A major issue facing nuclear power stations is how to effectively deal with radioactive waste. This waste, as it comes from a reactor, is emitting large quantities of ionizing radiation which is usually confined. Another form of radioactive wastes is the mill tailings from uranium processing plants. These tailings are sites characterized by low-level chronic radiation. The mill tailings of the Vitro Chemical Plant, in Salt Lake City, Utah, have been a point of radionuclide concentration and environmental contamination for 20 years. These tailings may adversely affect both surrounding ecosystems and any biological systems seeking to become established on the site. To test the potential hazard of this site to the succession of plant species I examined the interphase chromosome volume and relative amounts of DNA per chromosome from plants growing on this site and those on a control site. These nuclear parameters indicate the relative radio-sensitivity of a species and would demonstrate the total effectiveness of the low-level chronic radiation in altering plant succession. The radiosensitive plant Tradescantia clone 02 was also grown in five soil samples from the mill tailings which represented a progressive increase in radioactivity. The purpose was to determine how effective these radiation levels are in altering reproductive integrity, fecundity, and somatic mutation rates in radiosensitive plant species. There was a difference in species composition between plant communities growing on the mill tailings as compared to the controls as determined by coefficient of community. However, there was no difference in interphase chromosome volume or relative amounts of DNA per chromosome between plants growing on these two sites. The difference in species composition is attributed to the length of time each site has been undergoing succession, with the control site in a more advanced stage. Tradescantia grown in soil with a radiation dose greater than 0.10 mR/hr had significantly reduced reproductive integrity and fecundity, as measured by the number of stunted hairs on a stamen and poll en viability, and increased numbers of somatic mutations. Based on these data the radioactive mill tailings from the Vitro Chemical Plant have the potential to alter plant successional patterns due to their detrimental effect on any species that is relatively radiosensitive.

Magister Scientiae (Occupational Therapy) - MSc(OT) / Background: One of the most significant current discussions in public health and occupational therapy is the challenges facing adults with chronic diseases. Adults living with chronic diseases experience challenges of activity limitations and occupational disruptions which may influence their health, quality of life and well-being. Chronic diseases seem to have implications for adults’ areas of occupation, client factors and performance patterns as well as performance skills. Spirituality is considered as important in the lives of adults living with chronic diseases as a coping strategy assisting them to deal with the challenges of life in relation to physical, social, emotional and functional well-being. Despite the importance of spirituality in adults with chronic diseases, there is little known about the relationship between spirituality, health-related quality of life and occupational balance among adults with chronic diseases in the Western Cape, South Africa. Aim: The aim of the study was to examine the relationship between spirituality, healthrelated quality of life and occupational balance from the perspectives of adults living with chronic diseases. Methods: A sequential exploratory mixed methods two phase design approach was used for the purpose of the study. Thus, to examine the perspectives and determine the relationship on spirituality, health related quality of life and occupational balance of adults living with chronic diseases. Furthermore, to explore and describe the perceptions of adults with chronic diseases regarding the relationship between spirituality, health related quality of life and occupational balance.

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Pseudomonas aeruginosa (P. aeruginosa) is a frequently isolated pathogen that causes septicaemia and chronic respiratory infection. It exhibits a higher mortality rate than other gram-negative bacteria and the need for effective immunotherapy is emphasised by the frequency of antibiotic resistance associated with this organism. Mucosal immunisation with a whole killed cell P. aeruginosa vaccine has previously demonstrated a significant immune response in both rodent studies and human trials. This study is a continuation of that research, with the major goal being the identification of a purified protein antigen that could form the basis of a mucosal vaccine against P. aeruginosa. Specifically, the aims of this study were the development of purification protocols for the isolation of previously untested protein antigens, assessment of the efficacy of these antigens to enhance bacterial clearance in an animal model of acute respiratory infection, determination of the immune parameters that are associated with the resolution of P. aeruginosa respiratory infection and finally, cloning of an identified antigen which demonstrated vaccine efficacy. Protocols were established to isolate proteins for use as antigens in immune response studies. The proteins purified in this study were Pa 13, Azurin, acyl carrier protein (ACP), Amidase, Aminopeptidase, KatA and Pa70. These proteins were used to immunise rats by intestinal intra-Peyer's patch (IPP) inoculation and intratracheal (IT) boost. The immunisation protocol employed was designed to target mucosal antigen-specific immune responses where the route of immunisation, Peyer's patch (PP) intestinal inoculation, is akin to the oral delivery of antigens to the gut-associated lymphoid tissue (96). Investigations of a previously uncharacterised antigen, Pa60, later identified this protein as the P. aeruginosa catalase, KatA. This study demonstrated enhanced bacterial clearance of both homologous and heterologous challenge following immunisation with KatA. The level of clearance demonstrated by KatA was promising when compared to that of killed whole cell immunisation. KatA was cloned and studies with the recombinant protein showed enhanced bacterial clearance commensurate with that of the native protein. Immunisations with other proteins identified four additional antigens which enhanced bacterial clearance; Pa13, Pa40, Pa45 and Pa70. Amino acid sequence analysis indicated that Pa13 may be a novel protein, whereas Pa40 was determined to be amidase and Pa45, aminopeptidase. Pa70 was not successfully sequenced. These proteins were effective in significantly enhancing bacterial clearance of homologous P. aeruginosa challenge. For KatA, Pa13 and Pa70, clearance was associated with a marked phagocytic cell recruitment. In contrast, amidase and aminopeptidase demonstrated clearance with a minimal cellular response. Proteins; azurin and ACP were non-protective, failing to clear a live P aeruginosa challenge. Analysis of the antigen-specific responses of these nonprotective proteins and comparison with those antigens which enhanced bacterial clearance were used to determine factors that may contribute to the resolution of an acute pulmonary infection. The study has demonstrated that mucosal immunisation using purified protein antigens can enhance the clearance of pulmonary infection with P. aeruginosa. It has also contributed to the understanding of immune responses to newfound antigens of P. aeruginosa and identified antigen-specific responses which confirm their potential as vaccine candidates.

Cognitive-behavioural based models of chronic pain contend that appraisals of harm affect the individual�s response to pain. It has been suggested that fear of pain and/or anxiety sensitivity predispose individuals to chronicity. However, other factors such as pain self-efficacy are believed to mediate between experience of pain and disability. According to this view, pain is maintained through hypervigilance towards painful sensations and subsequent avoidance. Four studies were conducted in order to evaluate the structure of fear-avoidance models of chronic pain, and also, to examine the role of hypervigilance as an underlying mechanism in maintenance of pain. In study one, using a sample of 207 consecutive patients, two models were tested. First, fear of movement model as proposed by Vlaeyen et al. (1995a) was examined. It was found that negative affectivity has direct effects on the fear and avoidance of pain, which in turn, contributes to disability. In total, fear/avoidance accounted for a significant amount of the variance of disability. In addition, severity of pain was found to increase pain disability, while itself is influenced still by negative affectivity. These findings supported the model of fear of pain as described by Vlaeyen et al. (1995a). Further, we found that self-efficacy may mediate the impact of fear of pain on disability and reduces the perceived physical disability. At the same time, self-efficacy was shown to have direct reductive impact on disability. However, both studies indicated that people who are fearful in response to pain are more likely to develop disability, although self-efficacy may play a moderating role. In the studies one, two, and three, the role of hypervigilance in over attending to pain was investigated. In study one a large sample of 168 chronic pain patients were studied. Questionnaires measuring different aspects of pain and a computerised version of the Dot-Probe Task were administered. Four types of words related to different dimensions of pain and matched neutral words were used as stimuli. Reaction times in response to the stimuli were recorded. A factorial design 3x4x2x2 and ANOVAs were employed to analyse the data. Chronic pain patients showed a cognitive bias to sensory pain words relative to affective, disability, and threat-related words. However, contrary to expectations, those high in fear of pain responded more slowly to stimuli than those less fearful of pain. These results suggest that patients with chronic pain problems selectively attend to sensory aspects of pain. However, selective attention appears to depend upon the nature of pain stimuli. For those who are highly fearful of pain they may not only selectively attend to pain-related information but also have difficulty disengaging from those stimuli. In study two, 35 chronic pain patients were compared with the same number matched healthy subjects. Both groups completed measures of fear of pain, anxiety sensitivity, depression and anxiety, in addition to dot probe task. Results indicated that both groups show similar attentional bias to sensory words in comparison with other word types. However, the level of this biasness was higher for chronic pain patients. Lack of significant differences between patients and controls is discussed in the context of possible evolutionary value of sensitivity to pain as an adaptive reaction in healthy controls, and contrary, as a maladaptive response to pain in chronic pain patients. The results of the previous research suggest that chronic pain patients demonstrate cognitive biases towards pain-related information and that such biases predict patient functioning. The forth study examined the degree to which a successful cognitive-behavioural program was able to modify the observed attentional bias towards sensory pain words. Forty-two patients with chronic pain conditions for more than three months were recruited prior to commencing a cognitive-behavioural pain management program. Participants were assessed before the program, after the program and at one-month follow-up. Results confirmed that chronic pain patients exhibited biased attention towards sensory pain-related words at pre-treatment. These biases were still evident at post-treatment, but were no longer statistically significant at follow up. Multiple regression analyses indicated that the changes in attentional bias towards sensory words between post-treatment and follow-up were predicted by pre- to post- treatment changes in fear of movement (Tampa Scale for Kinesiophobia) but not other relevant variables, such as fear of pain or anxiety sensitivity. These results demonstrate that successful cognitive-behavioural treatments can reduce selective attention, thought to be indicative of hypervigilance towards pain. Moreover, these biases appear to be changed by reducing the fear associated with movement. Theoretically, these results provide support for the fear of (re)injury model of pain. Clinically, this study supports the contention that fear of (re)injury and movement is an appropriate target of pain management and that reducing these fears causes patients to attend less to pain-related stimuli.

Systemic lupus erythematosus (SLE) is a relatively rare autoimmune disease with no known aetiology or cure. In addition to numerous physical symptoms, those living with SLE have also been shown to experience significant emotional and psychosocial difficulties. There has been little psychological research into SLE despite the rapidly increasing interest in health psychology and quality of life issues over the last two decades. One such issue that has commanded particular attention is that of cognitive bias in individuals with chronic pain and/or chronic illness. Cognitive bias toward illness-related information is theorised to indicate the presence of an illness self-schema, and is a valuable tool of investigation as it permits access to a level of cognitive structure that is inaccessible via self-report instruments. The primary focus of the present study is to investigate recall bias for pain- and illness-related words in SLE patients. This bias is explored relative to the recall of neutral words and depression-related words, and also relative to the responses of rheumatoid arthritis (RA) patients and healthy controls. Two hypotheses are proposed: firstly, that bias is related to disease activity; and secondly, that bias is related to the combination of illness and depression. The findings provide support for the second hypothesis, with the additional caveat that the nature of the pain/illness stimuli used is important in determining the presence of cognitive bias. No recall bias for illness-related words as a whole was found in any of the groups, nor was there evidence of a recall bias in the SLE and RA patients when they were divided according to depression status. However, when the illness words were examined separately according to �sensory pain� and �disability-related� words, a clear bias for disability words was found in the depressed patient group. It is concluded that there is a relationship between depression in chronically ill individuals, and the way in which such individuals process disability-related words. In accordance with the schema-enmeshment model (Pincus & Morley, 2001), it is suggested that both a pain-schema and an illness-schema exist, and it is when these two schemas become enmeshed with the self-schema that depression occurs in chronic pain/chronically ill patients. The cognitive bias assessment paradigm adopted in this study-one that is typically used in similar investigations-is lengthy, requires sophisticated equipment and can be difficult to interpret on an individual level. The present study investigates the relationship between cognitive biases in SLE patients and a recently-developed task, PRISM, which appears to symbolise the enmeshment of illness-, pain- and self-schemas. Analyses confirmed that recall of negative illness words was the only independent predictor of PRISM scores. This suggests that PRISM, a quick and easy task to administer, may have considerable usefulness as a clinical tool to assess information relevant to the enmeshment of illness- and self-schema. A greater understanding of schema and the processing styles of chronically ill patients will allow for more effective psychological treatment such that quality of life can be improved.

Chronic Fatigue Syndrome (CFS) is a contested condition that generates scepticism and occupies a marginalised position within medical and social contexts. The thesis examines the illness experiences, and specifically the experiences of self, for people affected with CFS. Using qualitative inquiry, a substantive theory related to the process of self-renewal and adaptation associated with CFS is explicated. The theory encompasses the trajectory of CFS from onset to chronicity, and in exceptional instances, recovery. Illness narratives were derived from in-depth, semi-structured interviews of 19 adults, including 16 people affected with, and 3 people recovered from, CFS. Data was coded and analysed using a grounded theory approach. Analysis generated two parallel narratives that defined the illness experience of CFS: the narrative of the illness biographies and the narrative of self, specifically the struggling and diminished self seeking renewal. The illness biographies encompassed the stories of symptoms and their explanations, the encounters that ensued and their contentious milieu. The narrative of self was the primary narrative. It articulated the negative consequences to self and personhood associated with CFS, named the Violation of Self, and the consequent efforts of participants to decrease the struggle and violation by use of the Guardian Response and the Reconstructing Response. The Guardian Response provided protection and self-reclamation. The Reconstructing Response fostered self-renewal and meaning. The two narratives were bridged by the threats of CFS. That is, the illness biographies were accompanied by threats of disruption related to chronic illness, and by threats of invalidation that arose from CFS as a contested condition. In turn, these threats provided the catalyst to the violation and responses as described in the narrative of self. Under different conditions the relative strengths of violation, guardianship or reconstruction fluctuated, and it was these fluctuations that presented the participants with the ongoing struggle of CFS.

Understanding the factors that regulate the growth and differentiation of haemopoietic stem cells (HSC) remains a major challenge. In this study, the proliferation and differentiation of CD34+ cells from normal donors and chronic myeloid leukaemia (CML) patients was compared. The proliferation and entry of CML cells into the cell cycle was decreased relative to cells from normal donors, and greater heterogeneity in the phenotype of CML cells at the initiation of culture was observed. Analysis of phenotype concomitant with cell division also demonstrated that the differentiation of normal CD34+ cells was consistent between donors, while marked variability was observed in the differentiation of CD34+ cells from CML patients. This included expression of CD13, CD33, CD38 and HLA-DR, which were linked to cell division in normal but not CML cells. The tyrosine kinase inhibitor, imatinib, is a novel drug displaying promising results in the treatment of CML by specifically inhibiting the growth of leukaemic cells. To examine whether myelosuppression observed in patients treated with imatinib may arise from inhibition of normal haemopoiesis, imatinib was added to colony assays established using cells from normal bone marrow. Suppression of monocyte/macrophage growth, but not that of eosinophils or neutrophils, was observed at therapeutic concentrations of imatinib. Inhibition of monocytic differentiation to macrophages was also observed and was associated with decreased functional capacity such as altered antigen uptake, production of proinflammatory cytokines and stimulation of responder cells. The specific suppression of monocyte/macrophage differentiation and function was not due to blockade of tyrosine kinases known to be inhibited by imatinib and was consistent with an inhibition of the M-CSF/c-fms signalling pathway. This hypothesis was tested using a cell line that was dependent on M-CSF for growth and survival. Cell proliferation and phosphorylation of c-fms were inhibited at an IC50 of 1.9μM and 1.4μM imatinib respectively and this was not attributable to decreased c-fms expression. These important findings therefore identify c-fms as a further target of imatinib, and suggest that imatinib should be considered for treatment of diseases where c-fms is implicated. This includes breast and ovarian cancer and inflammatory conditions such as rheumatoid arthritis. Potential side effects resulting from imatinib treatment must also be considered. / Thesis (Ph.D.)--School of Medicine, 2004.

Introduction Bacterial biofilms have been implicated in the pathogenesis of Chronic Rhinosinusitis (CRS). This thesis consists of a number of separate studies. The results of each study were designed to help provide an evolution of knowledge that could be applied to our subsequent investigations on the topic of bacterial biofilms and chronic rhinosinusitis. In vitro studies were utilized to document the capacity of CRS bacteria to form biofilms as well as to investigate the efficacy of various antimicrobials at high concentrations. Additionally, an in vivo sheep model was developed to examine different biofilm detection techniques. Finally, a study of CRS patients was conducted to investigate the incidence of biofilm related sinus disease. Methods Our in vitro studies used 96 well crystal violet microtiter plate assays to determine the biofilm growth characteristics of S.aureus isolated from patients with CRS. Established biofilms were then subjected various antimicrobial agents, and the degree of biofilm reduction calculated to examine their potential for sinus biofilm treatment. A sheep sinusitis model involved performing endoscopic sinus surgery, occlusion of frontal sinus ostia and the introduction of bacteria. Mucosal specimens were subsequently examined for the presence of bacterial biofilms using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). CSLM was also used in a prospective study to document the presence bacterial biofilms on the mucosa of patients with CRS compared to controls. Results The findings of in vitro experiments revealed that not all isolates were capable of forming biofilms. Of the antibiotics tested, only Mupirocin was capable of reducing biofilm mass by 90% in all isolates. The animal model showed considerable variation in biofilm detection rates. The CSLM biofilm detection rate was 100% in obstructed sinuses with bacteria introduced, whereas TEM detected only 66%. Both these objective measures failed to identify biofilms in control groups. SEM found biofilms in all experimental groups including controls. CSLM analysis of CRS patients found Bacterial biofilms in 44% and no biofilms in controls. Conclusion The demonstration of biofilms in the sheep model for sinusitis and biofilms on the mucosal specimens of patients with CRS, and the ability of bacteria in CRS to form biofilms in vitro, further supports the hypothesis that biofilms play a role in the pathogenesis of CRS. CSLM is the modality of choice in documenting the presence of bacterial biofilms on sinus mucosal surfaces due to the inherent flaws of sampling error and subjectivity of TEM and SEM. Finally, CRS is a multi-factorial disease, topical Mupirocin via nasal irrigation may be a therapeutic option in patients with likely S.aureus biofilms. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1367183 / Thesis (M.S.) - University of Adelaide, School of Medicine, 2009