Application of data mining techniques in the prediction of coronary artery disease : use of anaesthesia time-series and patient risk factor data

The high morbidity and mortality associated with atherosclerotic coronary vascular disease (CVD) and its complications are being lessened by the increased knowledge of risk factors, effective preventative measures and proven therapeutic interventions. However, significant CVD morbidity remains and sudden cardiac death continues to be a presenting feature for some subsequently diagnosed with CVD. Coronary vascular disease is also the leading cause of anaesthesia related complications. Stress electrocardiography/exercise testing is predictive of 10 year risk of CVD events and the cardiovascular variables used to score this test are monitored peri-operatively. Similar physiological time-series datasets are being subjected to data mining methods for the prediction of medical diagnoses and outcomes. This study aims to find predictors of CVD using anaesthesia time-series data and patient risk factor data. Several pre-processing and predictive data mining methods are applied to this data. Physiological time-series data related to anaesthetic procedures are subjected to pre-processing methods for removal of outliers, calculation of moving averages as well as data summarisation and data abstraction methods. Feature selection methods of both wrapper and filter types are applied to derived physiological time-series variable sets alone and to the same variables combined with risk factor variables. The ability of these methods to identify subsets of highly correlated but non-redundant variables is assessed. The major dataset is derived from the entire anaesthesia population and subsets of this population are considered to be at increased anaesthesia risk based on their need for more intensive monitoring (invasive haemodynamic monitoring and additional ECG leads). Because of the unbalanced class distribution in the data, majority class under-sampling and Kappa statistic together with misclassification rate and area under the ROC curve (AUC) are used for evaluation of models generated using different prediction algorithms. The performance based on models derived from feature reduced datasets reveal the filter method, Cfs subset evaluation, to be most consistently effective although Consistency derived subsets tended to slightly increased accuracy but markedly increased complexity. The use of misclassification rate (MR) for model performance evaluation is influenced by class distribution. This could be eliminated by consideration of the AUC or Kappa statistic as well by evaluation of subsets with under-sampled majority class. The noise and outlier removal pre-processing methods produced models with MR ranging from 10.69 to 12.62 with the lowest value being for data from which both outliers and noise were removed (MR 10.69). For the raw time-series dataset, MR is 12.34. Feature selection results in reduction in MR to 9.8 to 10.16 with time segmented summary data (dataset F) MR being 9.8 and raw time-series summary data (dataset A) being 9.92. However, for all time-series only based datasets, the complexity is high. For most pre-processing methods, Cfs could identify a subset of correlated and non-redundant variables from the time-series alone datasets but models derived from these subsets are of one leaf only. MR values are consistent with class distribution in the subset folds evaluated in the n-cross validation method. For models based on Cfs selected time-series derived and risk factor (RF) variables, the MR ranges from 8.83 to 10.36 with dataset RF_A (raw time-series data and RF) being 8.85 and dataset RF_F (time segmented time-series variables and RF) being 9.09. The models based on counts of outliers and counts of data points outside normal range (Dataset RF_E) and derived variables based on time series transformed using Symbolic Aggregate Approximation (SAX) with associated time-series pattern cluster membership (Dataset RF_ G) perform the least well with MR of 10.25 and 10.36 respectively. For coronary vascular disease prediction, nearest neighbour (NNge) and the support vector machine based method, SMO, have the highest MR of 10.1 and 10.28 while logistic regression (LR) and the decision tree (DT) method, J48, have MR of 8.85 and 9.0 respectively. DT rules are most comprehensible and clinically relevant. The predictive accuracy increase achieved by addition of risk factor variables to time-series variable based models is significant. The addition of time-series derived variables to models based on risk factor variables alone is associated with a trend to improved performance. Data mining of feature reduced, anaesthesia time-series variables together with risk factor variables can produce compact and moderately accurate models able to predict coronary vascular disease. Decision tree analysis of time-series data combined with risk factor variables yields rules which are more accurate than models based on time-series data alone. The limited additional value provided by electrocardiographic variables when compared to use of risk factors alone is similar to recent suggestions that exercise electrocardiography (exECG) under standardised conditions has limited additional diagnostic value over risk factor analysis and symptom pattern. The effect of the pre-processing used in this study had limited effect when time-series variables and risk factor variables are used as model input. In the absence of risk factor input, the use of time-series variables after outlier removal and time series variables based on physiological variable values’ being outside the accepted normal range is associated with some improvement in model performance.

An identification of factors influencing police workplace motivation

Police work tasks are diverse and require the ability to take command, demonstrate leadership, make serious decisions and be self directed (Beck, 1999; Brunetto & Farr-Wharton, 2002; Howard, Donofrio & Boles, 2002). This work is usually performed in pairs or sometimes by an officer working alone. Operational police work is seldom performed under the watchful eyes of a supervisor and a great amount of reliance is placed on the high levels of motivation and professionalism of individual officers. Research has shown that highly motivated workers produce better outcomes (Whisenand & Rush, 1998; Herzberg, 2003). It is therefore important that Queensland police officers are highly motivated to provide a quality service to the Queensland community. This research aims to identify factors which motivate Queensland police to perform quality work. Researchers acknowledge that there is a lack of research and knowledge in regard to the factors which motivate police (Beck, 1999; Bragg, 1998; Howard, Donofrio & Boles, 2002; McHugh & Verner, 1998). The motivational factors were identified in regard to the demographic variables of; age, sex, rank, tenure and education. The model for this research is Herzberg’s two-factor theory of workplace motivation (1959). Herzberg found that there are two broad types of workplace motivational factors; those driven by a need to prevent loss or harm and those driven by a need to gain personal satisfaction or achievement. His study identified 16 basic sub-factors that operate in the workplace. The research utilised a questionnaire instrument based on the sub-factors identified by Herzberg (1959). The questionnaire format consists of an initial section which sought demographic information about the participant and is followed by 51 Likert scale questions. The instrument is an expanded version of an instrument previously used in doctoral studies to identify sources of police motivation (Holden, 1980; Chiou, 2004). The questionnaire was forwarded to approximately 960 police in the Brisbane, Metropolitan North Region. The data were analysed using Factor Analysis, MANOVAs, ANOVAs and multiple regression analysis to identify the key sources of police motivation and to determine the relationships between demographic variables such as: age, rank, educational level, tenure, generation cohort and motivational factors. A total of 484 officers responded to the questionnaire from the sample population of 960. Factor analysis revealed five broad Prime Motivational Factors that motivate police in their work. The Prime Motivational Factors are: Feeling Valued, Achievement, Workplace Relationships, the Work Itself and Pay and Conditions. The factor Feeling Valued highlighted the importance of positive supportive leaders in motivating officers. Many officers commented that supervisors who only provided negative feedback diminished their sense of feeling valued and were a key source of de-motivation. Officers also frequently commented that they were motivated by operational police work itself whilst demonstrating a strong sense of identity with their team and colleagues. The study showed a general need for acceptance by peers and an idealistic motivation to assist members of the community in need and protect victims of crime. Generational cohorts were not found to exert a significant influence on police motivation. The demographic variable with the single greatest influence on police motivation was tenure. Motivation levels were found to drop dramatically during the first two years of an officer’s service and generally not improve significantly until near retirement age. The findings of this research provide the foundation of a number of recommendations in regard to police retirement, training and work allocation that are aimed to improve police motivation levels. The five Prime Motivational Factor model developed in this study is recommended for use as a planning tool by police leaders to improve motivational and job-satisfaction components of police Service policies. The findings of this study also provide a better understanding of the current sources of police motivation. They are expected to have valuable application for Queensland police human resource management when considering policies and procedures in the areas of motivation, stress reduction and attracting suitable staff to specific areas of responsibility.

Image acquisition and manipulation protocols for CT-PET fusion to improve the accuracy of gross tumour volume localisation for 3D conformal radiotherapy for lung cancer

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.

The Hindraf saga : media and citizenship in Malaysia

In the early part of 2008, a major political upset was pulled off in the Southeast Asian nation of Malaysia when the ruling coalition, Barisan Nasional (National Front), lost its long-held parliamentary majority after the general elections. Given the astonishingly high profile of political bloggers and relatively well established alternative online new sites within the nation, it was not surprising that many new media proponents saw the result as a major triumph of the medium. Through a brief account of the Hindraf (Hindu Rights Action Force) saga and the socio-political dissent nursed, in part, through new media in contemporary Malaysia, this paper seeks to lend context to the events that precede and surround the election as an example of the relationship between media and citizenship in praxis. In so doing it argues that the political turnaround, if indeed it proves to be, cannot be considered the consequence of new media alone. Rather, that to comprehensively assess the implications of new media for citizenship is to take into account the specific histories, conditions and actions (or lack of) of the various social actors involved.

Application of autologous periosteal cells for the regeneration of class III furcation defects in Beagle dogs

The aim of this study was to evaluate the healing of class III furcation defects following transplantation of autogenous periosteal cells combined with b-tricalcium phosphate (b-TCP). Periosteal cells obtained from Beagle dogs’ periosteum explant cultures, were inoculated onto the surface of b-TCP. Class III furcation defects were created in the mandibular premolars. Three experimental groups were used to test the defects’ healing: group A, b-TCP seeded with periosteal cells were transplanted into the defects; group B, b-TCP alone was used for defect filling; and group C, the defect was without filling materials. Twelve weeks post surgery, the tissue samples were collected for histology, immunohistology and X-ray examination. It was found that both the length of newly formed periodontal ligament and the area of newly formed alveolar bone in group A, were significantly increased compared with both group B and C. Furthermore, both the proportion of newly formed periodontal ligament and newly formed alveolar bone in group A were much higher than those of group B and C. The quantity of cementum and its percentage in the defects (group A) were also significantly higher than those of group C. These results indicate that autogenous periosteal cells combined with b-TCP application can improve periodontal tissue regeneration in class III furcation defects.

Alternative analytical methods for the identification of cancer-related symptom clusters

Advances in symptom management strategies through a better understanding of cancer symptom clusters depend on the identification of symptom clusters that are valid and reliable. The purpose of this exploratory research was to investigate alternative analytical approaches to identify symptom clusters for patients with cancer, using readily accessible statistical methods, and to justify which methods of identification may be appropriate for this context. Three studies were undertaken: (1) a systematic review of the literature, to identify analytical methods commonly used for symptom cluster identification for cancer patients; (2) a secondary data analysis to identify symptom clusters and compare alternative methods, as a guide to best practice approaches in cross-sectional studies; and (3) a secondary data analysis to investigate the stability of symptom clusters over time. The systematic literature review identified, in 10 years prior to March 2007, 13 cross-sectional studies implementing multivariate methods to identify cancer related symptom clusters. The methods commonly used to group symptoms were exploratory factor analysis, hierarchical cluster analysis and principal components analysis. Common factor analysis methods were recommended as the best practice cross-sectional methods for cancer symptom cluster identification. A comparison of alternative common factor analysis methods was conducted, in a secondary analysis of a sample of 219 ambulatory cancer patients with mixed diagnoses, assessed within one month of commencing chemotherapy treatment. Principal axis factoring, unweighted least squares and image factor analysis identified five consistent symptom clusters, based on patient self-reported distress ratings of 42 physical symptoms. Extraction of an additional cluster was necessary when using alpha factor analysis to determine clinically relevant symptom clusters. The recommended approaches for symptom cluster identification using nonmultivariate normal data were: principal axis factoring or unweighted least squares for factor extraction, followed by oblique rotation; and use of the scree plot and Minimum Average Partial procedure to determine the number of factors. In contrast to other studies which typically interpret pattern coefficients alone, in these studies symptom clusters were determined on the basis of structure coefficients. This approach was adopted for the stability of the results as structure coefficients are correlations between factors and symptoms unaffected by the correlations between factors. Symptoms could be associated with multiple clusters as a foundation for investigating potential interventions. The stability of these five symptom clusters was investigated in separate common factor analyses, 6 and 12 months after chemotherapy commenced. Five qualitatively consistent symptom clusters were identified over time (Musculoskeletal-discomforts/lethargy, Oral-discomforts, Gastrointestinaldiscomforts, Vasomotor-symptoms, Gastrointestinal-toxicities), but at 12 months two additional clusters were determined (Lethargy and Gastrointestinal/digestive symptoms). Future studies should include physical, psychological, and cognitive symptoms. Further investigation of the identified symptom clusters is required for validation, to examine causality, and potentially to suggest interventions for symptom management. Future studies should use longitudinal analyses to investigate change in symptom clusters, the influence of patient related factors, and the impact on outcomes (e.g., daily functioning) over time.

Examining psychosocial influences on speeding in Australian and Chinese contexts : a social learning approach

Speeding remains a significant contributing factor to road trauma internationally, despite increasingly sophisticated speed management strategies being adopted around the world. Increases in travel speed are associated with increases in crash risk and crash severity. As speed choice is a voluntary behaviour, driver perceptions are important to our understanding of speeding and, importantly, to designing effective behavioural countermeasures. The four studies conducted in this program of research represent a comprehensive approach to examining psychosocial influences on driving speeds in two countries that are at very different levels of road safety development: Australia and China. Akers’ social learning theory (SLT) was selected as the theoretical framework underpinning this research and guided the development of key research hypotheses. This theory was chosen because of its ability to encompass psychological, sociological, and criminological perspectives in understanding behaviour, each of which has relevance to speeding. A mixed-method design was used to explore the personal, social, and legal influences on speeding among car drivers in Queensland (Australia) and Beijing (China). Study 1 was a qualitative exploration, via focus group interviews, of speeding among 67 car drivers recruited from south east Queensland. Participants were assigned to groups based on their age and gender, and additionally, according to whether they self-identified as speeding excessively or rarely. This study aimed to elicit information about how drivers conceptualise speeding as well as the social and legal influences on driving speeds. The findings revealed a wide variety of reasons and circumstances that appear to be used as personal justifications for exceeding speed limits. Driver perceptions of speeding as personally and socially acceptable, as well as safe and necessary were common. Perceptions of an absence of danger associated with faster driving speeds were evident, particularly with respect to driving alone. An important distinction between the speed-based groups related to the attention given to the driving task. Rare speeders expressed strong beliefs about the need to be mindful of safety (self and others) while excessive speeders referred to the driving task as automatic, an absent-minded endeavour, and to speeding as a necessity in order to remain alert and reduce boredom. For many drivers in this study, compliance with speed limits was expressed as discretionary rather than mandatory. Social factors, such as peer and parental influence were widely discussed in Study 1 and perceptions of widespread community acceptance of speeding were noted. In some instances, the perception that ‘everybody speeds’ appeared to act as one rationale for the need to raise speed limits. Self-presentation, or wanting to project a positive image of self was noted, particularly with respect to concealing speeding infringements from others to protect one’s image as a trustworthy and safe driver. The influence of legal factors was also evident. Legal sanctions do not appear to influence all drivers to the same extent. For instance, fear of apprehension appeared to play a role in reducing speeding for many, although previous experiences of detection and legal sanctions seemed to have had limited influence on reducing speeding among some drivers. Disregard for sanctions (e.g., driving while suspended), fraudulent demerit point use, and other strategies to avoid detection and punishment were widely and openly discussed. In Study 2, 833 drivers were recruited from roadside service stations in metropolitan and regional locations in Queensland. A quantitative research strategy assessed the relative contribution of personal, social, and legal factors to recent and future self-reported speeding (i.e., frequency of speeding and intentions to speed in the future). Multivariate analyses examining a range of factors drawn from SLT revealed that factors including self-identity (i.e., identifying as someone who speeds), favourable definitions (attitudes) towards speeding, personal experiences of avoiding detection and punishment for speeding, and perceptions of family and friends as accepting of speeding were all significantly associated with greater self-reported speeding. Study 3 was an exploratory, qualitative investigation of psychosocial factors associated with speeding among 35 Chinese drivers who were recruited from the membership of a motoring organisation and a university in Beijing. Six focus groups were conducted to explore similar issues to those examined in Study 1. The findings of Study 3 revealed many similarities with respect to the themes that arose in Australia. For example, there were similarities regarding personal justifications for speeding, such as the perception that posted limits are unreasonably low, the belief that individual drivers are able to determine safe travel speeds according to personal comfort with driving fast, and the belief that drivers possess adequate skills to control a vehicle at high speed. Strategies to avoid detection and punishment were also noted, though they appeared more widespread in China and also appeared, in some cases, to involve the use of a third party, a topic that was not reported by Australian drivers. Additionally, higher perceived enforcement tolerance thresholds were discussed by Chinese participants. Overall, the findings indicated perceptions of a high degree of community acceptance of speeding and a perceived lack of risk associated with speeds that were well above posted speed limits. Study 4 extended the exploratory research phase in China with a quantitative investigation involving 299 car drivers recruited from car washes in Beijing. Results revealed a relatively inexperienced sample with less than 5 years driving experience, on average. One third of participants perceived that the certainty of penalties when apprehended was low and a similar proportion of Chinese participants reported having previously avoided legal penalties when apprehended for speeding. Approximately half of the sample reported that legal penalties for speeding were ‘minimally to not at all’ severe. Multivariate analyses revealed that past experiences of avoiding detection and punishment for speeding, as well as favourable attitudes towards speeding, and perceptions of strong community acceptance of speeding were most strongly associated with greater self-reported speeding in the Chinese sample. Overall, the results of this research make several important theoretical contributions to the road safety literature. Akers’ social learning theory was found to be robust across cultural contexts with respect to speeding; similar amounts of variance were explained in self-reported speeding in the quantitative studies conducted in Australia and China. Historically, SLT was devised as a theory of deviance and posits that deviance and conformity are learned in the same way, with the balance of influence stemming from the ways in which behaviour is rewarded and punished (Akers, 1998). This perspective suggests that those who speed and those who do not are influenced by the same mechanisms. The inclusion of drivers from both ends of the ‘speeding spectrum’ in Study 1 provided an opportunity to examine the wider utility of SLT across the full range of the behaviour. One may question the use of a theory of deviance to investigate speeding, a behaviour that could, arguably, be described as socially acceptable and prevalent. However, SLT seemed particularly relevant to investigating speeding because of its inclusion of association, imitation, and reinforcement variables which reflect the breadth of factors already found to be potentially influential on driving speeds. In addition, driving is a learned behaviour requiring observation, guidance, and practice. Thus, the reinforcement and imitation concepts are particularly relevant to this behaviour. Finally, current speed management practices are largely enforcement-based and rely on the principles of behavioural reinforcement captured within the reinforcement component of SLT. Thus, the application of SLT to a behaviour such as speeding offers promise in advancing our understanding of the factors that influence speeding, as well as extending our knowledge of the application of SLT. Moreover, SLT could act as a valuable theoretical framework with which to examine other illegal driving behaviours that may not necessarily be seen as deviant by the community (e.g., mobile phone use while driving). This research also made unique contributions to advancing our understanding of the key components and the overall structure of Akers’ social learning theory. The broader SLT literature is lacking in terms of a thorough structural understanding of the component parts of the theory. For instance, debate exists regarding the relevance of, and necessity for including broader social influences in the model as captured by differential association. In the current research, two alternative SLT models were specified and tested in order to better understand the nature and extent of the influence of differential association on behaviour. Importantly, the results indicated that differential association was able to make a unique contribution to explaining self-reported speeding, thereby negating the call to exclude it from the model. The results also demonstrated that imitation was a discrete theoretical concept that should also be retained in the model. The results suggest a need to further explore and specify mechanisms of social influence in the SLT model. In addition, a novel approach was used to operationalise SLT variables by including concepts drawn from contemporary social psychological and deterrence-based research to enhance and extend the way that SLT variables have traditionally been examined. Differential reinforcement was conceptualised according to behavioural reinforcement principles (i.e., positive and negative reinforcement and punishment) and incorporated concepts of affective beliefs, anticipated regret, and deterrence-related concepts. Although implicit in descriptions of SLT, little research has, to date, made use of the broad range of reinforcement principles to understand the factors that encourage or inhibit behaviour. This approach has particular significance to road user behaviours in general because of the deterrence-based nature of many road safety countermeasures. The concept of self-identity was also included in the model and was found to be consistent with the definitions component of SLT. A final theoretical contribution was the specification and testing of a full measurement model prior to model testing using structural equation modelling. This process is recommended in order to reduce measurement error by providing an examination of the psychometric properties of the data prior to full model testing. Despite calls for such work for a number of decades, the current work appears to be the only example of a full measurement model of SLT. There were also a number of important practical implications that emerged from this program of research. Firstly, perceptions regarding speed enforcement tolerance thresholds were highlighted as a salient influence on driving speeds in both countries. The issue of enforcement tolerance levels generated considerable discussion among drivers in both countries, with Australian drivers reporting lower perceived tolerance levels than Chinese drivers. It was clear that many drivers used the concept of an enforcement tolerance in determining their driving speed, primarily with the desire to drive faster than the posted speed limit, yet remaining within a speed range that would preclude apprehension by police. The quantitative results from Studies 2 and 4 added support to these qualitative findings. Together, the findings supported previous research and suggested that a travel speed may not be seen as illegal until that speed reaches a level over the prescribed enforcement tolerance threshold. In other words, the enforcement tolerance appears to act as a ‘de facto’ speed limit, replacing the posted limit in the minds of some drivers. The findings from the two studies conducted in China (Studies 2 and 4) further highlighted the link between perceived enforcement tolerances and a ‘de facto’ speed limit. Drivers openly discussed driving at speeds that were well above posted speed limits and some participants noted their preference for driving at speeds close to ‘50% above’ the posted limit. This preference appeared to be shaped by the perception that the same penalty would be imposed if apprehended, irrespective of what speed they travelling (at least up to 50% above the limit). Further research is required to determine whether the perceptions of Chinese drivers are mainly influenced by the Law of the People’s Republic of China or by operational practices. Together, the findings from both studies in China indicate that there may be scope to refine enforcement tolerance levels, as has happened in other jurisdictions internationally over time, in order to reduce speeding. Any attempts to do so would likely be assisted by the provision of information about the legitimacy and purpose of speed limits as well as risk factors associated with speeding because these issues were raised by Chinese participants in the qualitative research phase. Another important practical implication of this research for speed management in China is the way in which penalties are determined. Chinese drivers described perceptions of unfairness and a lack of transparency in the enforcement system because they were unsure of the penalty that they would receive if apprehended. Steps to enhance the perceived certainty and consistency of the system to promote a more equitable approach to detection and punishment would appear to be welcomed by the general driving public and would be more consistent with the intended theoretical (deterrence) basis that underpins the current speed enforcement approach. The use of mandatory, fixed penalties may assist in this regard. In many countries, speeding attracts penalties that are dependent on the severity of the offence. In China, there may be safety benefits gained from the introduction of a similar graduated scale of speeding penalties and fixed penalties might also help to address the issue of uncertainty about penalties and related perceptions of unfairness. Such advancements would be in keeping with the principles of best practice for speed management as identified by the World Health Organisation. Another practical implication relating to legal penalties, and applicable to both cultural contexts, relates to the issues of detection and punishment avoidance. These two concepts appeared to strongly influence speeding in the current samples. In Australia, detection avoidance strategies reported by participants generally involved activities that are not illegal (e.g., site learning and remaining watchful for police vehicles). The results from China were similar, although a greater range of strategies were reported. The most common strategy reported in both countries for avoiding detection when speeding was site learning, or familiarisation with speed camera locations. However, a range of illegal practices were also described by Chinese drivers (e.g., tampering with or removing vehicle registration plates so as to render the vehicle unidentifiable on camera and use of in-vehicle radar detectors). With regard to avoiding punishment when apprehended, a range of strategies were reported by drivers from both countries, although a greater range of strategies were reported by Chinese drivers. As the results of the current research indicated that detection avoidance was strongly associated with greater self-reported speeding in both samples, efforts to reduce avoidance opportunities are strongly recommended. The practice of randomly scheduling speed camera locations, as is current practice in Queensland, offers one way to minimise site learning. The findings of this research indicated that this practice should continue. However, they also indicated that additional strategies are needed to reduce opportunities to evade detection. The use of point-to-point speed detection (also known as sectio

Modelling and execution of asset management process via workflow automation

An Asset Management (AM) life-cycle constitutes a set of processes that align with the development, operation and maintenance of assets, in order to meet the desired requirements and objectives of the stake holders of the business. The scope of AM is often broad within an organization due to the interactions between its internal elements such as human resources, finance, technology, engineering operation, information technology and management, as well as external elements such as governance and environment. Due to the complexity of the AM processes, it has been proposed that in order to optimize asset management activities, process modelling initiatives should be adopted. Although organisations adopt AM principles and carry out AM initiatives, most do not document or model their AM processes, let alone enacting their processes (semi-) automatically using a computer-supported system. There is currently a lack of knowledge describing how to model AM processes through a methodical and suitable manner so that the processes are streamlines and optimized and are ready for deployment in a computerised way. This research aims to overcome this deficiency by developing an approach that will aid organisations in constructing AM process models quickly and systematically whilst using the most appropriate techniques, such as workflow technology. Currently, there is a wealth of information within the individual domains of AM and workflow. Both fields are gaining significant popularity in many industries thus fuelling the need for research in exploring the possible benefits of their cross-disciplinary applications. This research is thus inspired to investigate these two domains to exploit the application of workflow to modelling and execution of AM processes. Specifically, it will investigate appropriate methodologies in applying workflow techniques to AM frameworks. One of the benefits of applying workflow models to AM processes is to adapt and enable both ad-hoc and evolutionary changes over time. In addition, this can automate an AM process as well as to support the coordination and collaboration of people that are involved in carrying out the process. A workflow management system (WFMS) can be used to support the design and enactment (i.e. execution) of processes and cope with changes that occur to the process during the enactment. So far few literatures can be found in documenting a systematic approach to modelling the characteristics of AM processes. In order to obtain a workflow model for AM processes commonalities and differences between different AM processes need to be identified. This is the fundamental step in developing a conscientious workflow model for AM processes. Therefore, the first stage of this research focuses on identifying the characteristics of AM processes, especially AM decision making processes. The second stage is to review a number of contemporary workflow techniques and choose a suitable technique for application to AM decision making processes. The third stage is to develop an intermediate ameliorated AM decision process definition that improves the current process description and is ready for modelling using the workflow language selected in the previous stage. All these lead to the fourth stage where a workflow model for an AM decision making process is developed. The process model is then deployed (semi-) automatically in a state-of-the-art WFMS demonstrating the benefits of applying workflow technology to the domain of AM. Given that the information in the AM decision making process is captured at an abstract level within the scope of this work, the deployed process model can be used as an executable guideline for carrying out an AM decision process in practice. Moreover, it can be used as a vanilla system that, once being incorporated with rich information from a specific AM decision making process (e.g. in the case of a building construction or a power plant maintenance), is able to support the automation of such a process in a more elaborated way.

Towards improved speech recognition for resource poor languages

In recent times, the improved levels of accuracy obtained by Automatic Speech Recognition (ASR) technology has made it viable for use in a number of commercial products. Unfortunately, these types of applications are limited to only a few of the world’s languages, primarily because ASR development is reliant on the availability of large amounts of language specific resources. This motivates the need for techniques which reduce this language-specific, resource dependency. Ideally, these approaches should generalise across languages, thereby providing scope for rapid creation of ASR capabilities for resource poor languages. Cross Lingual ASR emerges as a means for addressing this need. Underpinning this approach is the observation that sound production is largely influenced by the physiological construction of the vocal tract, and accordingly, is human, and not language specific. As a result, a common inventory of sounds exists across languages; a property which is exploitable, as sounds from a resource poor, target language can be recognised using models trained on resource rich, source languages. One of the initial impediments to the commercial uptake of ASR technology was its fragility in more challenging environments, such as conversational telephone speech. Subsequent improvements in these environments has gained consumer confidence. Pragmatically, if cross lingual techniques are to considered a viable alternative when resources are limited, they need to perform under the same types of conditions. Accordingly, this thesis evaluates cross lingual techniques using two speech environments; clean read speech and conversational telephone speech. Languages used in evaluations are German, Mandarin, Japanese and Spanish. Results highlight that previously proposed approaches provide respectable results for simpler environments such as read speech, but degrade significantly when in the more taxing conversational environment. Two separate approaches for addressing this degradation are proposed. The first is based on deriving better target language lexical representation, in terms of the source language model set. The second, and ultimately more successful approach, focuses on improving the classification accuracy of context-dependent (CD) models, by catering for the adverse influence of languages specific phonotactic properties. Whilst the primary research goal in this thesis is directed towards improving cross lingual techniques, the catalyst for investigating its use was based on expressed interest from several organisations for an Indonesian ASR capability. In Indonesia alone, there are over 200 million speakers of some Malay variant, provides further impetus and commercial justification for speech related research on this language. Unfortunately, at the beginning of the candidature, limited research had been conducted on the Indonesian language in the field of speech science, and virtually no resources existed. This thesis details the investigative and development work dedicated towards obtaining an ASR system with a 10000 word recognition vocabulary for the Indonesian language.

Max Dupain and the photography of Australian architecture

This thesis considers Max Dupain (1911-1992) and his contribution to the development of architectural photography in Australia. Through his continuous and prolific output over six decades of professional photography Dupain greatly stimulated awareness of and interest in Australian architecture. Before Dupain began specialising in the field, little consistent professional architectural photography had been practised in Australia. He and some of his close associates subsequently developed architectural photography as both a specialised branch of photography and - perhaps more significantly - as a necessary adjunct to architectural practice. In achieving these dual accomplishments, Dupain and like-minded practitioners succeeded in elevating architectural photography to the status of a discipline in its own right. They also gave Australians generally a deeper understanding of the heritage represented by the nation's built environment. At the same time, some of the photographic images he created became firmly fixed in the public imagination as historical icons within the development of a distinctive Australian tradition in the visual arts. Within his chosen field Dupain was the dominant Australian figure of his time. He was instrumental in breaking the link with Pictorialism by bringing Modernist and Documentary perspectives to Australian architectural photography. He was an innovator in the earlier decades of his professional career, however, his photographic techniques and practice did not develop beyond that. By the end of the 1980s he had largely lost touch with the technology and techniques of contemporary practice. Dupain's reputation, which has continued growing since his death in 1992, therefore arises from reasons other than his photographic images alone. It reflects his accomplishment in raising his fellow citizens' awareness of a worthwhile home-grown artistic tradition.

Visual arts, technology and education : how can teaching and learning in high school visual arts classrooms be enriched by the use of computer technology?

Whilst a variety of studies has appeared over the last decade addressing the gap between the potential promised by computers and the reality experienced in the classroom by teachers and students, few have specifically addressed the situation as it pertains to the visual arts classroom. The aim of this study was to explore the reality of the classroom use of computers for three visual arts highschool teachers and determine how computer technology might enrich visual arts teaching and learning. An action research approach was employed to enable the researcher to understand the situation from the teachers' points of view while contributing to their professional practice. The wider social context surrounding this study is characterised by an increase in visual communications brought about by rapid advances in computer technology. The powerful combination of visual imagery and computer technology is illustrated by continuing developments in the print, film and television industries. In particular, the recent growth of interactive multimedia epitomises this combination and is significant to this study as it represents a new form of publishing of great interest to educators and artists alike. In this social context, visual arts education has a significant role to play. By cultivating a critical awareness of the implications of technology use and promoting a creative approach to the application of computer technology within the visual arts, visual arts education is in a position to provide an essential service to students who will leave high school to participate in a visual information age as both consumers and producers.

An ecology of centre-based child care

The studies in the thesis were derived from a program of research focused on centre-based child care in Australia. The studies constituted an ecological analysis as they examined proximal and distal factors which have the potential to affect children's developmental opportunities (Bronfenbrenner, 1979). The project was conducted in thirty-two child care centres located in south-east Queensland. Participants in the research included staff members at the centres, families using the centres and their children. The first study described the personal and professional characteristics of one hundred and forty-four child care workers, as well as their job satisfaction and job commitment. Factors impinging on the stability of care afforded to children were examined, specifically child care workers' intentions to leave their current position and actual staff turnover at a twelve month follow-up. This is an ecosystem analysis (Bronfenbrenner & Crouter, 1983), as it examined the world of work for carers; a setting not directly involving the developing child, but which has implications for children's experiences. Staff job satisfaction was focused on working with children and other adults, including parents and colleagues. Involvement with children was reported as being the most rewarding aspect of the work. This intrinsic satisfaction was enough to sustain caregivers' efforts to maintain their employment in child care programs. It was found that, while improving working conditions may help to reduce turnover, it is likely that moderate turnover rates will remain as child care staff work in relatively small centres and they leave in order to improve career prospects. Departure from a child care job appeared to be as much about improving career opportunities or changing personal circumstances, as it was about poor wages and working conditions. In the second study, factors that influence maternal satisfaction with child care arrangements were examined. The focus included examination of the nature and qualities of parental interaction with staff. This was a mesosystem analysis (Bronfenbrenner & Crouter, 1983), as it considered the links between family and child care settings. Two hundred and twenty-two questionnaires were returned from mothers whose children were enrolled in the participating centres. It was found that maternal satisfaction with child care encompassed the domains of child-centred and parent-centred satisfaction. The nature and range of responses in the quantitative and qualitative data indicated that these parents were genuinely satisfied with their children's care. In the prediction of maternal satisfaction with child care, single parents, mothers with high role satisfaction, and mothers who were satisfied with the frequency of staff contact and degree of supportive communication had higher levels of satisfaction with their child care arrangements. The third study described the structural and process variations within child care programs and examined program differences for compliance with regulations and differences by profit status of the centre, as a microsystem analysis (Bronfenbrenner, 1979). Observations were made in eighty-three programs which served children from two to five years. The results of the study affirmed beliefs that nonprofit centres are superior in the quality of care provided, although this was not to a level which meant that the care in for-profit centres was inadequate. Regulation of structural features of child care programs, per se, did not guarantee higher quality child care as measured by global or process indicators. The final study represented an integration of a range of influences in child care and family settings which may impact on development. Features of child care programs which predict children's social and cognitive development, while taking into account child and family characteristics, were identified. Results were consistent with other research findings which show that child and family characteristics and child care quality predict children's development. Child care quality was more important to the prediction of social development, while family factors appeared to be more predictive of cognitive/language development. An influential variable predictive of development was the period of time which the child had been in the centre. This highlighted the importance of the stability of child care arrangements. Child care quality features which had most influence were global ratings of the qualities of the program environment. However, results need to be interpreted cautiously as the explained variance in the predictive models developed was low. The results of these studies are discussed in terms of the implications for practice and future research. Considerations for an expanded view of ecological approaches to child care research are outlined. Issues discussed include the need to generate child care research which is relevant to social policy development, the implications of market driven policies for child care services, professionalism and professionalisation of child care work, and the need to reconceptualise child care research when the goal is to develop greater theoretical understanding about child care environments and developmental processes.

A life jacket with holes- : a case study of 'temporary engagement' : a strategy used by Education Queensland to employ beginning secondary teachers

This research investigated the impact of Education Queensland's employment policy and practices for beginning secondary teachers appointed on temporary engagement. The context was the public secondary school sector within the state of Queensland, Australia. The study was set within a context of the changing nature of work from full-time permanent employment towards casual, fixed-term contracts, temporary and part-time employment, a trend reflected in the employment patterns for teachers within Australia. Two broad categories of literature relating to the research problem of this thesis were reviewed, namely the beginning teacher and permanency or tenure. The focus in the research literature on beginning teachers was the professional experiences of teachers within the classroom and school. There was a paucity of research that considered the working and industrial conditions of temporary employment for beginning teachers or the personal and professional implications of this form of employment. The review of the context and literature was conceptualised as a Beginning Temporary Teacher Theoretical Framework which served to inform the study. Using a qualitative case study methodology, the research techniques employed for the thesis were semi-structured interview and document analysis. A simultaneously conducted research project in which the researcher participated entitled 'Winning the Lottery? Beginning Teachers on Temporary Engagement' foregrounded this thesis in terms of refining the research question, contributing to the literature and in the selection of the participants. For this case study the perspectives of four distinct yet inter-related categories of professionals were sought. These included four beginning secondary teachers, three school administrators, a Senior Personnel Officer with Education Queensland, and a representative from the Queensland Teachers' Union. The research findings indicated that none of the beginning teachers or other professionals viewed starting a career in teaching on temporary engagement as the ideal. The negative features identified were the differential treatment received and the high level of uncertainty associated with temporary employment. Differential treatment tended to indicate 'less' entitlements, in terms of access to induction and professional development, recreational and sick leave, acceptance by and expectations of other colleagues, and avenues of redress in grievance cases. Moreover, interviews indicated a high level of uncertainty in terms of starting within the teaching profession, commencing at a new school, and a regular income. In addition, frequent changes in schools and/or cohorts of students exacerbated levels of uncertainty. The beginning teachers reported significantly decreased motivation, self-esteem and sense of belonging, and increased stress levels. There was an even more marked negative impact on those beginning teachers who had experienced a higher number of temporary engagements and schools in their first year of teaching. Conversely, strong staff support and a reasonable length of time in the one school improved the quality of the beginning teachers' experiences. The overall impact of being on temporary engagement resulted in delayed permanent position appointments, decreased commitment to particular schools and to Education Queensland as the employing authority, and for two of the beginning teachers, it produced a desire to seek alternative employment. The implementation of Education Queensland's policies relating to working conditions and entitlements for these temporary beginning teachers at the school level was revealed to be less than satisfactory. There was a tendency towards 'just-in- time' management of the beginning teacher on temporary engagement. The beginning teachers received 'less-than-messages' about access to and use of departmental documentation, support through induction and professional development, and their transition from temporary to permanent employment. To ensure a more systematic, supportive and inclusive process for managing the temporary beginning teacher, a conceptual framework entitled 'Continuums of Tension' was developed. The four continuums included permanent employment - temporary employment; system perspective - individual perspective; teaching as a profession - teaching as a job; and the permanent beginning teacher - university graduate. The general principles of the human resource policies of Education Queensland were based on a commitment to permanent employment, a system's perspective, viewing teaching as a profession and a homogeneous group of permanent beginning teachers. Contrasting with this, the beginning teacher on temporary engagement tended to operate from the position of temporary employment and a perspective that was individually based. Their priorities therefore included the 'occupational' aspects of being a temporary teacher striving to become permanent. Thus there existed a tension or contradiction between the general principles of human resource policies within Education Queensland and the employment experiences of beginning teachers on temporary engagement. The study proposed three actions for resolution to address the aforementioned tensions. The actions included: (a) the effective provision and targeted communication of information; (b) support, induction and professional development; and (c) a coordinated approach between Education Queensland, Queensland Teachers' Union, the Universities and the beginning teacher. These actions are fm1her refined to include: (a) an induction kit to suppm1 the individual through the pre-employment to permanent employee phases, (b) an extrapolation of the roles and responsibilities of Education Queensland personnel charged with supporting the beginning temporary teacher, and (c) a series of recommendations to effect a coordinated approach amongst the key stakeholders. The theoretical and conceptual frameworks have provided a means of addressing the identified needs of the beginning teacher on temporary engagement. As such, this study has contributed to the research literature on teacher employment and professionalism and aims to provide a beginning temporary teacher with managed professional and occupational support.

The expression of ADAM-9 and -10 in prostate cancer and their regulation by dihydrotestosterone, insulin-like growth Factor-1 and epidermal growth factor

Prostrate Cancer(PCa)is the most common cause of cancer death amongst Western males. PCa occurs in two distinct stages. In its early stage, growth and development is dependent primarily on male sex hormones (androgens) such as testosterone, although other growth factors have roles maintaining PCa cell survival in this stage. In the later stage of PCa development, growth and.maintenance is independent of androgen stimulation and growth factors including Insulin-like Growth Factor -1 (IGf.:·l) and Epidermal Growth Factor (EGF) are thought to have more crucial roles in cell survival and PCa progression. PCa, in its late stages, is highly aggressive and metastatic, that is, tumorigenic cells migrate from the primary site of the body (prostate) and travel via the systemic and lymphatic circulation, residing and colonising in the bone, lymph node, lung, and in more rare cases, the brain. Metastasis involves both cell migration and tissue degradation activities. The degradation of the extracellular matrix (ECM), the tissue surrounding the organ, is mediated in part by members of a family of 26 proteins called the Matrix Metalloproteases (MMPs), whilst ceil adhesion molecules, of which proteins known as Integrins are included, mediate ce11 migration. A family of proteins known as the ADAMs (A Disintegrin . And Metalloprotease domain) were a recently characterised family at the commencement of this study and now comprise 34 members. Because of their dual nature, possessing an active metaiioprotease domain, homologous to that of the MMPs, and an integrin-binding domain capable of regulating cell-cell and cell-ECM contacts, it was thought likely that members of the ADAMs family may have implications for the progression of aggressive cancers such as those ofthe prostate. This study focussed on two particular ADAMs -9 and -10. ADAM-9 has an active metalloprotease domain, which has been shown to degrade constituents of the ECM, including fibronectin, in vitro. It also has an integrin-binding capacity through association with key integrins involved in PCa progression, such as a6~1. ADAM-10 has no such integrin binding activities, but its bovine orthologue, MADM, is able to degrade coHagen type IV, a major component of basement membranes. It is likely human ADAM-10 has the same activity. It is also known to cleave Ll -a protein involved in cell anchorage activities - and collagen type XVII - which is a principal component of the hemidesmosomes of cellular tight junctions. The cleavage of these proteins enables the cell to be released from the surrounding environment and commence migratory activities, as required in metastasis. Previous studies in this laboratory showed the mRNA expression of the five ADAMs -9,- 10, -11, -15 and -17 in PCa cell lines, characteristic of androgen-dependent and androgen independent disease. These studies were furthered by the characterisation of AD AM-9, -10 and -17 mRNA regulation by Dihydrotestosterone (DHT) in the androgen-responsive cell line (LNCaP). ADAM-9 and -10 mRNA levels were elevated in response to DHT stimulation. Further to these observations, the expression of ADAM-9 and -10 was shown in primary prostate biopsies from patients with PCa. ADAM-1 0 was expressed in the cytoplasm and on the ceH membrane in epithelial and basal cells ofbenign prostate glands, but in high-grade PCa glands, ADAM-I 0 expression was localised to the nucleus and its expression levels appeared to be elevated when compared to low-grade PCa glands. These studies provided a strong background for the hypothesis that ADAM-9 and -10 have key roles in the development ofPCa and provided a basis for further studies.The aims of this study were to: 1) characterise the expression, localisation and levels, of ADAM-9 and -10 mRNA and protein in cell models representing characteristics of normal through androgen-dependent to androgen-independent PCa, as well as to expand the primary PCa biopsy data for ADAM-9 and ADAM-10 to encompass PCa bone metastases 2) establish an in vitro cell system, which could express elevated levels of ADAM-1 0 so that functional cell-based assays such as cell migration, invasion and attachment could be carried out, and 3) to extend the previous hormonal regulation data, to fully characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in the hormonal/growth factor responsive cell line LNCaP. For aim 1 (expression of ADAM-9 and -10 mRNA and protein), ADAM-9 and -10 mRNA were characterised by R T -PCR, while their protein products were analysed by Western blot. Both ADAM-9 and -10 mRNA and protein were expressed at readily detectable levels across progressively metastatic PCa cell lines model that represent characteristics of low-grade,. androgen-dependent (LNCaP and C4) to high-grade, androgen-independent (C4-2 and C4-2B) PCa. When the non-tumorigenic prostate cell line RWPE-1 was compared with the metastatic PCa cell line PC-3, differential expression patterns were seen by Western blot analysis. For ADAM-9, the active form was expressed at higher levels in RWPE-1, whilst subcellular fractionation showed that the active form of ADAM-9 was predominantly located in the cell nucleus. For ADAM-I 0, in both of the cell Jines, a nuclear specific isoform of the mature, catalytically active ADAM-I 0 was found. This isoforrn differed by -2 kDa in Mr (smaller) than the cytoplasmic specific isoform. Unprocessed ADAM-I 0 was readily detected in R WPE-1 cell lines but only occasionally detected in PC-3 cell lines. Immunocytochemistry using ADAM-9 and -10 specific antibodies confirmed nuclear, cytoplasmic and membrane expression of both ADAMs in these two cell lines. To examine the possibility of ADAM-9 and -10 being shed into the extracellular environment, membrane vesicles that are constitutively shed from the cell surface and contain membrane-associated proteins were collected from the media of the prostate cell lines RWPE-1, LNCaP and PC-3. ADAM-9 was readily detectable in RWPE- 1 and LNCaP cell membrane vesicles by Western blot analysis, but not in PC-3 cells, whilst the expression of ADAM-I 0 was detected in shed vesicles from each of these prostate cell lines. By Laser Capture Microdissection (LCM), secretory epithelial cells of primary prostate gland biopsies were isolated from benign and malignant glands. These secretory cells, by Western blot analysis, expressed similar Mr bands for ADAM-9 and -10 that were found in PCa cell lines in vitro, indicating that the nuclear specific isoforrn of ADAM-I 0 was present in PCa primary tumours and may represent the predominantly nuclear form of ADAM-I 0 expression, previously shown in high-grade PCa by immunohistochemistry (IHC). ADAM-9 and -10 were also examined by IHC in bone metastases taken from PCa patients at biopsy. Both ADAMs could be detected at levels similar to those shown for Prostate Specific Antigen (PSA) in these biopsies. Furthermore, both ADAM-9 and -10 were predominantly membrane- bound with occasional nuclear expression. For aim 2, to establish a cell system that over-expressed levels of ADAM-10, two fulllength ADAM-I 0 mammalian expression vectors were constructed; ADAM-I 0 was cloned into pcDNA3.1, which contains a CMV promoter, and into pMEP4, containing an inducible metallothionine promoter, whose activity is stimulated by the addition of CdC}z. The efficiency of these two constructs was tested by way of transient transfection in the PCa cell line PC-3, whilst the pcDNA3.1 construct was also tested in the RWPE-1 prostate cell line. Resultant Western blot analysis for all transient transfection assays showed that levels of ADAM-I 0 were not significantly elevated in any case, when compared to levels of the housekeeping gene ~-Tubulin, despite testing various levels of vector DNA, and, for pMEP4, the induction of the transfected cell system with different degrees of stimulation with CdCh to activate the metallothionine promoter post-transfection. Another study in this laboratory found similar results when the same full length ADAM-10 sequence was cloned into a Green Fluorescent Protein (GFP) expressing vector, as no fluorescence was observed by means of transient tran sfection in the same, and other, PCa cell lines. It was hypothesised that the Kozak sequence included in the full-length construct (human ADAMI 0 naturally occurring sequence) is not strong enough to initiate translation in an artificial system, in cells, which, as described in Aim 1, are already expressing readily detectable levels of endogenous ADAM-10. As a result, time constraints prevented any further progress with Aim 2 and functional studies including cell attachment, invasion and migration were unable to be explored. For Aim 3, to characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in LNCaP cells, the levels of ADAM-9 and -10 mRNA were not stimulated by DHT or IGF-I alone, despite our previous observations that initially characterised ADAM-9 and -10 mRNA as being responsive to DHT. However, IGF-1 in synergy with DHT did significantly elevate mRNA levels ofboth ADAMs. In the case of ADAM-9 and -10 protein, the same trends of stimulation as found at the rnRNA level were shown by Western blot analysis when ADAM-9 and -10 signal intensity was normalised with the housekeeping protein ~-Tubulin. For EGF treatment, both ADAM-9 and -10 mRNA and protein levels were significantly elevated, and further investigation vm found this to be the case for each of these ADAMs proteins in the nuclear fractions of LNCaP cells. These studies are the first to describe extensively, the expression and hormonal/growth factor regulation of two members of the ADAMs family ( -9 and -1 0) in PCa. These observations imply that the expression of ADAM-9 and -10 have varied roles in PCa whilst it develops from androgen-sensitive (early stage disease), through to an androgeninsensitive (late-stage), metastatic disease. Further studies are now required to investigate the several key areas of focus that this research has revealed, including: • Investigation of the cellular mechanisms that are involved in actively transporting the ADAMs to the cell's nuclear compartment and the ADAMs functional roles in the cell nucleus. • The construction of a full-length human ADAM-10 mammalian expression construct with the introduction of a new Kozak sequence, that elevates ADAM-I 0 expression in an in vitro cell system are required, so that functional assays such as cell invasion, migration and attachment may be carried out to fmd the functional consequences of ADAM expression on cellular behaviour. • The regulation studies also need to be extended by confirming the preliminary observations that the nuclear levels of ADAMs may also be elevated by hormones and growth factors such as DHT, IGF-1 and EGF, as well as the regulation of levels of plasma membrany vesicle associated ADAM expression. Given the data presented in this study, it is likely the ADAMs have differential roles throughout the development of PCa due to their differential cellular localisation and synergistic growth-factor regulation. These observations, along with those further studies outlined above, are necessary in identifying these specific components ofPCa metastasis to which the ADAMs may contribute.

Monte Carlo modelling of X-ray absorptiometry and its application to body composition studies

This thesis applies Monte Carlo techniques to the study of X-ray absorptiometric methods of bone mineral measurement. These studies seek to obtain information that can be used in efforts to improve the accuracy of the bone mineral measurements. A Monte Carlo computer code for X-ray photon transport at diagnostic energies has been developed from first principles. This development was undertaken as there was no readily available code which included electron binding energy corrections for incoherent scattering and one of the objectives of the project was to study the effects of inclusion of these corrections in Monte Carlo models. The code includes the main Monte Carlo program plus utilities for dealing with input data. A number of geometrical subroutines which can be used to construct complex geometries have also been written. The accuracy of the Monte Carlo code has been evaluated against the predictions of theory and the results of experiments. The results show a high correlation with theoretical predictions. In comparisons of model results with those of direct experimental measurements, agreement to within the model and experimental variances is obtained. The code is an accurate and valid modelling tool. A study of the significance of inclusion of electron binding energy corrections for incoherent scatter in the Monte Carlo code has been made. The results show this significance to be very dependent upon the type of application. The most significant effect is a reduction of low angle scatter flux for high atomic number scatterers. To effectively apply the Monte Carlo code to the study of bone mineral density measurement by photon absorptiometry the results must be considered in the context of a theoretical framework for the extraction of energy dependent information from planar X-ray beams. Such a theoretical framework is developed and the two-dimensional nature of tissue decomposition based on attenuation measurements alone is explained. This theoretical framework forms the basis for analytical models of bone mineral measurement by dual energy X-ray photon absorptiometry techniques. Monte Carlo models of dual energy X-ray absorptiometry (DEXA) have been established. These models have been used to study the contribution of scattered radiation to the measurements. It has been demonstrated that the measurement geometry has a significant effect upon the scatter contribution to the detected signal. For the geometry of the models studied in this work the scatter has no significant effect upon the results of the measurements. The model has also been used to study a proposed technique which involves dual energy X-ray transmission measurements plus a linear measurement of the distance along the ray path. This is designated as the DPA( +) technique. The addition of the linear measurement enables the tissue decomposition to be extended to three components. Bone mineral, fat and lean soft tissue are the components considered here. The results of the model demonstrate that the measurement of bone mineral using this technique is stable over a wide range of soft tissue compositions and hence would indicate the potential to overcome a major problem of the two component DEXA technique. However, the results also show that the accuracy of the DPA( +) technique is highly dependent upon the composition of the non-mineral components of bone and has poorer precision (approximately twice the coefficient of variation) than the standard DEXA measurements. These factors may limit the usefulness of the technique. These studies illustrate the value of Monte Carlo computer modelling of quantitative X-ray measurement techniques. The Monte Carlo models of bone densitometry measurement have:- 1. demonstrated the significant effects of the measurement geometry upon the contribution of scattered radiation to the measurements, 2. demonstrated that the statistical precision of the proposed DPA( +) three tissue component technique is poorer than that of the standard DEXA two tissue component technique, 3. demonstrated that the proposed DPA(+) technique has difficulty providing accurate simultaneous measurement of body composition in terms of a three component model of fat, lean soft tissue and bone mineral,4. and provided a knowledge base for input to decisions about development (or otherwise) of a physical prototype DPA( +) imaging system. The Monte Carlo computer code, data, utilities and associated models represent a set of significant, accurate and valid modelling tools for quantitative studies of physical problems in the fields of diagnostic radiology and radiography.