Urban, regional, national and global knowledge capital [Guest editorial]

Purpose – The purpose of this paper is to introduce the JKM 2010 annual special issue on knowledge based development (KBD) with reference to the multi-level analysis characteristic of the field. ----- ----- Design/methodology/approach – A description of the knowledge management approach at ESOC (European Space Operations Centre of the European Space Agency) is provided first. At the core of this approach is the breakdown of knowledge in individual technical domains followed by coverage analysis and criticality assessment. Such a framework becomes the reference for best knowledge acquisition, transfer and storage locus identification and subsequent knowledge management practices and guidelines. ----- ----- Findings – KBD provides an integrated framework to account for multidisciplinary analyses and multilevel practices in knowledge capital generation, distribution and utilization. ----- ----- Originality/value – The collection of papers included in the annual special issue on KBD provides a representative, composite view of the research topics and applications concerns in the field. Involving a number of disciplines and levels of analysis, issues ranging from the technological gatekeeper to global knowledge flows show the interdependence of KBD concepts and tools.

An advanced implicit meshless approach for fractional partial differential equation in computational mechanics

Recently, the numerical modelling and simulation for fractional partial differential equations (FPDE), which have been found with widely applications in modern engineering and sciences, are attracting increased attentions. The current dominant numerical method for modelling of FPDE is the explicit Finite Difference Method (FDM), which is based on a pre-defined grid leading to inherited issues or shortcomings. This paper aims to develop an implicit meshless approach based on the radial basis functions (RBF) for numerical simulation of time fractional diffusion equations. The discrete system of equations is obtained by using the RBF meshless shape functions and the strong-forms. The stability and convergence of this meshless approach are then discussed and theoretically proven. Several numerical examples with different problem domains are used to validate and investigate accuracy and efficiency of the newly developed meshless formulation. The results obtained by the meshless formations are also compared with those obtained by FDM in terms of their accuracy and efficiency. It is concluded that the present meshless formulation is very effective for the modelling and simulation for FPDE.

Resurrecting the notion of journalistic objectivity : a discussion of journalistic objectivity in one-on-one interviews

A number of recent books on ethics (Hirst and Patching 2005, Tanner et al, 2005, Ward, 2006)have indicated that traditional understandings of journalism "objectivity" are in need of renovation if they are to sustain the claim as a guide to ethical action. Ward argues for the recasting of the notions of traditional objectivity to offer a "pragmatic objectivity" as an alternative and plausible underpinning to ethical journalism practice. He argues that a recast or "pragmatic objectivity" should respond to the changing rhetorical relationship between journalists and their audiences; and, in so doing, should take inspiration from attempts to be objective in other domains---professions such as law and public relations in seeking models. This paper seeks to take a step in that direction through illustrating how journalism interviews do "objectivity" through an adaptation of the principles of the "Fourth Estate" to political interviews. It turns such analysis to the ends of establishing the particular "pragmatic ethic" underpinning such practices and how journalism interviewing techniques has allowed for proactive journalists to strike a workable balance between pursuing the public interest and observing the restraining protocols of modern journalistic practice.

Developments in texture-based vector field visualisation techniques

Vector field visualisation is one of the classic sub-fields of scientific data visualisation. The need for effective visualisation of flow data arises in many scientific domains ranging from medical sciences to aerodynamics. Though there has been much research on the topic, the question of how to communicate flow information effectively in real, practical situations is still largely an unsolved problem. This is particularly true for complex 3D flows. In this presentation we give a brief introduction and background to vector field visualisation and comment on the effectiveness of the most common solutions. We will then give some examples of current development on texture-based techniques, and given practical examples of their use in CFD research and hydrodynamic applications.

The nature of caregiving in children of a parent with multiple sclerosis from multiple sources and the associations between caregiving activities and youth adjustment overtime

This study explored youth caregiving for a parent with multiple sclerosis (MS) from multiple perspectives, and examined associations between caregiving and child negative (behavioural emotional difficulties, somatisation) and positive (life satisfaction, positive affect, prosocial behaviour) adjustment outcomes overtime. A total of 88 families participated; 85 parents with MS, 55 partners and 130 children completed questionnaires at Time 1. Child caregiving was assessed by the Youth Activities of Caregiving Scale (YACS). Child and parent questionnaire data were collected at Time 1 and child data were collected 12 months later (Time 2). Factor analysis of the child and parent YACS data replicated the four factors (instrumental, social-emotional, personal-intimate, domestic-household care), all of which were psychometrically sound. The YACS factors were related to parental illness and caregiving context variables that reflected increased caregiving demands. The Time 1 instrumental and social-emotional care domains were associated with poorer Time 2 adjustment, whereas personal-intimate was related to better adjustment and domestic-household care was unrelated to adjustment. Children and their parents exhibited highest agreement on personal-intimate, instrumental and total caregiving, and least on domestic-household and social-emotional care. Findings delineate the key dimensions of young caregiving in MS and the differential links between caregiving activities and youth adjustment.

A cyclic porphyrin tetramer linked by azo and butadiyne bridges

A soluble cyclic porphyrin oligomer (CPO) consisting of four 5,10- diarylporphyrins linked by alternating azo and butadiyne bridges has been synthesised via an aminated dinickel(II) butadiyne dimer. This is the first cyclic tetramer that combines both azo and butadiyne bridges and extends the azoporphyrin family, which comprises only a very few examples. The electronic absorption spectrum of the tetramer is more similar to spectra of azoporphyrins than to those of butadiyne-linked dimers or tetramer, exhibiting a two component Soret band with a splitting of 4190 cm-1 and a strongly red-shifted Q band maximum at 735 nm.

Personalizing the design of computer-based instruction to enhance learning

This paper reports two studies designed to investigate the effect on learning outcomes of matching individuals' preferred cognitive styles to computer-based instructional (CBI) material. Study 1 considered the styles individually as Verbalizer, Imager, Wholist and Analytic. Study 2 considered the bi-dimensional nature of cognitive styles in order to assess the full ramification of cognitive styles on learning: Analytic/Imager, Analytic/ Verbalizer, Wholist/Imager and the Wholist/Verbalizer. The mix of images and text, the nature of the text material, use of advance organizers and proximity of information to facilitate meaningful connections between various pieces of information were some of the considerations in the design of the CBI material. In a quasi-experimental format, students' cognitive styles were analysed by Cognitive Style Analysis (CSA) software. On the basis of the CSA result, the system defaulted students to either matched or mismatched CBI material by alternating between the two formats. The instructional material had a learning and a test phase. Learning outcome was tested on recall, labelling, explanation and problem-solving tasks. Comparison of the matched and mismatched instruction did not indicate significant difference between the groups, but the consistently better performance by the matched group suggests potential for further investigations where the limitations cited in this paper are eliminated. The result did indicate a significant difference between the four cognitive styles with the Wholist/Verbalizer group performing better then all other cognitive styles. Analysing the difference between cognitive styles on individual test tasks indicated significant difference on recall, labelling and explanation, suggesting that certain test tasks may suit certain cognitive styles.

Clinical indicators of quality for Australian residential aged care facilities : establishing reliability, validity, and quality thresholds

Background: In response to the need for more comprehensive quality assessment within Australian residential aged care facilities, the Clinical Care Indicator (CCI) Tool was developed to collect outcome data as a means of making inferences about quality. A national trial of its effectiveness and a Brisbane-based trial of its use within the quality improvement context determined the CCI Tool represented a potentially valuable addition to the Australian aged care system. This document describes the next phase in the CCI Tool.s development; the aims of which were to establish validity and reliability of the CCI Tool, and to develop quality indicator thresholds (benchmarks) for use in Australia. The CCI Tool is now known as the ResCareQA (Residential Care Quality Assessment). Methods: The study aims were achieved through a combination of quantitative data analysis, and expert panel consultations using modified Delphi process. The expert panel consisted of experienced aged care clinicians, managers, and academics; they were initially consulted to determine face and content validity of the ResCareQA, and later to develop thresholds of quality. To analyse its psychometric properties, ResCareQA forms were completed for all residents (N=498) of nine aged care facilities throughout Queensland. Kappa statistics were used to assess inter-rater and test-retest reliability, and Cronbach.s alpha coefficient calculated to determine internal consistency. For concurrent validity, equivalent items on the ResCareQA and the Resident Classification Scales (RCS) were compared using Spearman.s rank order correlations, while discriminative validity was assessed using known-groups technique, comparing ResCareQA results between groups with differing care needs, as well as between male and female residents. Rank-ordered facility results for each clinical care indicator (CCI) were circulated to the panel; upper and lower thresholds for each CCI were nominated by panel members and refined through a Delphi process. These thresholds indicate excellent care at one extreme and questionable care at the other. Results: Minor modifications were made to the assessment, and it was renamed the ResCareQA. Agreement on its content was reached after two Delphi rounds; the final version contains 24 questions across four domains, enabling generation of 36 CCIs. Both test-retest and inter-rater reliability were sound with median kappa values of 0.74 (test-retest) and 0.91 (inter-rater); internal consistency was not as strong, with a Chronbach.s alpha of 0.46. Because the ResCareQA does not provide a single combined score, comparisons for concurrent validity were made with the RCS on an item by item basis, with most resultant correlations being quite low. Discriminative validity analyses, however, revealed highly significant differences in total number of CCIs between high care and low care groups (t199=10.77, p=0.000), while the differences between male and female residents were not significant (t414=0.56, p=0.58). Clinical outcomes varied both within and between facilities; agreed upper and lower thresholds were finalised after three Delphi rounds. Conclusions: The ResCareQA provides a comprehensive, easily administered means of monitoring quality in residential aged care facilities that can be reliably used on multiple occasions. The relatively modest internal consistency score was likely due to the multi-factorial nature of quality, and the absence of an aggregate result for the assessment. Measurement of concurrent validity proved difficult in the absence of a gold standard, but the sound discriminative validity results suggest that the ResCareQA has acceptable validity and could be confidently used as an indication of care quality within Australian residential aged care facilities. The thresholds, while preliminary due to small sample size, enable users to make judgements about quality within and between facilities. Thus it is recommended the ResCareQA be adopted for wider use.

Implementing low intensity CBT in case management of clients with severe mental illness

In a previous chapter (Dean and Kavanagh, Chapter 37), the authors made a case for applying low intensity (LI) cognitive behaviour therapy (CBT) to people with serious mental illness (SMI). As in other populations, LI CBT interventions typically deal with circumscribed problems or behaviours. LI CBT retains an emphasis on self-management, has restricted content and segment length, and does not necessarily require extensive CBT training. In applying these interventions to SMI, adjustments may be needed to address cognitive and symptomatic difficulties often faced by these groups. What may take a single session in a less affected population may require several sessions or a thematic application of the strategy within case management. In some cases, the LI CBT may begin to appear more like a high-intensity (HI) intervention, albeit simple and with many LI CBT characteristics still retained. So, if goal setting were introduced in one or two sessions, it could clearly be seen as an LI intervention. When applied to several different situations and across many sessions, it may be indistinguishable from a simple HI treatment, even if it retains the same format and is effectively applied by a practitioner with limited CBT training. ----- ----- In some ways, LI CBT should be well suited to case management of patients with SMI. treating staff typically have heavy workloads, and find it difficult to apply time-consuming treatments (Singh et al. 2003). LI CBT may allow provision of support to greater numbers of service users, and allow staff to spend more time on those who need intensive and sustained support. However, the introduction of any change in practice has to address significant challenges, and LI CBT is no exception. ----- ----- Many of the issues that we face in applying LI CBT to routine case management in a mnetal health service and their potential solutions are essentially the same as in a range of other problem domains (Turner and Sanders 2006)- and, indeed, are similar to those in any adoption of innovation (Rogers 2003). Over the last 20 years, several commentators have described barriers to implementing evidence-based innovations in mental health services (Corrigan et al. 1992; Deane et al. 2006; Kavanagh et al. 1993). The aim of the current chapter is to present a cognitive behavioural conceptualisation of problems and potential solutions for dissemination of LI CBT.

Spatiotemporal investigations of DNA damage repair using microbeams

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organisation is still unclear despite its decisive role in determining the fate of the damaged cell. Revealing the dynamic sequence of the repair proteins is therefore critical in understanding how the DNA repair mechanisms work. There are also still open questions regarding the possible movement of damaged chromatin domains and its role as trigger for lesion recognition and signalling in the DNA repair context. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. We have followed the development of radiation-induced foci for three DNA damage markers (i.e. γ-H2AX, 53BP1 and hSSB1) using normal fibroblasts (AG01522), human breast adenocarcinoma cells (MCF7) and human fibrosarcoma cells (HT1080) stably transfected with yellow fluorescent protein fusion proteins following irradiation with the QUB X-ray microbeam (carbon X-rays <2 µm spot). The size and intensity of the foci has been analysed as a function of dose and time post-irradiation to investigate the dynamics of the above-mentioned DNA repair processes and monitor the remodelling of chromatin structure that the cell undergoes to deal with DNA damage.

Validation of the Cannabis Expectancy Questionnaire (CEQ) in adult cannabis users in treatment

Background Outcome expectancies are a key cognitive construct in the etiology, assessment and treatment of Substance Use Disorders. There is a research and clinical need for a cannabis expectancy measure validated in a clinical sample of cannabis users. Method The Cannabis Expectancy Questionnaire (CEQ) was subjected to exploratory (n = 501, mean age 27.45, 78% male) and confirmatory (n = 505, mean age 27.69, 78% male) factor analysis in two separate samples of cannabis users attending an outpatient cannabis treatment program. Weekly cannabis consumption was clinically assessed and patients completed the Severity of Dependence Scale-Cannabis (SDS-C) and the General Health Questionnaire (GHQ-28). Results Two factors representing Negative Cannabis Expectancies and Positive Cannabis Expectancies were identified. These provided a robust statistical and conceptual fit for the data. Internal reliabilities were high. Negative expectancies were associated with greater dependence severity (as measured by the SDS) and positive expectancies with higher consumption. The interaction of positive and negative expectancies was consistently significantly associated with self-reported functioning across all four GHQ-28 scales (Somatic Concerns, Anxiety, Social Dysfunction and Depression). Specifically, within the context of high positive cannabis expectancy, higher negative expectancy was predictive of more impaired functioning. By contrast, within the context of low positive cannabis expectancy, higher negative expectancy was predictive of better functioning. Conclusions The CEQ is the first cannabis expectancy measure to be validated in a sample of cannabis users in treatment. Negative and positive cannabis expectancy domains were uniquely associated with consumption, dependence severity and self-reported mental health functioning.

Conformational flexibility revealed by the crystal structure of a crenarchaeal RadA

Homologous recombinational repair is an essential mechanism for repair of double-strand breaks in DNA. Recombinases of the RecA-fold family play a crucial role in this process, forming filaments that utilize ATP to mediate their interactions with singleand double-stranded DNA. The recombinase molecules present in the archaea (RadA) and eukaryota (Rad51) are more closely related to each other than to their bacterial counterpart (RecA) and, as a result, RadA makes a suitable model for the eukaryotic system. The crystal structure of Sulfolobus solfataricus RadA has been solved to a resolution of 3.2 A° in the absence of nucleotide analogues or DNA, revealing a narrow filamentous assembly with three molecules per helical turn. As observed in other RecA-family recombinases, each RadA molecule in the filament is linked to its neighbour via interactions of a short b-strand with the neighbouring ATPase domain. However, despite apparent flexibility between domains, comparison with other structures indicates conservation of a number of key interactions that introduce rigidity to the system, allowing allosteric control of the filament by interaction with ATP. Additional analysis reveals that the interaction specificity of the five human Rad51 paralogues can be predicted using a simple model based on the RadA structure.

In vitro and in vivo examination of the cell surface glycoprotein CDCP1

A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.

Wellness in higher education : a transformative framework for health related disciplines

The perceived benefits of Wellness Education in University environments are substantiated by a number of studies in relation to the place, impact and purpose of Wellness curricula. Many authors recommend that Wellness curriculum design must include personal experiences, reflective practice and active self-managed learning approaches in order to legitimise the adoption of Wellness as a personal lifestyle approach. Wellness Education provides opportunities to engage in learning self-regulation skills both within and beyond the context of the Wellness construct. Learner success is optimised by creating authentic opportunities to develop and practice self regulation strategies that facilitate making meaning of life's experiences. Such opportunities include provision of options for self determined outcomes and are scaffolded according to learner needs; thus, configuring a learner-centred curriculum in Wellness Education would potentially benefit by overlaying principles from the domains of Self Determination Theory, Self Regulated Learning and Transformative Education Theory to highlight authentic, transformative learning as a lifelong approach to Wellness.

The relative impact of work-related stress, life stress and driving environment stress on driving outcomes

Previous research has shown the association between stress and crash involvement. The impact of stress on road safety may also be mediated by behaviours including cognitive lapses, errors, and intentional traffic violations. This study aimed to provide a further understanding of the impact that stress from different sources may have upon driving behaviour and road safety. It is asserted that both stress extraneous to the driving environment and stress directly elicited by driving must be considered part of a dynamic system that may have a negative impact on driving behaviours. Two hundred and forty-seven public sector employees from Queensland, Australia, completed self-report measures examining demographics, subjective work-related stress, daily hassles, and aspects of general mental health. Additionally, the Driver Behaviour Questionnaire (DBQ) and the Driver Stress Inventory (DSI) were administered. All participants drove for work purposes regularly, however the study did not specifically focus on full-time professional drivers. Confirmatory factor analysis of the predictor variables revealed three factors: DSI negative affect; DSI risk taking; and extraneous influences (daily hassles, work-related stress, and general mental health). Moderate intercorrelations were found between each of these factors confirming the ‘spillover’ effect. That is, driver stress is reciprocally related to stress in other domains including work and domestic life. Structural equation modelling (SEM) showed that the DSI negative affect factor influenced both lapses and errors, whereas the DSI risk-taking factor was the strongest influence on violations. The SEMs also confirmed that daily hassles extraneous to the driving environment may influence DBQ lapses and violations independently. Accordingly, interventions may be developed to increase driver awareness of the dangers of excessive emotional responses to both driving events and daily hassles (e.g. driving fast to ‘blow off steam’ after an argument). They may also train more effective strategies for self-regulation of emotion and coping when encountering stressful situations on the road.