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.

Selecting, optimizing and fusing ‘salient’ Gabor features for facial expression recognition

This paper describes a novel framework for facial expression recognition from still images by selecting, optimizing and fusing ‘salient’ Gabor feature layers to recognize six universal facial expressions using the K nearest neighbor classifier. The recognition comparisons with all layer approach using JAFFE and Cohn-Kanade (CK) databases confirm that using ‘salient’ Gabor feature layers with optimized sizes can achieve better recognition performance and dramatically reduce computational time. Moreover, comparisons with the state of the art performances demonstrate the effectiveness of our approach.

Library technician course recognition : meeting the challenge of a distributed national education program

This paper looks at the challenges presented for the Australian Library and Information Association by its role as the professional association responsible for ensuring the quality of Australian library technician graduates. There is a particular focus on the issue of course recognition, where the Association's role is complicated by the need to work alongside the national quality assurance processes that have been established by the relevant technical education authorities. The paper describes the history of course recognition in Australia; examines the relationship between course recognition and other quality measures; and describes the process the Association has undertaken recently to ensure appropriate professional scrutiny in a changing environment of accountability.

Risk-assessment practices in the private rental sector : implications for low-income renters (Final Report)

This report focuses on risk-assessment practices in the private rental market, with particular consideration of their impact on low-income renters. It is based on the fieldwork undertaken in the second stage of the research process that followed completion of the Positioning Paper. The key research question this study addressed was: What are the various factors included in ‘risk-assessments’ by real estate agents in allocating ‘affordable’ tenancies? How are these risks quantified and managed? What are the key outcomes of their decision-making? The study builds on previous research demonstrating that a relatively large proportion of low-cost private rental accommodation is occupied by moderate- to high-income households (Wulff and Yates 2001; Seelig 2001; Yates et al. 2004). This is occurring in an environment where the private rental sector is now the de facto main provider of rental housing for lower-income households across Australia (Seelig et al. 2005) and where a number of factors are implicated in patterns of ‘income–rent mismatching’. These include ongoing shifts in public housing assistance; issues concerning eligibility for rent assistance; ‘supply’ factors, such as loss of low-cost rental stock through upgrading and/or transfer to owner-occupied housing; patterns of supply and demand driven largely by middle- to high-income owner-investors and renters; and patterns of housing need among low-income households for whom affordable housing is not appropriate. In formulating a way of approaching the analysis of ‘risk-assessment’ in rental housing management, this study has applied three sociological perspectives on risk: Beck’s (1992) formulation of risk society as entailing processes of ‘individualisation’; a socio-cultural perspective which emphasises the situated nature of perceptions of risk; and a perspective which has drawn attention to different modes of institutional governance of subjects, as ‘carriers of specific indicators of risk’. The private rental market was viewed as a social institution, and the research strategy was informed by ‘institutional ethnography’ as a method of enquiry. The study was based on interviews with property managers, real estate industry representatives, tenant advocates and community housing providers. The primary focus of inquiry was on ‘the moment of allocation’. Six local areas across metropolitan and regional Queensland, New South Wales, and South Australia were selected as case study localities. In terms of the main findings, it is evident that access to private rental housing is not just a matter of ‘supply and demand’. It is also about assessment of risk among applicants. Risk – perceived or actual – is thus a critical factor in deciding who gets housed, and how. Risk and its assessment matter in the context of housing provision and in the development of policy responses. The outcomes from this study also highlight a number of salient points: 1.There are two principal forms of risk associated with property management: financial risk and risk of litigation. 2. Certain tenant characteristics and/or circumstances – ability to pay and ability to care for the rented property – are the main factors focused on in assessing risk among applicants for rental housing. Signals of either ‘(in)ability to pay’ and/or ‘(in)ability to care for the property’ are almost always interpreted as markers of high levels of risk. 3. The processing of tenancy applications entails a complex and variable mix of formal and informal strategies of risk-assessment and allocation where sorting (out), ranking, discriminating and handing over characterise the process. 4. In the eyes of property managers, ‘suitable’ tenants can be conceptualised as those who are resourceful, reputable, competent, strategic and presentable. 5. Property managers clearly articulated concern about risks entailed in a number of characteristics or situations. Being on a low income was the principal and overarching factor which agents considered. Others included: - unemployment - ‘big’ families; sole parent families - domestic violence - marital breakdown - shift from home ownership to private rental - Aboriginality and specific ethnicities - physical incapacity - aspects of ‘presentation’. The financial vulnerability of applicants in these groups can be invoked, alongside expressed concerns about compromised capacities to manage income and/or ‘care for’ the property, as legitimate grounds for rejection or a lower ranking. 6. At the level of face-to-face interaction between the property manager and applicants, more intuitive assessments of risk based upon past experience or ‘gut feelings’ come into play. These judgements are interwoven with more systematic procedures of tenant selection. The findings suggest that considerable ‘risk’ is associated with low-income status, either directly or insofar as it is associated with other forms of perceived risk, and that such risks are likely to impede access to the professionally managed private rental market. Detailed analysis suggests that opportunities for access to housing by low-income householders also arise where, for example: - the ‘local experience’ of an agency and/or property manager works in favour of particular applicants - applicants can demonstrate available social support and financial guarantors - an applicant’s preference or need for longer-term rental is seen to provide a level of financial security for the landlord - applicants are prepared to agree to specific, more stringent conditions for inspection of properties and review of contracts - the particular circumstances and motivations of landlords lead them to consider a wider range of applicants - In particular circumstances, property managers are prepared to give special consideration to applicants who appear worthy, albeit ‘risky’. The strategic actions of demonstrating and documenting on the part of vulnerable (low-income) tenant applicants can improve their chances of being perceived as resourceful, capable and ‘savvy’. Such actions are significant because they help to persuade property managers not only that the applicant may have sufficient resources (personal and material) but that they accept that the onus is on themselves to show they are reputable, and that they have valued ‘competencies’ and understand ‘how the system works’. The parameters of the market do shape the processes of risk-assessment and, ultimately, the strategic relation of power between property manager and the tenant applicant. Low vacancy rates and limited supply of lower-cost rental stock, in all areas, mean that there are many more tenant applicants than available properties, creating a highly competitive environment for applicants. The fundamental problem of supply is an aspect of the market that severely limits the chances of access to appropriate and affordable housing for low-income rental housing applicants. There is recognition of the impact of this problem of supply. The study indicates three main directions for future focus in policy and program development: providing appropriate supports to tenants to access and sustain private rental housing, addressing issues of discrimination and privacy arising in the processes of selecting suitable tenants, and addressing problems of supply.

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.

Scatter difference NAP for SVM speaker recognition

This paper presents Scatter Difference Nuisance Attribute Projection (SD-NAP) as an enhancement to NAP for SVM-based speaker verification. While standard NAP may inadvertently remove desirable speaker variability, SD-NAP explicitly de-emphasises this variability by incorporating a weighted version of the between-class scatter into the NAP optimisation criterion. Experimental evaluation of SD-NAP with a variety of SVM systems on the 2006 and 2008 NIST SRE corpora demonstrate that SD-NAP provides improved verification performance over standard NAP in most cases, particularly at the EER operating point.

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.

Augmenting web service discovery by cognitive semantics and abduction

We argue that web service discovery technology should help the user navigate a complex problem space by providing suggestions for services which they may not be able to formulate themselves as (s)he lacks the epistemic resources to do so. Free text documents in service environments provide an untapped source of information for augmenting the epistemic state of the user and hence their ability to search effectively for services. A quantitative approach to semantic knowledge representation is adopted in the form of semantic space models computed from these free text documents. Knowledge of the user’s agenda is promoted by associational inferences computed from the semantic space. The inferences are suggestive and aim to promote human abductive reasoning to guide the user from fuzzy search goals into a better understanding of the problem space surrounding the given agenda. Experimental results are discussed based on a complex and realistic planning activity.

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.

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.