A two-compartment mechanochemical model of the roles of transforming growth factor-beta and tissue tension in dermal wound healing

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor-beta (TGF-beta) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF-beta and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF-beta in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF-beta significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures.

Monitoring and regulatory role of the balanced scorecard in controlling organisational identities

This thesis employs the theoretical fusion of disciplinary knowledge, interlacing an analysis from both functional and interpretive frameworks and applies these paradigms to three concepts—organisational identity, the balanced scorecard performance measurement system, and control. As an applied thesis, this study highlights how particular public sector organisations are using a range of multi-disciplinary forms of knowledge constructed for their needs to achieve practical outcomes. Practical evidence of this study is not bound by a single disciplinary field or the concerns raised by academics about the rigorous application of academic knowledge. The study’s value lies in its ability to explore how current communication and accounting knowledge is being used for practical purposes in organisational life. The main focus of this thesis is on identities in an organisational communication context. In exploring the theoretical and practical challenges, the research questions for this thesis were formulated as: 1. Is it possible to effectively control identities in organisations by the use of an integrated performance measurement system—the balanced scorecard—and if so, how? 2. What is the relationship between identities and an integrated performance measurement system—the balanced scorecard—in the identity construction process? Identities in the organisational context have been extensively discussed in graphic design, corporate communication and marketing, strategic management, organisational behaviour, and social psychology literatures. Corporate identity is the self-presentation of the personality of an organisation (Van Riel, 1995; Van Riel & Balmer, 1997), and organisational identity is the statement of central characteristics described by members (Albert & Whetten, 2003). In this study, identity management is positioned as a strategically complex task, embracing not only logo and name, but also multiple dimensions, levels and facets of organisational life. Responding to the collaborative efforts of researchers and practitioners in identity conceptualisation and methodological approaches, this dissertation argues that analysis can be achieved through the use of an integrated framework of identity products, patternings and processes (Cornelissen, Haslam, & Balmer, 2007), transforming conceptualisations of corporate identity, organisational identity and identification studies. Likewise, the performance measurement literature from the accounting field now emphasises the importance of ‘soft’ non-financial measures in gauging performance—potentially allowing the monitoring and regulation of ‘collective’ identities (Cornelissen et al., 2007). The balanced scorecard (BSC) (Kaplan & Norton, 1996a), as the selected integrated performance measurement system, quantifies organisational performance under the four perspectives of finance, customer, internal process, and learning and growth. Broadening the traditional performance measurement boundary, the BSC transforms how organisations perceived themselves (Vaivio, 2007). The rhetorical and communicative value of the BSC has also been emphasised in organisational self-understanding (Malina, Nørreklit, & Selto, 2007; Malmi, 2001; Norreklit, 2000, 2003). Thus, this study establishes a theoretical connection between the controlling effects of the BSC and organisational identity construction. Common to both literatures, the aspects of control became the focus of this dissertation, as ‘the exercise or act of achieving a goal’ (Tompkins & Cheney, 1985, p. 180). This study explores not only traditional technical and bureaucratic control (Edwards, 1981), but also concertive control (Tompkins & Cheney, 1985), shifting the locus of control to employees who make their own decisions towards desired organisational premises (Simon, 1976). The controlling effects on collective identities are explored through the lens of the rhetorical frames mobilised through the power of organisational enthymemes (Tompkins & Cheney, 1985) and identification processes (Ashforth, Harrison, & Corley, 2008). In operationalising the concept of control, two guiding questions were developed to support the research questions: 1.1 How does the use of the balanced scorecard monitor identities in public sector organisations? 1.2 How does the use of the balanced scorecard regulate identities in public sector organisations? This study adopts qualitative multiple case studies using ethnographic techniques. Data were gathered from interviews of 41 managers, organisational documents, and participant observation from 2003 to 2008, to inform an understanding of organisational practices and members’ perceptions in the five cases of two public sector organisations in Australia. Drawing on the functional and interpretive paradigms, the effective design and use of the systems, as well as the understanding of shared meanings of identities and identifications are simultaneously recognised. The analytical structure guided by the ‘bracketing’ (Lewis & Grimes, 1999) and ‘interplay’ strategies (Schultz & Hatch, 1996) preserved, connected and contrasted the unique findings from the multi-paradigms. The ‘temporal bracketing’ strategy (Langley, 1999) from the process view supports the comparative exploration of the analysis over the periods under study. The findings suggest that the effective use of the BSC can monitor and regulate identity products, patternings and processes. In monitoring identities, the flexible BSC framework allowed the case study organisations to monitor various aspects of finance, customer, improvement and organisational capability that included identity dimensions. Such inclusion legitimises identity management as organisational performance. In regulating identities, the use of the BSC created a mechanism to form collective identities by articulating various perspectives and causal linkages, and through the cascading and alignment of multiple scorecards. The BSC—directly reflecting organisationally valued premises and legitimised symbols—acted as an identity product of communication, visual symbols and behavioural guidance. The selective promotion of the BSC measures filtered organisational focus to shape unique identity multiplicity and characteristics within the cases. Further, the use of the BSC facilitated the assimilation of multiple identities by controlling the direction and strength of identifications, engaging different groups of members. More specifically, the tight authority of the BSC framework and systems are explained both by technical and bureaucratic controls, while subtle communication of organisational premises and information filtering is achieved through concertive control. This study confirms that these macro top-down controls mediated the sensebreaking and sensegiving process of organisational identification, supporting research by Ashforth, Harrison and Corley (2008). This study pays attention to members’ power of self-regulation, filling minor premises of the derived logic of their organisation through the playing out of organisational enthymemes (Tompkins & Cheney, 1985). Members are then encouraged to make their own decisions towards the organisational premises embedded in the BSC, through the micro bottom-up identification processes including: enacting organisationally valued identities; sensemaking; and the construction of identity narratives aligned with those organisationally valued premises. Within the process, the self-referential effect of communication encouraged members to believe the organisational messages embedded in the BSC in transforming collective and individual identities. Therefore, communication through the use of the BSC continued the self-producing of normative performance mechanisms, established meanings of identities, and enabled members’ self-regulation in identity construction. Further, this research establishes the relationship between identity and the use of the BSC in terms of identity multiplicity and attributes. The BSC framework constrained and enabled case study organisations and members to monitor and regulate identity multiplicity across a number of dimensions, levels and facets. The use of the BSC constantly heightened the identity attributes of distinctiveness, relativity, visibility, fluidity and manageability in identity construction over time. Overall, this research explains the reciprocal controlling relationships of multiple structures in organisations to achieve a goal. It bridges the gap among corporate and organisational identity theories by adopting Cornelissen, Haslam and Balmer’s (2007) integrated identity framework, and reduces the gap in understanding between identity and performance measurement studies. Parallel review of the process of monitoring and regulating identities from both literatures synthesised the theoretical strengths of both to conceptualise and operationalise identities. This study extends the discussion on positioning identity, culture, commitment, and image and reputation measures in integrated performance measurement systems as organisational capital. Further, this study applies understanding of the multiple forms of control (Edwards, 1979; Tompkins & Cheney, 1985), emphasising the power of organisational members in identification processes, using the notion of rhetorical organisational enthymemes. This highlights the value of the collaborative theoretical power of identity, communication and performance measurement frameworks. These case studies provide practical insights about the public sector where existing bureaucracy and desired organisational identity directions are competing within a large organisational setting. Further research on personal identity and simple control in organisations that fully cascade the BSC down to individual members would provide enriched data. The extended application of the conceptual framework to other public and private sector organisations with a longitudinal view will also contribute to further theory building.

Measuring export readiness using a multiple-item index

Since the 1970s the internationalisation process of firms has attracted wide research interest. One of the dominant explanations of firm internationalisation resulting from this research activity is the Uppsala stages model. In this paper, a pre-internationalisation phase is incorporated into the traditional Uppsala model to address the question: What are the antecedents of this model? Four concepts are proposed as the key components that define the experiential learning process underlying a firm’s pre-export phase: export stimuli, attitudinal/psychological commitment, resources and lateral rigidity. Through a survey of 290 Australian exporting and non-exporting small-medium sized firms, data relating to the four pre-internationalisation concepts is collected and an Export Readiness Index (ERI) is constructed through factor analysis. Using logistic regression, the ERI is tested as a tool for analysing export readiness among Australian SMEs.

The role of informal networks in providing effective work opportunities for people with an intellectual disability

Being in paid employment is socially valued, and is linked to health, financial security and time use. Issues arising from a lack of occupational choice and control, and from diminished role partnerships are particularly problematic in the lives of people with an intellectual disability. Informal support networks are shown to influence work opportunities for people without disabilities, but their impact on the work experiences of people with disability has not been thoroughly explored. The experience of 'work' and preparation for work was explored with a group of four people with an intellectual disability (the participants) and the key members of their informal support networks (network members) in New South Wales, Australia. Network members and participants were interviewed and participant observations of work and other activities were undertaken. Data analysis included open, conceptual and thematic coding. Data analysis software assisted in managing the large datasets across multiple team members. The insight and actions of network members created and sustained the employment and support opportunities that effectively matched the needs and interests of the participants. Recommendations for future research are outlined.

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.

An assessment system for evaluation of driving competencies

Automobiles have deeply impacted the way in which we travel but they have also contributed to many deaths and injury due to crashes. A number of reasons for these crashes have been pointed out by researchers. Inexperience has been identified as a contributing factor to road crashes. Driver’s driving abilities also play a vital role in judging the road environment and reacting in-time to avoid any possible collision. Therefore driver’s perceptual and motor skills remain the key factors impacting on road safety. Our failure to understand what is really important for learners, in terms of competent driving, is one of the many challenges for building better training programs. Driver training is one of the interventions aimed at decreasing the number of crashes that involve young drivers. Currently, there is a need to develop comprehensive driver evaluation system that benefits from the advances in Driver Assistance Systems. A multidisciplinary approach is necessary to explain how driving abilities evolves with on-road driving experience. To our knowledge, driver assistance systems have never been comprehensively used in a driver training context to assess the safety aspect of driving. The aim and novelty of this thesis is to develop and evaluate an Intelligent Driver Training System (IDTS) as an automated assessment tool that will help drivers and their trainers to comprehensively view complex driving manoeuvres and potentially provide effective feedback by post processing the data recorded during driving. This system is designed to help driver trainers to accurately evaluate driver performance and has the potential to provide valuable feedback to the drivers. Since driving is dependent on fuzzy inputs from the driver (i.e. approximate distance calculation from the other vehicles, approximate assumption of the other vehicle speed), it is necessary that the evaluation system is based on criteria and rules that handles uncertain and fuzzy characteristics of the driving tasks. Therefore, the proposed IDTS utilizes fuzzy set theory for the assessment of driver performance. The proposed research program focuses on integrating the multi-sensory information acquired from the vehicle, driver and environment to assess driving competencies. After information acquisition, the current research focuses on automated segmentation of the selected manoeuvres from the driving scenario. This leads to the creation of a model that determines a “competency” criterion through the driving performance protocol used by driver trainers (i.e. expert knowledge) to assess drivers. This is achieved by comprehensively evaluating and assessing the data stream acquired from multiple in-vehicle sensors using fuzzy rules and classifying the driving manoeuvres (i.e. overtake, lane change, T-crossing and turn) between low and high competency. The fuzzy rules use parameters such as following distance, gaze depth and scan area, distance with respect to lanes and excessive acceleration or braking during the manoeuvres to assess competency. These rules that identify driving competency were initially designed with the help of expert’s knowledge (i.e. driver trainers). In-order to fine tune these rules and the parameters that define these rules, a driving experiment was conducted to identify the empirical differences between novice and experienced drivers. The results from the driving experiment indicated that significant differences existed between novice and experienced driver, in terms of their gaze pattern and duration, speed, stop time at the T-crossing, lane keeping and the time spent in lanes while performing the selected manoeuvres. These differences were used to refine the fuzzy membership functions and rules that govern the assessments of the driving tasks. Next, this research focused on providing an integrated visual assessment interface to both driver trainers and their trainees. By providing a rich set of interactive graphical interfaces, displaying information about the driving tasks, Intelligent Driver Training System (IDTS) visualisation module has the potential to give empirical feedback to its users. Lastly, the validation of the IDTS system’s assessment was conducted by comparing IDTS objective assessments, for the driving experiment, with the subjective assessments of the driver trainers for particular manoeuvres. Results show that not only IDTS was able to match the subjective assessments made by driver trainers during the driving experiment but also identified some additional driving manoeuvres performed in low competency that were not identified by the driver trainers due to increased mental workload of trainers when assessing multiple variables that constitute driving. The validation of IDTS emphasized the need for an automated assessment tool that can segment the manoeuvres from the driving scenario, further investigate the variables within that manoeuvre to determine the manoeuvre’s competency and provide integrated visualisation regarding the manoeuvre to its users (i.e. trainers and trainees). Through analysis and validation it was shown that IDTS is a useful assistance tool for driver trainers to empirically assess and potentially provide feedback regarding the manoeuvres undertaken by the drivers.

Genome-wide identification and expression analysis of the NF-Y family of transcription factors in Triticum aestivum

Nuclear Factor Y (NF-Y) is a trimeric complex that binds to the CCAAT box, a ubiquitous eukaryotic promoter element. The three subunits NF-YA, NF-YB and NF-YC are represented by single genes in yeast and mammals. However, in model plant species (Arabidopsis and rice) multiple genes encode each subunit providing the impetus for the investigation of the NF-Y transcription factor family in wheat. A total of 37 NF-Y and Dr1 genes (10 NF-YA, 11 NF-YB, 14 NF-YC and 2 Dr1) in Triticum aestivum were identified in the global DNA databases by computational analysis in this study. Each of the wheat NF-Y subunit families could be further divided into 4-5 clades based on their conserved core region sequences. Several conserved motifs outside of the NF-Y core regions were also identified by comparison of NF-Y members from wheat, rice and Arabidopsis. Quantitative RT-PCR analysis revealed that some of the wheat NF-Y genes were expressed ubiquitously, while others were expressed in an organ-specific manner. In particular, each TaNF-Y subunit family had members that were expressed predominantly in the endosperm. The expression of nine NF-Y and two Dr1 genes in wheat leaves appeared to be responsive to drought stress. Three of these genes were up-regulated under drought conditions, indicating that these members of the NF-Y and Dr1 families are potentially involved in plant drought adaptation. The combined expression and phylogenetic analyses revealed that members within the same phylogenetic clade generally shared a similar expression profile. Organ-specific expression and differential response to drought indicate a plant-specific biological role for various members of this transcription factor family.

Myocyte enhancer factor 2C : an osteoblast transcription factor identified by DMSO enhanced mineralization

Rapid mineralization of cultured osteoblasts could be a useful characteristic in stem-cell mediated therapies for fracture and other orthopaedic problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent molecule capable of simulating cell differentiation. We report that, in primary human osteoblasts, DMSO dose-dependently enhanced the expression of osteoblast differentiation markers alkaline phosphatase (ALP) activity and extracellular matrix mineralization. Furthermore, similar DMSO mediated mineralization enhancement was observed in primary osteoblast-like cells differentiated from mouse mesenchymal cells derived from fat, a promising source of starter cells for cell-based therapy. Using a convenient mouse pre-osteoblast model cell line MC3T3-E1 we further investigated this phenomenon showing that numerous osteoblast-expressed genes were elevated in response to DMSO treatment and correlated with enhanced mineralization. Myocyte enhancer factor 2c (Mef2c) was identified as the transcription factor most induced by DMSO, among numerous DMSO-induced genes, suggesting a role for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed expression of Mef2c in osteoblast-like cells in mouse mandible, cortical and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted in defective osteoblast differentiation, decreased ALP activity and matrix mineralization and knockdown of osteoblast specific gene expression, including osteocalcin and bone sialoprotein. Flow on knockdown of bone specific transcription factors, Runx2 and osterix by shRNAi knockdown of Mef2c suggests that Mef2c lies upstream of these two important factors in the cascade of gene expression in osteoblasts.

Multiple analysis of three common genetic alterations associated with thrombophilia

We have previously reported the use of a novel mini-sequencing protocol for detection of the factor V Leiden variant, the first nucleotide change (FNC) technology. This technology is based on a single nucleotide extension of a primer, which is hybridized immediately adjacent to the site of mutation. The extended nucleotide that carries a reporter molecule (fluorescein) has the power to discriminate the genotype at the site of mutation. More recently, the prothrombin 20210 and thermolabile methylene tetrahydrofolate reductase (MTHFR) 677 variants have been identified as possible risk factors associated with thrombophilia. This study describes the use of the FNC technology in a combined assay to detect factor V, prothrombin and MTHFR variants in a population of Australian blood donors, and describes the objective numerical methodology used to determine genotype cut-off values for each genetic variation. Using FNC to test 500 normal blood donors, the incidence of Factor V Leiden was 3.6% (all heterozygous), that of prothrombin 20210 was 2.8% (all heterozygous) and that of MTHFR was 10% (homozygous). The combined FNC technology offers a simple, rapid, automatable DNA-based test for the detection of these three important mutations that are associated with familial thrombophilia. (C) 2000 Lippincott Williams and Wilkins.

Live my work : rural nurses and their multiple perspectives of self

Aim. This paper is a report of a study to explore rural nurses' experiences of mentoring. Background. Mentoring has recently been proposed by governments, advocates and academics as a solution to the problem for retaining rural nurses in the Australian workforce. Action in the form of mentor development workshops has changed the way that some rural nurses now construct supportive relationships as mentoring. Method. A grounded theory design was used with nine rural nurses. Eleven semi-structured interviews were conducted in various states of Australia during 2004-2005. Situational analysis mapping techniques and frame analysis were used in combination with concurrent data generation and analysis and theoretical sampling. Findings. Experienced rural nurses cultivate novices through supportive mentoring relationships. The impetus for such relationships comes from their own histories of living and working in the same community, and this was termed 'live my work'. Rural nurses use multiple perspectives of self in order to manage their interactions with others in their roles as community members, consumers of healthcare services and nurses. Personal strategies adapted to local context constitute the skills that experienced rural nurses pass-on to neophyte rural nurses through mentoring, while at the same time protecting them through troubleshooting and translating local cultural norms. Conclusion. Living and working in the same community creates a set of complex challenges for novice rural nurses that are better faced with a mentor in place. Thus, mentoring has become an integral part of experienced rural nurses' practice to promote staff retention. © 2007 The Authors.

The role of cross-functional teams on the alignment between technology innovation effectiveness and operational effectiveness

Organisations are increasingly investing in complex technological innovations, such as enterprise information systems, with the aim of improving the operation of the business, and in this way gaining competitive advantage. However, the implementation of technological innovations tends to have an excessive focus on either technology innovation effectiveness, or the resulting operational effectiveness. Focusing on either one of them is detrimental to long-term performance. Cross-functional teams have been used by many organisations as a way of involving expertise from different functional areas in the implementation of technologies. The role of boundary spanning actors is discussed as they bring a common language to the cross-functional teams. Multiple regression analysis has been used to identify the structural relationships and provide an explanation for the influence of cross-functional teams, technology innovation effectiveness and operational effectiveness in the continuous improvement of operational performance. The findings indicate that cross functional teams have an indirect influence on continuous improvement of operational performance through the alignment between technology innovation effectiveness and operational effectiveness.

Glycosaminoglycan and growth factor mediated murine calvarial cell proliferation

Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans (GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development. The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems. Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 microg/ml) resulted in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2 (BMP2) and transforming growth factor-beta1 (TGFbeta1) and the isolated cell surface GAGs, differences between the two model systems emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFbeta1 actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGbeta1 effects. These results emphasise the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.

Nursing Sans Frontieres: A Three Year Case Study of Multi-State Registration of Support Nursing Practice Using Information Technology

Objective: To highlight the registration issues for nurses who wish to practice nationally, particularly those practicing within the telehealth sector. Design: As part of a national clinical research study, applications were made to every state and territory for mutual recognition of nursing registration and fee waiver for telenursing cross boarder practice for a period of three years. These processes are described using a case study approach. Outcome: The aim of this case study was to achieve registration in every state and territory of Australia without paying multiple fees by using mutual recognition provisions and the cross-border fee waiver policy of the nurse regulatory authorities in order to practice telenursing. Results: Mutual recognition and fee waiver for cross-border practice was granted unconditionally in two states: Victoria (Vic) and Tasmania (Tas), and one territory: the Northern Territory (NT). The remainder of the Australian states and territories would only grant temporary registration for the period of the project or not at all, due to policy restrictions or nurse regulatory authority (NRA) Board decisions. As a consequence of gaining fee waiver the annual cost of registration was a maximum of $145 per annum as opposed to the potential $959 for initial registration and $625 for annual renewal. Conclusions: Having eight individual nurses Acts and NRAs for a population of 265,000 nurses would clearly indicate a case for over regulation in this country. The structure of regulation of nursing in Australia is a barrier to the changing and evolving role of nurses in the 21st century and a significant factor when considering workforce planning.

The role of idea novelty and relatedness in nascent ventures

The study of venture idea characteristics and the contextual fit between venture ideas and individuals are key research goals in entrepreneurship (Davidsson, 2004). However, to date there has been limited scholarly attention given to these phenomena. Accordingly, this study aims to help fill the gap by investigating the importance of novelty and relatedness of venture ideas in entrepreneurial firms. On the premise that new venture creation is a process and that research should be focused on the early stages of the venturing process, this study primarily focuses its attention on examining how venture idea novelty and relatedness affect the performance in the venture creation process. Different types and degrees of novelty are considered here. Relatedness is shown to be based on individuals’ prior knowledge and resource endowment. Performance in the venture creation process is evaluated according to four possible outcomes: making progress, getting operational, being terminated and achieving positive cash flow. A theoretical model is developed demonstrating the relationship between these variables along with the investment of time and money. Several hypotheses are developed to be tested. Among them, it is hypothesised that novelty hinders short term performance in the venture creation process. On the other hand knowledge and resource relatedness are hypothesised to promote performance. An experimental study was required in order to understand how different types and degrees of novelty and relatedness of venture ideas affect the attractiveness of venture ideas in the eyes of experienced entrepreneurs. Thus, the empirical work in this thesis was based on two separate studies. In the first one, a conjoint analysis experiment was conducted on 32 experienced entrepreneurs in order to ascertain attitudinal preferences regarding venture idea attractiveness based on novelty, relatedness and potential financial gains. This helped to estimate utility values for different levels of different attributes of venture ideas and their relative importance in the attractiveness. The second study was a longitudinal investigation of how venture idea novelty and relatedness affect the performance in the venture creation process. The data for this study is from the Comprehensive Australian Study for Entrepreneurial Emergence (CAUSEE) project that has been established in order to explore the new venture creation process in Australia. CAUSEE collects data from a representative sample of over 30,000 households in Australia using random digit dialling (RDD) telephone interviews. From these cases, data was collected at two points in time during a 12 month period from 493 firms, who are currently involved in the start-up process. Hypotheses were tested and inferences were derived through descriptive statistics, confirmatory factor analysis and structural equation modelling. Results of study 1 indicate that venture idea characteristics have a role in the attractiveness and entrepreneurs prefer to introduce a moderate degree of novelty across all types of venture ideas concerned. Knowledge relatedness is demonstrated to be a more significant factor in attractiveness than resource relatedness. Results of study 2 show that the novelty hinders nascent venture performance. On the other hand, resource relatedness has a positive impact on performance unlike knowledge relatedness which has none. The results of these studies have important implications for potential entrepreneurs, investors, researchers, consultants etc. by developing a better understanding in the venture creation process and its success factors in terms of both theory and practice.

Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.