Re-invent yourself: from London intensive care nursing and the Nigerian oil fields to an an academic library in Brisbane; a career change worth making.

A complete change of career forces a seismic shift in every aspect of your life. From day one, you have to face the loss of long held beliefs, behaviours, the known world of self, and security. We came from professions that themselves are poles apart, and many of the challenges we faced entering the profession were the same: juggling full-time work, part time study, and family commitmemts, taking a pay cut, and loss of social life. But over a short period of time we both transitioned to our new profession successfully. so what make our successful transition possible?

Development of a colorimetric assay for heparanase activity suitable for kinetic analysis and inhibitor screening

The role that heparanase plays during metastasis and angiogenesis in tumors makes it an attractive target for cancer therapeutics. Despite this enzyme’s significance, most of the assays developed to measure its activity are complex. Moreover, they usually rely on labeling variable preparations of the natural substrate heparan sulfate, making comparisons across studies precarious. To overcome these problems, we have developed a convenient assay based on the cleavage of the synthetic heparin oligosaccharide fondaparinux. The assay measures the appearance of the disaccharide product of heparanase-catalyzed fondaparinux cleavage colorimetrically using the tetrazolium salt WST-1. Because this assay has a homogeneous substrate with a single point of cleavage, the kinetics of the enzyme can be reliably characterized, giving a Km of 46 μM and a kcat of 3.5 s−1 with fondaparinux as substrate. The inhibition of heparanase by the published inhibitor, PI-88, was also studied, and a Ki of 7.9 nM was determined. The simplicity and robustness of this method, should, not only greatly assist routine assay of heparanase activity but also could be adapted for high-throughput screening of compound libraries, with the data generated being directly comparable across studies.

My place through my eyes : a social constructionist approach to researching the relationships between socioeconomic living contexts and physical activity

There is a growing evidence-base in the epidemiological literature that demonstrates significant associations between people’s living circumstances – including their place of residence – and their health-related practices and outcomes (Leslie, 2005; Karpati, Bassett, & McCord, 2006; Monden, Van Lenthe, & Mackenbach, 2006; Parkes & Kearns, 2006; Cummins, Curtis, Diez-Roux, & Macintyre, 2007; Turrell, Kavanagh, Draper, & Subramanian, 2007). However, these findings raise questions about the ways in which living places, such as households and neighbourhoods, figure in the pathways connecting people and health (Frolich, Potvin, Chabot, & Corin, 2002; Giles-Corti, 2006; Brown et al, 2006; Diez Roux, 2007). This thesis addressed these questions via a mixed methods investigation of the patterns and processes connecting people, place, and their propensity to be physically active. Specifically, the research in this thesis examines a group of lower-socioeconomic residents who had recently relocated from poorer suburbs to a new urban village with a range of health-related resources. Importantly, the study contrasts their historical relationship with physical activity with their reactions to, and everyday practices in, a new urban setting designed to encourage pedestrian mobility and autonomy. The study applies a phenomenological approach to understanding living contexts based on Berger and Luckman’s (1966) conceptual framework in The Social Construction of Reality. This framework enables a questioning of the concept of context itself, and a treatment of it beyond environmental factors to the processes via which experiences and interactions are made meaningful. This approach makes reference to people’s histories, habituations, and dispositions in an exploration between social contexts and human behaviour. This framework for thinking about context is used to generate an empirical focus on the ways in which this residential group interacts with various living contexts over time to create a particular construction of physical activity in their lives. A methodological approach suited to this thinking was found in Charmaz’s (1996; 2001; 2006) adoption of a social constructionist approach to grounded theory. This approach enabled a focus on people’s own constructions and versions of their experiences through a rigorous inductive method, which provided a systematic strategy for identifying patterns in the data. The findings of the study point to factors such as ‘childhood abuse and neglect’, ‘early homelessness’, ‘fear and mistrust’, ‘staying indoors and keeping to yourself’, ‘conflict and violence’, and ‘feeling fat and ugly’ as contributors to an ongoing core category of ‘identity management’, which mediates the relationship between participants’ living contexts and their physical activity levels. It identifies barriers at the individual, neighbourhood, and broader ecological levels that prevent this residential group from being more physically active, and which contribute to the ways in which they think about, or conceptualise, this health-related behaviour in relationship to their identity and sense of place – both geographic and societal. The challenges of living well and staying active in poorer neighbourhoods and in places where poverty is concentrated were highlighted in detail by participants. Participants’ reactions to the new urban neighbourhood, and the depth of their engagement with the resources present, are revealed in the context of their previous life-experiences with both living places and physical activity. Moreover, an understanding of context as participants’ psychological constructions of various social and living situations based on prior experience, attitudes, and beliefs was formulated with implications for how the relationship between socioeconomic contextual effects on health are studied in the future. More detailed findings are presented in three published papers with implications for health promotion, urban design, and health inequalities research. This thesis makes a substantive, conceptual, and methodological contribution to future research efforts interested in how physical activity is conceptualised and constructed within lower socioeconomic living contexts, and why this is. The data that was collected and analysed for this PhD generates knowledge about the psychosocial processes and mechanisms behind the patterns observed in epidemiological research regarding socioeconomic health inequalities. Further, it highlights the ways in which lower socioeconomic living contexts tend to shape dispositions, attitudes, and lifestyles, ultimately resulting in worse health and life chances for those who occupy them.

Preventing physical activity induced heat illness in school settings

The climatic conditions of tropical and subtropical regions within Australia present, at times, extreme risk of physical activity induced heat illness. Many administrators and teachers in school settings are aware of the general risks of heat related illness. In the absence of reliable information applied at the local level, there is a risk that inappropriate decisions may be made concerning school events that incorporate opportunities to be physically active. Such events may be prematurely cancelled resulting in the loss of necessary time for physical activity. Under high or extremely high risk conditions however, the absence of appropriate modifications or continuation could place the health of students, staff and other parties at risk. School staff and other key stakeholders should understand the mechanisms of escalating risk and be supported to undertake action to reduce the level of risk through appropriate policies, procedures, resources and action plans.

Seasonal activity and abundance of Orosius orientalis (Hemiptera : Cicadellidae) at agricultural sites in Southeastern Australia

Orosius orientalis is a leafhopper vector of several viruses and phytoplasmas affecting a broad range of agricultural crops. Sweep net, yellow pan trap and yellow sticky trap collection techniques were evaluated. Seasonal distribution of O. orientalis was surveyed over two successive growing seasons around the borders of commercially grown tobacco crops. Orosius orientalis seasonal activity as assessed using pan and sticky traps was characterised by a trimodal peak and relative abundance as assessed using sweep nets differed between field sites with peak activity occurring in spring and summer months. Yellow pan traps consistently trapped a higher number of O. orientalis than yellow sticky traps.

Exercise and activity – how it helps lymphoedema?

Research investigating the role of exercise in the prevention and/or management of lymphoedema is lacking. For fear of initiating or exacerbating lymphoedema, and its associated symptoms, those with lymphoedema have traditionally been cautioned against engaging in physical activity rather than encouraged to be regularly active. However, recent preliminary findings suggest that being inactive may increase risk of developing lymphedema, and that for those with lymphoedema, participation in an exercise program does not exacerbate the condition. This presentation will address why engaging in regular physical activity is important, what we know about the role of exercise with respect to lymphoedema prevention and management, and will provide some practical recommendations about becoming and staying regularly active for those with lymphoedema.

Relationship over time between psychological distress and physical activity in colorectal cancer survivors

Purpose Increased physical activity in colorectal cancer patients is related to improved recurrence free and overall survival. Psychological distress after cancer may place patients at risk of reduced physical activity; but paradoxically also act as a motivator for positive lifestyle change. The relationship between psychological distress and physical activity after cancer over time has not been described. Methods A prospective survey of 1966 (57% response) colorectal cancer survivors assessed the psychological distress variables of anxiety, depression, somatisation, cancer threat appraisal as predictors of physical activity five, 12, 24 and 36 months post-diagnosis 978 respondents had valid data for all time points. Results Higher somatisation was associated with greater physical inactivity (Relative risk ratio (RRR) =1.12; 95% CI=[1.1, 1.2]) and insufficient physical activity (RRR=1.05; [0.90, 1.0]). Respondents with a more positive appraisal of their cancer were significantly (p=0.031) less likely to be inactive (RRR=0.95; [0.90, 1.0]) or insufficiently active (RRR=0.96). Fatigued and obese respondents and current smokers were more inactive. Respondents whose somatisation increased between two time periods were less likely to increase their physical activity over the same period (p<0.001). Respondents with higher anxiety at one time period were less likely to have increased their activity at the next assessment (p=0.004). There was no association between depression and physical activity. Conclusions Cancer survivors who experience somatisation and anxiety are at greater risk of physical inactivity. The lack of a clear relationship between higher psychological distress and increasing physical activity argues against distress as a motivator to exercise in these patients.

Anti-cancer activity of zoledronic acid in breast cancer

Background: Zoledronic acid is used to prevent the bone loss associated with antioestrogen treatments in subjects with breast cancer. Preclinical studies suggest that zoledronic acid may have anticancer activity in its own right. This anticancer possibility with zoledronic acid has not been investigated extensively in clinical trials. Objectives/methods: This evaluation is of a large clinical trial that investigated the effect of zoledronic acid on cancer outcomes in premenopausal women with breast cancer. Results: The trial showed that after 4 years, 94.0% of subjects who were treated with zoledronic acid were disease-free compared with 90.8% of those not treated with zoledronic acid. Recurrence survival was a secondary end point; this occurred in 94.0% with, and 90.9% without, zoledronic acid treatment. Conclusions: Zoledronic acid does have anticancer activity in premenopausal women with cancer.

Radiological aspects of petroleum exploration and production in the sultanate of Oman

This thesis is a study of naturally occurring radioactive materials (NORM) activity concentration, gamma dose rate and radon (222Rn) exhalation from the waste streams of large-scale onshore petroleum operations. Types of activities covered included; sludge recovery from separation tanks, sludge farming, NORM storage, scaling in oil tubulars, scaling in gas production and sedimentation in produced water evaporation ponds. Field work was conducted in the arid desert terrain of an operational oil exploration and production region in the Sultanate of Oman. The main radionuclides found were 226Ra and 210Pb (238U - series), 228Ra and 228Th (232Th - series), and 227Ac (235U - series), along with 40K. All activity concentrations were higher than the ambient soil level and varied over several orders of magnitude. The range of gamma dose rates at a 1 m height above ground for the farm treated sludge had a range of 0.06 0.43 µSv h 1, and an average close to the ambient soil mean of 0.086 ± 0.014 µSv h 1, whereas the untreated sludge gamma dose rates had a range of 0.07 1.78 µSv h 1, and a mean of 0.456 ± 0.303 µSv h 1. The geometric mean of ambient soil 222Rn exhalation rate for area surrounding the sludge was mBq m 2 s 1. Radon exhalation rates reported in oil waste products were all higher than the ambient soil value and varied over three orders of magnitude. This study resulted in some unique findings including: (i) detection of radiotoxic 227Ac in the oil scales and sludge, (ii) need of a new empirical relation between petroleum sludge activity concentrations and gamma dose rates, and (iii) assessment of exhalation of 222Rn from oil sludge. Additionally the study investigated a method to determine oil scale and sludge age by the use of inherent behaviour of radionuclides as 228Ra:226Ra and 228Th:228Ra activity ratios.

Measurement properties of the Australian Women's Activity Survey

Purpose: The Australian Women’s Activity Survey (AWAS) was developed based on a systematic review and qualitative research on how to measure activity patterns of women with young children (WYC). AWAS assesses activity performed across five domains (planned activities, employment, childcare, domestic responsibilities and transport), and intensity levels (sitting, light-intensity, brisk walking, moderate-intensity and vigorous-intensity) in a typical week in the past month. The purpose of this study was to assess the test-retest reliability and criterion validity of the AWAS. Methods: WYC completed the AWAS on two occasions 7-d apart (test-retest reliability protocol) and/or wore an MTI ActiGraph accelerometer for 7-d in between (validity protocol). Forty WYC (mean age 35 ± 5yrs) completed the test-retest reliability protocol and 75 WYC (mean age 33 ± 5yrs) completed the validity protocol. Interclass Correlation Coefficients (ICC) between AWAS administrations and Spearman’s Correlation Coefficients (rs) between AWAS and MTI data were calculated. Results: AWAS showed good test-retest reliability (ICC=0.80 (0.65-0.89)) and acceptable criterion validity (rs= 0.28, p=0.01) for measuring weekly health-enhancing physical activity. AWAS also provided repeatable and valid estimates of sitting time (test-retest reliability ICC=0.42 (0.13-0.64), and criterion validity (rs= 0.32, p=0.006)). Conclusion: The measurement properties of the AWAS are comparable to those reported for existing self-report measures of physical activity. However, AWAS offers a more comprehensive and flexible alternative for accurately assessing different domains and intensities of activity relevant to WYC. Future research should investigate whether the AWAS is a suitable measure of intervention efficacy by examining its sensitivity to change.

Cost-effectiveness of a telephone-delivered intervention for physical activity and diet

Background: Given escalating rates of chronic disease, broad-reach and cost-effective interventions to increase physical activity and improve dietary intake are needed. The cost-effectiveness of a Telephone Counselling intervention to improve physical activity and diet, targeting adults with established chronic diseases in a low socio-economic area of a major Australian city was examined. Methodology/Principal Findings: A cost-effectiveness modelling study using data collected between February 2005 and November 2007 from a cluster-randomised trial that compared Telephone Counselling with a “Usual Care” (brief intervention) alternative. Economic outcomes were assessed using a state-transition Markov model, which predicted the progress of participants through five health states relating to physical activity and dietary improvement, for ten years after recruitment. The costs and health benefits of Telephone Counselling, Usual Care and an existing practice (Real Control) group were compared. Telephone Counselling compared to Usual Care was not cost-effective ($78,489 per quality adjusted life year gained). However, the Usual Care group did not represent existing practice and is not a useful comparator for decision making. Comparing Telephone Counselling outcomes to existing practice (Real Control), the intervention was found to be cost-effective ($29,375 per quality adjusted life year gained). Usual Care (brief intervention) compared to existing practice (Real Control) was also cost-effective ($12,153 per quality adjusted life year gained). Conclusions/Significance: This modelling study shows that a decision to adopt a Telephone Counselling program over existing practice (Real Control) is likely to be cost-effective. Choosing the ‘Usual Care’ brief intervention over existing practice (Real Control) shows a lower cost per quality adjusted life year, but the lack of supporting evidence for efficacy or sustainability is an important consideration for decision makers. The economics of behavioural approaches to improving health must be made explicit if decision makers are to be convinced that allocating resources toward such programs is worthwhile.

Remote interaction and user research : anaesthetic preadmission activity

In the absence of telehealth technology, rural patients must travel to a regional or metropolitan hospital for a preadmission consultation one week before their surgery. Currently, examination of the patient’s chest using a stethoscope (auscultation) is not possible over a telehealth network as existing digital stethoscopes have been designed for in-person auscultation. We report on the initial phase of research which ultimately aims to design a digital stethoscope for use in the telehealth context. This initial research phase describes the complexity of the activity of preadmission clinics and the implications for the design of the stethoscope. The research is conducted through field studies of existing face-to-face and remote consultations.

Passenger experience in an airport : an activity-centred approach

An airport is one of the largest and most complex systems in modern society. Observational field studies have been conducted to investigate passenger experiences in, and interactions within, an international airport. Based on these studies, this paper discusses how activities mediate people’s experiences in the airport. For example, moving through the security screening process is discussed from both passenger and staff perspectives. The applied coding scheme ensured research rigor. The findings illustrate that passenger activities are complex and shared, and only partially supported by current terminal design. Thus, this research has the potential to impact on airport design to facilitate passenger flow through airport precincts.

New insights into appetite, inflammation and the use of fish oil in hemodialysis patients

Protein-energy wasting (PEW) is commonly seen in patients with chronic kidney disease (CKD). The condition is characterised by chronic, systemic low-grade inflammation which affects nutritional status by a variety of mechanisms including reducing appetite and food intake and increasing muscle catabolism. PEW is linked with co-morbidities such as cardiovascular disease, and is associated with lower quality of life, increased hospitalisations and a 6-fold increase in risk of death1. Significant gender differences have been found in the severity and effects of several markers of PEW. There have been limited studies testing the ability of anti-inflammatory agents or nutritional interventions to reduce the effects of PEW in dialysis patients. This thesis makes a significant contribution to the understanding of PEW in dialysis patients. It advances understanding of measurement techniques for two of the key components, appetite and inflammation, and explores the effect of fish oil, an anti-inflammatory agent, on markers of PEW in dialysis patients. The first part of the thesis consists of two methodological studies conducted using baseline data. The first study aims to validate retrospective ratings of hunger, desire to eat and fullness on visual analog scales (VAS) (paper and pen and electronic) as a new method of measuring appetite in dialysis patients. The second methodological study aims to assess the ability of a variety of methods available in routine practice to detect the presence of inflammation. The second part of the thesis aims to explore the effect of 12 weeks supplementation with 2g per day of Eicosapentaenoic Acid (EPA), a longchain fatty acid found in fish oil, on markers of PEW. A combination of biomarkers and psychomarkers of appetite and inflammation are the main outcomes being explored, with nutritional status, dietary intake and quality of life included as secondary outcomes. A lead in phase of 3 months prior to baseline was used so that each person acts as their own historical control. The study also examines whether there are gender differences in response to the treatment. Being an exploratory study, an important part of the work is to test the feasibility of the intervention, thus the level of adherence and factors associated with adherence are also presented. The studies were conducted at the hemodialysis unit of the Wesley Hospital. Participants met the following criteria: adult, stage 5 CKD on hemodialysis for at least 3 months, not expected to receive a transplant or switch to another dialysis modality during the study, absence of intellectual impairment or mental illness impairing ability to follow instructions or complete the intervention. A range of intermediate, clinical and patient-centred outcome measures were collected at baseline and 12 weeks. Inflammation was measured using five biomarkers: c-reactive protein (CRP), interleukin-6 (IL6), intercellular adhesion molecule (sICAM-1), vascular cell adhesion molecule (sVCAM-1) and white cell count (WCC). Subjective appetite was measured using the first question from the Appetite and Dietary Assessment (ADAT) tool and VAS for measurements of hunger, desire to eat and fullness. A novel feature of the study was the assessment of the appetite peptides leptin, ghrelin and peptide YY as biomarkers of appetite. Nutritional status/inflammation was assessed using the Malnutrition-Inflammation Score (MIS) and the Patient-Generated Subjective Global Assessment (PG-SGA). Dietary intake was measured using 3-day records. Quality of life was measured using the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF™ v1.3 © RAND University), which combines the Short-Form 36 (SF36) with a kidney-disease specific module2. A smaller range of these variables was available for analysis during the control phase (CRP, ADAT, dietary intake and nutritional status). Statistical analysis was carried out using SPSS version 14 (SPSS Inc, Chicago IL, USA). Analysis of the first part of the thesis involved descriptive and bivariate statistics, as well as Bland-Altman plots to assess agreement between methods, and sensitivity analysis/ROC curves to test the ability of methods to predict the presence of inflammation. The unadjusted (paired ttests) and adjusted (linear mixed model) change over time is presented for the main outcome variables of inflammation and appetite. Results are shown for the whole group followed by analyses according to gender and adherence to treatment. Due to the exploratory nature of the study, trends and clinical significance were considered as important as statistical significance. Twenty-eight patients (mean age 61±17y, 50% male, dialysis vintage 19.5 (4- 101) months) underwent baseline assessment. Seven out of 28 patients (25%) reported sub-optimal appetite (self-reported as fair, poor or very poor) despite all being well nourished (100% SGA A). Using the VAS, ratings of hunger, but not desire to eat or fullness, were significantly (p<0.05) associated with a range of relevant clinical variables including age (r=-0.376), comorbidities (r=-0.380) nutritional status (PG-SGA score, r=-0.451), inflammatory markers (CRP r=-0.383; sICAM-1 r=-0.387) and seven domains of quality of life. Patients expressed a preference for the paper and pen method of administering VAS. None of the tools (appetite, MIS, PG-SGA, albumin or iron) showed an acceptable ability to detect patients who are inflamed. It is recommended that CRP should be tested more frequently as a matter of course rather than seeking alternative methods of measuring inflammation. 27 patients completed the 12 week intervention. 20 patients were considered adherent based on changes in % plasma EPA, which rose from 1.3 (0.94)% to 5.2 (1.1)%, p<0.001, in this group. The major barriers to adherence were forgetting to take the tablets as well as their size. At 12 weeks, inflammatory markers remained steady apart from the white cell count which decreased (7.6(2.5) vs 7.0(2.2) x109/L, p=0.058) and sVCAM-1 which increased (1685(654) vs 2249(925) ng/mL, p=0.001). Subjective appetite using VAS increased (51mm to 57mm, +12%) and there was a trend towards reduction in peptide YY (660(31) vs 600(30) pg/mL, p=0.078). There were some gender differences apparent, with the following adjusted change between baseline and week 12: CRP (males -3% vs females +17%, p=0.19), IL6 (males +17% vs females +48%, p=0.77), sICAM-1 (males -5% vs females +11%, p=0.07), sVCAM-1 (males +54% vs females +19%, p=0.08) and hunger ratings (males 20% vs females -5%, p=0.18). On balance, males experienced a maintainence or reduction in three inflammatory markers and an improvement in hunger ratings, and therefore appeared to have responded better to the intervention. Compared to those who didn’t adhere, adherent patients maintained weight (mean(SE) change: +0.5(1.6) vs - 0.8(1.2) kg, p=0.052) and fat-free mass (-0.1 (1.6) vs -1.8 (1.8) kg, p=0.045). There was no difference in change between the intervention and control phase for CRP, appetite, nutritional status or dietary intake. The thesis makes a significant contribution to the evidence base for understanding of PEW in dialysis patients. It has advanced knowledge of methods of assessing inflammation and appetite. Retrospective ratings of hunger on a VAS appear to be a valid method of assessing appetite although samples which include patients with very poor appetite are required to confirm this. Supplementation with fish oil appeared to improve subjective appetite and dampen the inflammatory response. The effectiveness of the intervention is influenced by gender and adherence. Males appear to be more responsive to the primary outcome variables than females, and the quality of response is improved with better adherence. These results provide evidence to support future interventions aimed at reducing the effects of PEW in dialysis patients.