Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients

Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM). Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome. To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins. This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2). Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models. The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.

Victims’ perceptions of traditional and cyberbullying, and the psychosocial correlates of their victimisation

It is well recognised that there are serious correlates for victims of traditional bullying. These have been shown to include increased levels of depression, anxiety and psychosomatic symptoms, in addition to often severe physical harm and even suicide. Bullied students also feel more socially ineffective; have greater interpersonal difficulties, together with higher absenteeism from school and lower academic competence. In the emerging field of cyberbullying many researchers have hypothesised a greater impact and more severe consequences for victims because of the 24/7 nature and the possibility of the wider audience with this form of bullying. However, to date there is scarce empirical evidence to support this. This study sought to compare victims’ perceptions of the harshness and impact of bullying by traditional and cyber means. The major findings showed that although students who had been victimised by traditional bullying reported that they felt their bullying was harsher, crueller and had more impact on their lives than those students who had been cyberbullied, the correlates of their mental health revealed that cyber victims reported significantly more social difficulties, higher anxiety levels and depression than traditional victims. The implications for school counsellors and mental health workers are discussed.

The experiences of parents and other supervisors in a graduated driver licensing program in Queensland, Australia

Study Aims Describe how parents and other private supervisors have responded to the changes made to the Queensland graduated driver licensing system in mid-2007 Examine differences in the experiences and perceptions of the parents and non-parents Method Combination of convenience and snowball sampling Survey administered by the internet Survey conducted between July 2009 and May 2010 Approximately 15-20 minutes to complete $20 reimbursement for participation

Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine : involvement of adenosine and dopamine receptors

Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.

Benefits and challenges of using restorative justice approaches for victims of crime committed by adults: An exploration of theory and evidence

Book Abstract: Current experimentations with approaches to restorative justice for adult offenders represents a compelling new direction in the criminal justice system. This book examines the values and challenges of restorative justice for adult offenders, victims and communities. The discussion is situated within current debate, available research, and the international literature. In canvassing the structure, content, and delivery of key Australian and New Zealand restorative justice programs for adult offenders, the distinguished authors offer critical analysis of the emergence and impact of program developements for practitioners and professionals. This collection brings together stimulating and informed articles by experienced practitioners, leading academics and new researchers in the field. It also offers valuable insights into emerging restorative justice practice for adult offenders and provides a real alternative to the adversarial justice system.

The gender wage gap : a comparison of Australia and Canada

Using data from the 1989 Canadian Labour Market Activity Survey and, for Australia, the 1989-90 Income Distribution Survey, the authors investigate the reasons for the significantly lower gender wage gap in Australia than in Canada. Key similarities and differences between these two countries, the authors argue, make them a good basis for a "natural experiment" to investigate the effects of different labor market institutions. In particular, Australia has a stronger union movement and a greater degree of centralization in wage determination than Canada, and most of its workers are covered by legally binding minimum working conditions. The authors conclude that several differences between the countries in labor market structure-notably, a lower rate of return to education, a lower rate of return to labor market experience, and a lower level of wage inequality in Australia than in Canada- are largely responsible for the smaller gender wage gap in Australia.

Young people whose parents are separated or divorced: A case for researching their experiences at the intersection of home and school

Background: Young people whose parents are separated or divorced form a significant and increasing proportion of young people who attend school. To date, empirical research with young people whose parents are separated or divorced has tended to focus on either their household context, or their school context, rather than on both contexts together. This paper redresses this singular focus by examining the intersection of the experiences of young people at both home and school. Purpose: The paper seeks to map the empirical evidence of young people's home and school experiences as they move between households and schools. Sources of evidence: The paper provides a narrative review of the literature from the 1990s to the present, locating Australian research within an international context. The review is framed by four main questions. What is the impact upon young people of the family transitions that occur when parents separate or divorce? What is the everyday impact upon young people of moving between one household and another? What does the research reveal regarding educational, social and emotional outcomes for this group? What does the research reveal regarding their school experiences? Main argument: The review reveals a paucity of Australian research at the intersection of home and school. It shows that, while young people from these contexts form a growing proportion of the school population, there is little empirical evidence of what is actually occurring in their everyday lives. The review reveals the importance of researching from the perspectives of the young people themselves. Conclusions: Evidence provided in the paper shows that many young people whose parents separate or divorce are affected socially, emotionally and educationally. Such evidence points to the need for research into the everyday experiences of the young people at school, in order to identify, from their perspective, how schools can better cater for these young people and their families.

Revised reinforcement sensitivity theory : the impact of FFFS and stress on driving

This study investigated the effect of a fear-based personality trait, as conceptualised in Gray’s revised reinforcement sensitivity theory (RST) by the strength of the fight/flight/freeze system (FFFS), on young people’s driving simulator performance under induced psychosocial stress. Seventy-one young drivers completed the Jackson-5 questionnaire of RST traits, followed by a psychosocial stress or relaxation induction procedure (random allocation to groups) and then a city driving simulator task. Some support was found for the hypothesis that higher FFFS sensitivity would result in poorer driving performance under stress, in terms of significantly poorer hazard responses, possibly due to an increased attentional focus on the aversive cues inherent in the stress induction leaving reduced attentional capacity for the driving task. These results suggest that stress may lead to riskier driving behaviour in individuals with fearful RST personality styles.

Vaccination of healthy and diseased koalas (Phascolarctos cinereus) with a Chlamydia pecorum multi-subunit vaccine : evaluation of immunity and pathology

Chlamydial infections represent a major threat to the long-term survival of the koala and a successful vaccine would provide a valuable management tool. Vaccination however has the potential to enhance inflammatory disease in animals exposed to a natural infection prior to vaccination, a finding in early human and primate trials of whole cell vaccines to prevent trachoma. In the present study, we vaccinated both healthy koalas as well as clinically diseased koalas with a multi-subunit vaccine consisting of Chlamydia pecorum MOMP and NrdB mixed with immune stimulating complex as adjuvant. Following vaccination, there was no increase in inflammatory pathological changes in animals previously infected with Chlamydia. Strong antibody (including neutralizing antibodies) and lymphocyte proliferation responses were recorded in all vaccinated koalas, both healthy and clinically diseased. Vaccine induced antibodies specific for both vaccine antigens were observed not only in plasma but also in ocular secretions. Our data shows that an experimental chlamydial vaccine is safe to use in previously infected koalas, in that it does not worsen infection-associated lesions. Furthermore, the prototype vaccine is effective, as demonstrated by strong levels of neutralizing antibody and lymphocyte proliferation responses in both healthy and clinically diseased koalas. Collectively, this work illustrates the feasibility of developing a safe and effective Chlamydia vaccine as a tool for management of disease in wild koalas.

Source apportionment of ultrafine and fine particle concentrations in Brisbane, Australia

Purpose: To investigate the significance of sources around measurement sites, assist the development of control strategies for the important sources and mitigate the adverse effects of air pollution due to particle size. Methods: In this study, sampling was conducted at two sites located in urban/industrial and residential areas situated at roadsides along the Brisbane Urban Corridor. Ultrafine and fine particle measurements obtained at the two sites in June-July 2002 were analysed by Positive Matrix Factorization (PMF). Results: Six sources were present, including local traffic, two traffic sources, biomass burning, and two currently unidentified sources. Secondary particles had a significant impact at Site 1, while nitrates, peak traffic hours and main roads located close to the source also affected the results for both sites. Conclusions: This significant traffic corridor exemplifies the type of sources present in heavily trafficked locations and future attempts to control pollution in this type of environment could focus on the sources that were identified.

Greek or not : the use of symbols and abbreviations in mathematics

The use of symbols and abbreviations adds uniqueness and complexity to the mathematical language register. In this article, the reader’s attention is drawn to the multitude of symbols and abbreviations which are used in mathematics. The conventions which underpin the use of the symbols and abbreviations and the linguistic difficulties which learners of mathematics may encounter due to the inclusion of the symbolic language are discussed. 2010 NAPLAN numeracy tests are used to illustrate examples of the complexities of the symbolic language of mathematics.

Spot the differences in traditional and social entrepreneurial intention : highlighting the role of human and social capital

There is general agreement in the scientific community that entrepreneurship plays a central role in the growth and development of an economy in rapidly changing environments (Acs & Virgill 2010). In particular, when business activities are regarded as a vehicle for sustainable growth at large, that goes beyond mere economic returns of singular entities, encompassing also social problems and heavily relying on collaborative actions, then we more precisely fall into the domain of ‘social entrepreneurship’(Robinson et al. 2009). In the entrepreneurship literature, prior studies demonstrated the role of intentionality as the best predictor of planned behavior (Ajzen 1991), and assumed that the intention to start a business derives from the perception of desirability and feasibility and from a propensity to act upon an opportunity (Fishbein & Ajzen 1975). Recognizing that starting a business is an intentional act (Krueger et al. 2000) and entrepreneurship is a planned behaviour (Katz & Gartner 1988), models of entrepreneurial intentions have substantial implications for intentionality research in entrepreneurship. The purpose of this paper is to explore the emerging practice of social entrepreneurship by comparing the determinants of entrepreneurial intention in general versus those leading to startups with a social mission. Social entrepreneurial intentions clearly merit to be investigated given that the opportunity identification process is an intentional process not only typical of for profit start-ups, and yet there is a lack of research examining opportunity recognition in social entrepreneurship (Haugh 2005). The key argument is that intentionality in both traditional and social entrepreneurs during the decision-making process of new venture creation is influenced by an individual's perceptions toward opportunities (Fishbein & Ajzen 1975). Besides opportunity recognition, at least two other aspects can substantially influence intentionality: human and social capital (Davidsson, 2003). This paper is set to establish if and to what extent the social intentions of potential entrepreneurs, at the cognitive level, are influenced by opportunities recognition, human capital, and social capital. By applying established theoretical constructs, the paper draws comparisons between ‘for-profit’ and ‘social’ intentionality using two samples of students enrolled in Economy and Business Administration at the University G. d’Annunzio in Pescara, Italy. A questionnaire was submitted to 310 potential entrepreneurs to test the robustness of the model. The collected data were used to measure the theoretical constructs of the paper. Reliability of the multi-item scale for each dimension was measured using Cronbach alpha, and for all the dimensions measures of reliability are above 0.70. We empirically tested the model using structural equation modeling with AMOS. The results allow us to empirically contribute to the argument regarding the influence of human and social cognitive capital on social and non-social entrepreneurial intentions. Moreover, we highlight the importance for further researchers to look deeper into the determinants of traditional and social entrepreneurial intention so that governments can one day define better polices and regulations that promote sustainable businesses with a social imprint, rather than inhibit their formation and growth.

An investigation of gaseous and particulate emissions from compression ignition engines operated with alternative fuels, injection technologies, and combustion strategies

Whilst the compression ignition (CI) engine exhibits many design advantages relative to its spark ignition engine counterpart; such as: high thermal efficiency, fuel economy and low carbon monoxide and hydrocarbon emissions, the issue of Diesel Particulate Matter (DPM) emissions continues to be an unresolved problem for the CI engine. Primarily, this thesis investigates a range of DPM mitigation strategies such as alternative fuels, injection technologies and combustion strategies conducted with a view to determine their impact on the physico-chemical properties of DPM emissions, and consequently to shed light on their likely human health impacts. Regulated gaseous emissions, Nitric oxide (NO), Carbon monoxide (CO), and Hydrocarbons (HCs), were measured in all experimental campaigns, although the major focus in this research program was on particulate emissions...

Understanding the relationships between the calf muscle pump, ankle range of motion and healing for adults with venous leg ulcers: a review of the literature

Exercise offers the potential to improve circulation, wound healing outcomes, and functional and emotional wellbeing for adults experiencing venous leg ulceration. Individuals with chronic leg ulcers typically have multiple comorbidities such as arthritis, asthma, chronic obstructive airways disease, cardiac disease or neuromuscular disorders, which would also benefit from regular exercise. The aim of this review is to highlight the relationships between the calf muscle pump and venous return and range of ankle motion for adults with venous leg ulcers. The effect of exercise will also be considered in relation to the healing rates for adults experiencing venous leg ulceration. The findings suggest there is evidence that exercises which engage the calf muscle pump improve venous return. Ankle range of motion, which is crucial for complete activation of the calf muscle pump, can also be improved with simple, home-based exercise programs. However, observational studies still report that venous leg ulcer patients are less physically active than age-matched controls. Therefore, the behavioural reasons for not exercising must be considered. Only two studies, both underpowered, have assessed the effect of exercise on the healing rates of venous leg ulcers. In conclusion, exercise is feasible with this patient population. However, future studies with larger sample sizes are needed to provide stronger evidence to support the therapeutic benefit of exercise as an adjunct therapy in wound care.

A framework for cost-aware process management : generation of accurate and timely management accounting cost reports

Organisations are constantly seeking efficiency improvements for their business processes in terms of time and cost. Management accounting enables reporting of detailed cost of operations for decision making purpose, although significant effort is required to gather accurate operational data. Business process management is concerned with systematically documenting, managing, automating, and optimising processes. Process mining gives valuable insight into processes through analysis of events recorded by an IT system in the form of an event log with the focus on efficient utilisation of time and resources, although its primary focus is not on cost implications. In this paper, we propose a framework to support management accounting decisions on cost control by automatically incorporating cost data with historical data from event logs for monitoring, predicting and reporting process-related costs. We also illustrate how accurate, relevant and timely management accounting style cost reports can be produced on demand by extending open-source process mining framework ProM.