therapies that can provide neuroprotection after injury. The aims of this thesis were to develop an in vivo and in vitro model of TBI, in which to assess the potential neuroprotective effects of an omega-3 polyunsaturated fatty acid (PUFAs), docosahexaenoic acid (DHA). Method The controlled cortical impact (CCI) in vivo model of TBI was optimized and performed in mice. Both a behavioural (Morris water maze (MWM) for cognitive deficits) and histological endpoints (astrogliosis, lesion size and activated microglia) were used to assess severity and neuroprotective effects of DHA. An in vitro model of mechanical TBI was also set up and optimized. This model employed 3D astrocyte cultures obtained from GFP positive rat pups. The CCI impactor from the in vivo studies was used to damage the cultures, and at 24 hours, 5 days and 10 days the astrogliosis and cell number was measured. Results The optimization of the in vivo studies demonstrated that at impaction depth of 2.2 mm produced an injury that was significantly different to the sham injury, in MWM performance and increased astrogliosis. Interestingly, there was an increase in the amount of astrogliosis on the contralateral side of the brain. A second study performed using the 2.2 mm injury parameters was performed, where an injection of DHA was administered via the tail vein 30 min after injury. The DHA-treated group did not demonstrate any neuroprotection compared to the injury-only group. However, there was an increase in the amount of astrogliosis in the contralateral hippocampus of the DHA-treat group. In the fat-1 studies it was shown that older male mice performed worse in the MWM, that the fat-1 gene did not confer neuroprotection but did lead to increased astrogliosis. The in vitro study revealed that astrocytes in the lesioned gels demonstrated an increase in astrogliosis, there was also an increase in the number of cell in the cultures following the lesion. Conclusion In conclusion, the in vivo model of CCI replicated components of the human TBI including a behavioural deficit and pathophysiological changes. Omega-3 PUFAs failed to demonstrate functional neuroprotection in this model, but histologically, promoted an increase in reactive astrogliosis. The development of a novel in vitro model of focal injury in a 3D culture system, that elicits reactive astrogliosis, could be used to support further studies of the astrocytic responses to mechanical injury.

Child protection is an area of Police work that has grown in the last decade, involving Police Officers working in departments that specialise in the investigation of cases of child abuse. Although Police Officers in this field may be at greater risk of experiencing Secondary Traumatic Stress (STS), there remains a paucity of research in this area of policing. Analogies can be drawn to existing research in policing and with social service workers involved in child protection.A mixed methodology was used to conduct the study and involved a self-completion postal questionnaire, followed up by a longitudinal case study of three of the trainee Detective Officers. The questionnaire sample consisted of 63 Detective Officers involved in the investigation of child abuse within the host Police Force, including Detective Constables, Sergeants and Inspectors.The Study found that 51% of the respondents experienced a degree of STS, findings that are suggestive that STS is being experienced by a significant portion of Detective Officers who, as part of their daily duties, investigate child protection cases. The longitudinal case study found that 2 out of the 3 cases indicated that their views and experiences of the symptoms of STS changed mid way through their training.The implications for Police Forces to provide safe working environments and appropriate counselling for employees as a tool to manage stress, to inform practice and from which the basis of reasonable precautions, risk assessments, monitoring and appropriate interventions will be discussed.