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

A comparison of the psychological, social, and legal factors contributing to speeding and drink driving behaviour

Within Australia, motor vehicle injury is the leading cause of hospital admissions and fatalities. Road crash data reveals that among the factors contributing to crashes in Queensland, speed and alcohol continue to be overrepresented. While alcohol is the number one contributing factor to fatal crashes, speeding also contributes to a high proportion of crashes. Research indicates that risky driving is an important contributor to road crashes. However, it has been debated whether all risky driving behaviours are similar enough to be explained by the same combination of factors. Further, road safety authorities have traditionally relied upon deterrence based countermeasures to reduce the incidence of illegal driving behaviours such as speeding and drink driving. However, more recent research has focussed on social factors to explain illegal driving behaviours. The purpose of this research was to examine and compare the psychological, legal, and social factors contributing to two illegal driving behaviours: exceeding the posted speed limit and driving when over the legal blood alcohol concentration (BAC) for the drivers licence type. Complementary theoretical perspectives were chosen to comprehensively examine these two behaviours including Akers’ social learning theory, Stafford and Warr’s expanded deterrence theory, and personality perspectives encompassing alcohol misuse, sensation seeking, and Type-A behaviour pattern. The program of research consisted of two phases: a preliminary pilot study, and the main quantitative phase. The preliminary pilot study was undertaken to inform the development of the quantitative study and to ensure the clarity of the theoretical constructs operationalised in this research. Semi-structured interviews were conducted with 11 Queensland drivers recruited from Queensland Transport Licensing Centres and Queensland University of Technology (QUT). These interviews demonstrated that the majority of participants had engaged in at least one of the behaviours, or knew of someone who had. It was also found among these drivers that the social environment in which both behaviours operated, including family and friends, and the social rewards and punishments associated with the behaviours, are important in their decision making. The main quantitative phase of the research involved a cross-sectional survey of 547 Queensland licensed drivers. The aim of this study was to determine the relationship between speeding and drink driving and whether there were any similarities or differences in the factors that contribute to a driver’s decision to engage in one or the other. A comparison of the participants self-reported speeding and self-reported drink driving behaviour demonstrated that there was a weak positive association between these two behaviours. Further, participants reported engaging in more frequent speeding at both low (i.e., up to 10 kilometres per hour) and high (i.e., 10 kilometres per hour or more) levels, than engaging in drink driving behaviour. It was noted that those who indicated they drove when they may be over the legal limit for their licence type, more frequently exceeded the posted speed limit by 10 kilometres per hour or more than those who complied with the regulatory limits for drink driving. A series of regression analyses were conducted to investigate the factors that predict self-reported speeding, self-reported drink driving, and the preparedness to engage in both behaviours. In relation to self-reported speeding (n = 465), it was found that among the sociodemographic and person-related factors, younger drivers and those who score high on measures of sensation seeking were more likely to report exceeding the posted speed limit. In addition, among the legal and psychosocial factors it was observed that direct exposure to punishment (i.e., being detected by police), direct punishment avoidance (i.e., engaging in an illegal driving behaviour and not being detected by police), personal definitions (i.e., personal orientation or attitudes toward the behaviour), both the normative and behavioural dimensions of differential association (i.e., refers to both the orientation or attitude of their friends and family, as well as the behaviour of these individuals), and anticipated punishments were significant predictors of self-reported speeding. It was interesting to note that associating with significant others who held unfavourable definitions towards speeding (the normative dimension of differential association) and anticipating punishments from others were both significant predictors of a reduction in self-reported speeding. In relation to self-reported drink driving (n = 462), a logistic regression analysis indicated that there were a number of significant predictors which increased the likelihood of whether participants had driven in the last six months when they thought they may have been over the legal alcohol limit. These included: experiences of direct punishment avoidance; having a family member convicted of drink driving; higher levels of Type-A behaviour pattern; greater alcohol misuse (as measured by the AUDIT); and the normative dimension of differential association (i.e., associating with others who held favourable attitudes to drink driving). A final logistic regression analysis examined the predictors of whether the participants reported engaging in both drink driving and speeding versus those who reported engaging in only speeding (the more common of the two behaviours) (n = 465). It was found that experiences of punishment avoidance for speeding decreased the likelihood of engaging in both speeding and drink driving; whereas in the case of drink driving, direct punishment avoidance increased the likelihood of engaging in both behaviours. It was also noted that holding favourable personal definitions toward speeding and drink driving, as well as higher levels of on Type-A behaviour pattern, and greater alcohol misuse significantly increased the likelihood of engaging in both speeding and drink driving. This research has demonstrated that the compliance with the regulatory limits was much higher for drink driving than it was for speeding. It is acknowledged that while speed limits are a fundamental component of speed management practices in Australia, the countermeasures applied to both speeding and drink driving do not appear to elicit the same level of compliance across the driving population. Further, the findings suggest that while the principles underpinning the current regime of deterrence based countermeasures are sound, current enforcement practices are insufficient to force compliance among the driving population, particularly in the case of speeding. Future research should further examine the degree of overlap between speeding and drink driving behaviour and whether punishment avoidance experiences for a specific illegal driving behaviour serve to undermine the deterrent effect of countermeasures aimed at reducing the incidence of another illegal driving behaviour. Furthermore, future work should seek to understand the factors which predict engaging in speeding and drink driving behaviours at the same time. Speeding has shown itself to be a pervasive and persistent behaviour, hence it would be useful to examine why road safety authorities have been successful in convincing the majority of drivers of the dangers of drink driving, but not those associated with speeding. In conclusion, the challenge for road safety practitioners will be to convince drivers that speeding and drink driving are equally risky behaviours, with the ultimate goal to reduce the prevalence of both behaviours.

The experiences of learner drivers, provisional drivers and supervisors with graduated driver licensing in two Australian jurisdictions

Newly licensed drivers on a provisional or intermediate licence have the highest crash risk when compared with any other group of drivers. In comparison, learner drivers have the lowest crash risk. Graduated driver licensing is one countermeasure that has been demonstrated to effectively reduce the crashes of novice drivers. This thesis examined the graduated driver licensing systems in two Australian states in order to better understand the behaviour of learner drivers, provisional drivers and the supervisors of learner drivers. By doing this, the thesis investigated the personal, social and environmental influences on novice driver behaviour as well as providing effective baseline data against which to measure subsequent changes to the licensing systems. In the first study, conducted prior to the changes to the graduated driver licensing system introduced in mid-2007, drivers who had recently obtained their provisional licence in Queensland and New South Wales were interviewed by telephone regarding their experiences while driving on their learner licence. Of the 687 eligible people approached to participate at driver licensing centres, 392 completed the study representing a response rate of 57.1 per cent. At the time the data was collected, New South Wales represented a more extensive graduated driver licensing system when compared with Queensland. The results suggested that requiring learners to complete a mandated number of hours of supervised practice impacts on the amount of hours that learners report completing. While most learners from New South Wales reported meeting the requirement to complete 50 hours of practice, it appears that many stopped practising soon after this goal was achieved. In contrast, learners from Queensland, who were not required to complete a specific number of hours at the time of the survey, tended to fall into three groups. The first group appeared to complete the minimum number of hours required to pass the test (less than 26 hours), the second group completed 26 to 50 hours of supervised practice while the third group completed significantly more practice than the first two groups (over 100 hours of supervised practice). Learner drivers in both states reported generally complying with the road laws and were unlikely to report that they had been caught breaking the road rules. They also indicated that they planned to obey the road laws once they obtained their provisional licence. However, they were less likely to intend to comply with recommended actions to reduce crash risk such as limiting their driving at night. This study also identified that there were relatively low levels of unaccompanied driving (approximately 15 per cent of the sample), very few driving offences committed (five per cent of the sample) and that learner drivers tended to use a mix of private and professional supervisors (although the majority of practice is undertaken with private supervisors). Consistent with the international literature, this study identified that very few learner drivers had experienced a crash (six per cent) while on their learner licence. The second study was also conducted prior to changes to the graduated driver licensing system and involved follow up interviews with the participants of the first study after they had approximately 21 months driving experience on their provisional licence. Of the 392 participants that completed the first study, 233 participants completed the second interview (representing a response rate of 59.4 per cent). As with the first study, at the time the data was collected, New South Wales had a more extensive graduated driver licensing system than Queensland. For instance, novice drivers from New South Wales were required to progress through two provisional licence phases (P1 and P2) while there was only one provisional licence phase in Queensland. Among the participants in this second study, almost all provisional drivers (97.9 per cent) owned or had access to a vehicle for regular driving. They reported that they were unlikely to break road rules, such as driving after a couple of drinks, but were also unlikely to comply with recommended actions, such as limiting their driving at night. When their provisional driving behaviour was compared to the stated intentions from the first study, the results suggested that their intentions were not a strong predictor of their subsequent behaviour. Their perception of risk associated with driving declined from when they first obtained their learner licence to when they had acquired provisional driving experience. Just over 25 per cent of participants in study two reported that they had been caught committing driving offences while on their provisional licence. Nearly one-third of participants had crashed while driving on a provisional licence, although few of these crashes resulted in injuries or hospitalisations. To complement the first two studies, the third study examined the experiences of supervisors of learner drivers, as well as their perceptions of their learner’s experiences. This study was undertaken after the introduction of the new graduated driver licensing systems in Queensland and New South Wales in mid- 2007, providing insights into the impacts of these changes from the perspective of supervisors. The third study involved an internet survey of 552 supervisors of learner drivers. Within the sample, approximately 50 per cent of participants supervised their own child. Other supervisors of the learner drivers included other parents or stepparents, professional driving instructors and siblings. For two-thirds of the sample, this was the first learner driver that they had supervised. Participants had provided an average of 54.82 hours (sd = 67.19) of supervision. Seventy-three per cent of participants indicated that their learners’ logbooks were accurate or very accurate in most cases, although parents were more likely than non-parents to report that their learners’ logbook was accurate (F (1,546) = 7.74, p = .006). There was no difference between parents and non-parents regarding whether they believed the log book system was effective (F (1,546) = .01, p = .913). The majority of the sample reported that their learner driver had had some professional driving lessons. Notwithstanding this, a significant proportion (72.5 per cent) believed that parents should be either very involved or involved in teaching their child to drive, with parents being more likely than non-parents to hold this belief. In the post mid-2007 graduated driver licensing system, Queensland learner drivers are able to record three hours of supervised practice in their log book for every hour that is completed with a professional driving instructor, up to a total of ten hours. Despite this, there was no difference identified between Queensland and New South Wales participants regarding the amount of time that they reported their learners spent with professional driving instructors (X2(1) = 2.56, p = .110). Supervisors from New South Wales were more likely to ensure that their learner driver complied with the road laws. Additionally, with the exception of drug driving laws, New South Wales supervisors believed it was more important to teach safety-related behaviours such as remaining within the speed limit, car control and hazard perception than those from Queensland. This may be indicative of more intensive road safety educational efforts in New South Wales or the longer time that graduated driver licensing has operated in that jurisdiction. However, other factors may have contributed to these findings and further research is required to explore the issue. In addition, supervisors reported that their learner driver was involved in very few crashes (3.4 per cent) and offences (2.7 per cent). This relatively low reported crash rate is similar to that identified in the first study. Most of the graduated driver licensing research to date has been applied in nature and lacked a strong theoretical foundation. These studies used Akers’ social learning theory to explore the self-reported behaviour of novice drivers and their supervisors. This theory was selected as it has previously been found to provide a relatively comprehensive framework for explaining a range of driver behaviours including novice driver behaviour. Sensation seeking was also used in the first two studies to complement the non-social rewards component of Akers’ social learning theory. This program of research identified that both Akers’ social learning theory and sensation seeking were useful in predicting the behaviour of learner and provisional drivers over and above socio-demographic factors. Within the first study, Akers’ social learning theory accounted for an additional 22 per cent of the variance in learner driver compliance with the law, over and above a range of socio-demographic factors such as age, gender and income. The two constructs within Akers’ theory which were significant predictors of learner driver compliance were the behavioural dimension of differential association relating to friends, and anticipated rewards. Sensation seeking predicted an additional six per cent of the variance in learner driver compliance with the law. When considering a learner driver’s intention to comply with the law while driving on a provisional licence, Akers’ social learning theory accounted for an additional 10 per cent of the variance above socio-demographic factors with anticipated rewards being a significant predictor. Sensation seeking predicted an additional four per cent of the variance. The results suggest that the more rewards individuals anticipate for complying with the law, the more likely they are to obey the road rules. Further research is needed to identify which specific rewards are most likely to encourage novice drivers’ compliance with the law. In the second study, Akers’ social learning theory predicted an additional 40 per cent of the variance in self-reported compliance with road rules over and above socio-demographic factors while sensation seeking accounted for an additional five per cent of the variance. A number of Aker’s social learning theory constructs significantly predicted provisional driver compliance with the law, including the behavioural dimension of differential association for friends, the normative dimension of differential association, personal attitudes and anticipated punishments. The consistent prediction of additional variance by sensation seeking over and above the variables within Akers’ social learning theory in both studies one and two suggests that sensation seeking is not fully captured within the non social rewards dimension of Akers’ social learning theory, at least for novice drivers. It appears that novice drivers are strongly influenced by the desire to engage in new and intense experiences. While socio-demographic factors and the perception of risk associated with driving had an important role in predicting the behaviour of the supervisors of learner drivers, Akers’ social learning theory provided further levels of prediction over and above these factors. The Akers’ social learning theory variables predicted an additional 14 per cent of the variance in the extent to which supervisors ensured that their learners complied with the law and an additional eight per cent of the variance in the supervisors’ provision of a range of practice experiences. The normative dimension of differential association, personal attitudes towards the use of professional driving instructors and anticipated rewards were significant predictors for supervisors ensuring that their learner complied with the road laws, while the normative dimension was important for range of practice. This suggests that supervisors who engage with other supervisors who ensure their learner complies with the road laws and provide a range of practice to their own learners are more likely to also engage in these behaviours. Within this program of research, there were several limitations including the method of recruitment of participants within the first study, the lower participation rate in the second study, an inability to calculate a response rate for study three and the use of self-report data for all three studies. Within the first study, participants were only recruited from larger driver licensing centres to ensure that there was a sufficient throughput of drivers to approach. This may have biased the results due to the possible differences in learners that obtain their licences in locations with smaller licensing centres. Only 59.4 per cent of the sample in the first study completed the second study. This may be a limitation if there was a common reason why those not participating were unable to complete the interview leading to a systematic impact on the results. The third study used a combination of a convenience and snowball sampling which meant that it was not possible to calculate a response rate. All three studies used self-report data which, in many cases, is considered a limitation. However, self-report data may be the only method that can be used to obtain some information. This program of research has a number of implications for countermeasures in both the learner licence phase and the provisional licence phase. During the learner phase, licensing authorities need to carefully consider the number of hours that they mandate learner drivers must complete before they obtain their provisional driving licence. If they mandate an insufficient number of hours, there may be inadvertent negative effects as a result of setting too low a limit. This research suggests that logbooks may be a useful tool for learners and their supervisors in recording and structuring their supervised practice. However, it would appear that the usage rates for logbooks will remain low if they remain voluntary. One strategy for achieving larger amounts of supervised practice is for learner drivers and their supervisors to make supervised practice part of their everyday activities. As well as assisting the learner driver to accumulate the required number of hours of supervised practice, it would ensure that they gain experience in the types of environments that they will probably encounter when driving unaccompanied in the future, such as to and from education or work commitments. There is also a need for policy processes to ensure that parents and professional driving instructors communicate effectively regarding the learner driver’s progress. This is required as most learners spend at least some time with a professional instructor despite receiving significant amounts of practice with a private supervisor. However, many supervisors did not discuss their learner’s progress with the driving instructor. During the provisional phase, there is a need to strengthen countermeasures to address the high crash risk of these drivers. Although many of these crashes are minor, most involve at least one other vehicle. Therefore, there are social and economic benefits to reducing these crashes. If the new, post-2007 graduated driver licensing systems do not significantly reduce crash risk, there may be a need to introduce further provisional licence restrictions such as separate night driving and peer passenger restrictions (as opposed to the hybrid version of these two restrictions operating in both Queensland and New South Wales). Provisional drivers appear to be more likely to obey some provisional licence laws, such as lower blood alcohol content limits, than others such as speed limits. Therefore, there may be a need to introduce countermeasures to encourage provisional drivers to comply with specific restrictions. When combined, these studies provided significant information regarding graduated driver licensing programs. This program of research has investigated graduated driver licensing utilising a cross-sectional and longitudinal design in order to develop our understanding of the experiences of novice drivers that progress through the system in order to help reduce crash risk once novice drivers commence driving by themselves.

A comprehensive investigation of the risky driving behaviour of young novice drivers

Young novice drivers - that is, drivers aged 16-25 years who are relatively inexperienced in driving on the road and have a novice (Learner, Provisional) driver's licence - have been overrepresented in car crash, injury and fatality statistics around the world for decades. There are numerous persistent characteristics evident in young novice driver crashes, fatalities and offences, including variables relating to the young driver themselves, broader social influences which include their passengers, the car they drive, and when and how they drive, and their risky driving behaviour in particular. Moreover, there are a range of psychosocial factors influencing the behaviour of young novice drivers, including the social influences of parents and peers, and person-related factors such as age-related factors, attitudes, and sensation seeking. Historically, a range of approaches have been developed to manage the risky driving behaviour of young novice drivers. Traditional measures predominantly relying upon education have had limited success in regulating the risky driving behaviour of the young novice driver. In contrast, interventions such as graduated driver licensing (GDL) which acknowledges young novice drivers' limitations - principally pertaining to their chronological and developmental age, and their driving inexperience - have shown to be effective in ameliorating this pervasive public health problem. In practice, GDL is a risk management tool that is designed to reduce driving at risky times (e.g., at night) or in risky driving conditions (e.g., with passengers), while still enabling novice drivers to obtain experience. In this regard, the GDL program in Queensland, Australia, was considerably enhanced in July 2007, and major additions to the program include mandated Learner practice of 100 hours recorded in a logbook, and passenger limits during night driving in the Provisional phase. Road safety researchers have also continued to consider the influential role played by the young driver's psychosocial characteristics, including psychological traits and states. In addition, whilst the majority of road safety user research is epidemiological in nature, contemporary road safety research is increasingly applying psychological and criminological theories. Importantly, such theories not only can guide young novice driver research, they can also inform the development and evaluation of countermeasures targeting their risky driving behaviour. The research is thus designed to explore the self-reported behaviours - and the personal, psychosocial, and structural influences upon the behaviours - of young novice drivers This thesis incorporates three stages of predominantly quantitative research to undertake a comprehensive investigation of the risky driving behaviour of young novices. Risky driving behaviour increases the likelihood of the young novice driver being involved in a crash which may harm themselves or other road users, and deliberate risky driving such as driving in excess of the posted speed limits is the focus of the program of research. The extant literature examining the nature of the risky behaviour of the young novice driver - and the contributing factors for this behaviour - while comprehensive, has not led to the development of a reliable instrument designed specifically to measure the risky behaviour of the young novice driver. Therefore the development and application of such a tool (the Behaviour of Young Novice Drivers Scale, or BYNDS) was foremost in the program of research. In addition to describing the driving behaviours of the young novice, a central theme of this program of research was identifying, describing, and quantifying personal, behavioural, and environmental influences upon young novice driver risky behaviour. Accordingly the 11 papers developed from the three stages of research which comprise this thesis are framed within Bandura's reciprocal determinism model which explicitly considers the reciprocal relationship between the environment, the person, and their behaviour. Stage One comprised the foundation research and operationalised quantitative and qualitative methodologies to finalise the instrument used in Stages Two and Three. The first part of Stage One involved an online survey which was completed by 761 young novice drivers who attended tertiary education institutions across Queensland. A reliable instrument for measuring the risky driving behaviour of young novices was developed (the BYNDS) and is currently being operationalised in young novice driver research in progress at the Centre for Injury Research and Prevention in Philadelphia, USA. In addition, regression analyses revealed that psychological distress influenced risky driving behaviour, and the differential influence of depression, anxiety, sensitivity to punishments and rewards, and sensation seeking propensity were explored. Path model analyses revealed that punishment sensitivity was mediated by anxiety and depression; and the influence of depression, anxiety, reward sensitivity and sensation seeking propensity were moderated by the gender of the driver. Specifically, for males, sensation seeking propensity, depression, and reward sensitivity were predictive of self-reported risky driving, whilst for females anxiety was also influential. In the second part of Stage One, 21 young novice drivers participated in individual and small group interviews. The normative influences of parents, peers, and the Police were explicated. Content analysis supported four themes of influence through punishments, rewards, and the behaviours and attitudes of parents and friends. The Police were also influential upon the risky driving behaviour of young novices. The findings of both parts of Stage One informed the research of Stage Two. Stage Two was a comprehensive investigation of the pre-Licence and Learner experiences, attitudes, and behaviours, of young novice drivers. In this stage, 1170 young novice drivers from across Queensland completed an online or paper survey exploring their experiences, behaviours and attitudes as a pre- and Learner driver. The majority of novices did not drive before they were licensed (pre-Licence driving) or as an unsupervised Learner, submitted accurate logbooks, intended to follow the road rules as a Provisional driver, and reported practicing predominantly at the end of the Learner period. The experience of Learners in the enhanced-GDL program were also examined and compared to those of Learner drivers who progressed through the former-GDL program (data collected previously by Bates, Watson, & King, 2009a). Importantly, current-GDL Learners reported significantly more driving practice and a longer Learner period, less difficulty obtaining practice, and less offence detection and crash involvement than Learners in the former-GDL program. The findings of Stage Two informed the research of Stage Three. Stage Three was a comprehensive exploration of the driving experiences, attitudes and behaviours of young novice drivers during their first six months of Provisional 1 licensure. In this stage, 390 of the 1170 young novice drivers from Stage Two completed another survey, and data collected during Stages Two and Three allowed a longitudinal investigation of self-reported risky driving behaviours, such as GDL-specific and general road rule compliance; risky behaviour such as pre-Licence driving, crash involvement and offence detection; and vehicle ownership, paying attention to Police presence, and punishment avoidance. Whilst the majority of Learner and Provisional drivers reported compliance with GDL-specific and general road rules, 33% of Learners and 50% of Provisional drivers reported speeding by 10-20 km/hr at least occasionally. Twelve percent of Learner drivers reported pre-Licence driving, and these drivers were significantly more risky as Learner and Provisional drivers. Ten percent of males and females reported being involved in a crash, and 10% of females and 18% of males had been detected for an offence, within the first six months of independent driving. Additionally, 75% of young novice drivers reported owning their own car within six months of gaining their Provisional driver's licence. Vehicle owners reported significantly shorter Learner periods and more risky driving exposure as a Provisional driver. Paying attention to Police presence on the roads appeared normative for young novice drivers: 91% of Learners and 72% of Provisional drivers reported paying attention. Provisional drivers also reported they actively avoided the Police: 25% of males and 13% of females; 23% of rural drivers and 15% of urban drivers. Stage Three also allowed the refinement of the risky behaviour measurement tool (BYNDS) created in Stage One; the original reliable 44-item instrument was refined to a similarly reliable 36-item instrument. A longitudinal exploration of the influence of anxiety, depression, sensation seeking propensity and reward sensitivity upon the risky behaviour of the Provisional driver was also undertaken using data collected in Stages Two and Three. Consistent with the research of Stage One, structural equation modeling revealed anxiety, reward sensitivity and sensation seeking propensity predicted self-reported risky driving behaviour. Again, gender was a moderator, with only reward sensitivity predicting risky driving for males. A measurement model of Akers' social learning theory (SLT) was developed containing six subscales operationalising the four constructs of differential association, imitation, personal attitudes, and differential reinforcement, and the influence of parents and peers was captured within the items in a number of these constructs. Analyses exploring the nature and extent of the psychosocial influences of personal characteristics (step 1), Akers' SLT (step 2), and elements of the prototype/willingness model (PWM) (step 3) upon self-reported speeding by the Provisional driver in a hierarchical multiple regression model found the following significant predictors: gender (male), car ownership (own car), reward sensitivity (greater sensitivity), depression (greater depression), personal attitudes (more risky attitudes), and speeding (more speeding) as a Learner. The research findings have considerable implications for road safety researchers, policy-makers, mental health professionals and medical practitioners alike. A broad range of issues need to be considered when developing, implementing and evaluating interventions for both the intentional and unintentional risky driving behaviours of interest. While a variety of interventions have been historically utilised, including education, enforcement, rehabilitation and incentives, caution is warranted. A multi-faceted approach to improving novice road safety is more likely to be effective, and new and existing countermeasures should capitalise on the potential of parents, peers and Police to be a positive influence upon the risky behaviour of young novice drivers. However, the efficacy of some interventions remains undetermined at this time. Notwithstanding this caveat, countermeasures such as augmenting and strengthening Queensland's GDL program and targeting parents and adolescents particularly warrant further attention. The findings of the research program suggest that Queensland's current-GDL can be strengthened by increasing compliance of young novice drivers with existing conditions and restrictions. The rates of speeding reported by the young Learner driver are particularly alarming for a number of reasons. The Learner is inexperienced in driving, and travelling in excess of speed limits places them at greater risk as they are also inexperienced in detecting and responding appropriately to driving hazards. In addition, the Learner period should provide the foundation for a safe lifetime driving career, enabling the development and reinforcement of non-risky driving habits. Learners who sped reported speeding by greater margins, and at greater frequencies, when they were able to drive independently. Other strategies could also be considered to enhance Queensland's GDL program, addressing both the pre-Licence adolescent and their parents. Options that warrant further investigation to determine their likely effectiveness include screening and treatment of novice drivers by mental health professionals and/or medical practitioners; and general social skills training. Considering the self-reported pre-licence driving of the young novice driver, targeted education of parents may need to occur before their child obtains a Learner licence. It is noteworthy that those participants who reported risky driving during the Learner phase also were more likely to report risky driving behaviour during the Provisional phase; therefore it appears vital that the development of safe driving habits is encouraged from the beginning of the novice period. General education of parents and young novice drivers should inform them of the considerably-increased likelihood of risky driving behaviour, crashes and offences associated with having unlimited access to a vehicle in the early stages of intermediate licensure. Importantly, parents frequently purchase the car that is used by the Provisional driver, who typically lives at home with their parents, and therefore parents are ideally positioned to monitor the journeys of their young novice driver during this early stage of independent driving. Parents are pivotal in the development of their driving child: they are models who are imitated and are sources of attitudes, expectancies, rewards and punishments; and they provide the most driving instruction for the Learner. High rates of self-reported speeding by Learners suggests that GDL programs specifically consider the nature of supervision during the Learner period, encouraging supervisors to be vigilant to compliance with general and GDL-specific road rules, and especially driving in excess of speed limit. Attitudes towards driving are formed before the adolescent reaches the age when they can be legally licensed. Young novice drivers with risky personal attitudes towards driving reported more risky driving behaviour, suggesting that countermeasures should target such attitudes and that such interventions might be implemented before the adolescent is licensed. The risky behaviours and attitudes of friends were also found to be influential, and given that young novice drivers tend to carry their friends as their passengers, a group intervention such as provided in a school class context may prove more effective. Social skills interventions that encourage the novice to resist the negative influences of their friends and their peer passengers, and to not imitate the risky driving behaviour of their friends, may also be effective. The punishments and rewards anticipated from and administered by friends were also found to influence the self-reported risky behaviour of the young novice driver; therefore young persons could be encouraged to sanction the risky, and to reward the non-risky, driving of their novice friends. Adolescent health programs and related initiatives need to more specifically consider the risks associated with driving. Young novice drivers are also adolescents, a developmental period associated with depression and anxiety. Depression, anxiety, and sensation seeking propensity were found to be predictive of risky driving; therefore interventions targeting psychological distress, whilst discouraging the expression of sensation seeking propensity whilst driving, warrant development and trialing. In addition, given that reward sensitivity was also predictive, a scheme which rewards novice drivers for safe driving behaviour - rather than rewarding the novice through emotional and instrumental rewards for risky driving behaviour - requires further investigation. The Police were also influential in the risky driving behaviour of young novices. Young novice drivers who had been detected for an offence, and then avoided punishment, reacted differentially, with some drivers appearing to become less risky after the encounter, whilst for others their risky behaviour appeared to be reinforced and therefore was more likely to be performed again. Such drivers saw t

Dissection of class III major histocompatibility complex haplotypes associated with rheumatoid arthritis

Objective. We have previously identified a single-nucleotide polymorphism (SNP) haplotype involving the lymphotoxin α (LTA) and tumor necrosis factor (TNF) loci (termed haplotype LTA-TNF2) on chromosome 6 that shows differential association with rheumatoid arthritis (RA) on HLA-DRB1*0404 and *0401 haplotypes, suggesting the presence of additional non-HLA-DRB1 RA susceptibility genes on these haplotypes. To refine this association, we performed a case-control association study using both SNPs and microsatellite markers in haplotypes matched either for HLA-DRB1*0404 or for HLA-DRB1*0401. Methods. Fourteen SNPs lying between HLA-DRB1 and LTA were genotyped in 87 DRB1*04-positive families. High-density microsatellite typing was performed using 24 markers spanning 2,500 kb centered around the TNF gene in 305 DRB1*0401 or *0404 cases and 400 DRB1*0401 or *0404 controls. Single-marker, 2-marker, and 3-marker minihaplotypes were constructed and their frequencies compared between the DRB1*0401 and DRB1*0404 matched case and control haplotypes. Results. Marked preservation of major histocompatibility complex haplotypes was seen, with chromosomes carrying LTA-TNF2 and either DRB1*0401 or DRB1*0404 both carrying an identical SNP haplotype across the 1-Mb region between TNF and HLA-DRB1. Using microsatellite markers, we observed two 3-marker minihaplotypes that were significantly overrepresented in the DRB1*0404 case haplotypes (P = 0.00024 and P = 0.00097). Conclusion. The presence of a single extended SNP haplotype between LTA-TNF2 and both DRB1*0401 and DRB1*0404 is evidence against this region harboring the genetic effects in linkage disequillbrium with LTA-TNF2. Two RA-associated haplotypes on the background of DRB1*0404 were identified in a 126-kb region surrounding and centromeric to the TNF locus.

Genetics of ankylosing spondylitis

Purpose of Review Over the past 3 years, several new genes and gene deserts have been identified that are associated with ankylosing spondylitis (AS). The purpose of this review is to discuss the major findings of these studies, and the answers they provide and questions they raise about the pathogenesis of this common condition. Recent Findings: Five genes/genetic regions have now definitively been associated with AS [the major histocompatibility complex (MHC), IL23R, ERAP1, 2p15 and 21q22]. Strong evidence to support association with the disease has been demonstrated for the genes IL1R2, ANTXR2, TNFSF15, TNFR1 and a region on chromosome 16q including the gene TRADD. There is an overrepresentation of genes involved in Th17 lymphocyte differentiation/activation among genes associated with AS and the related diseases inflammatory bowel disease and psoriasis, pointing strongly to this pathway as playing a major causative role in the disease. Increasing information about differential association of HLA-B27 subtypes with disease suggests a hierarchy of strength of association of those alleles with AS, providing a useful test as to the validity of different potential mechanisms of association of HLA-B27 with AS. The mechanism underlying the association of the gene deserts, 2p15 and 21q22, suggests the involvement of noncoding RNA in AS etiopathogenesis. Summary: The increasing list of genes identified as being definitely involved in AS provides a useful platform for hypothesis-driven research in the field, providing a potential alternative route to determining the underlying mechanisms involved in the disease to research focusing on HLA-B27 alone.

Perceptions on the causes of individual and fraudulent co-offending: Views of forensic accountants

Individual and/or co-offenders fraudulent activities can have a devastating effect on a company’s reputation and credibility. Enron, Xerox, WorldCom, HIH Insurance and One.Tel are examples where stakeholders incurred substantial financial losses as a result of fraud and led to a loss of confidence in corporate dealings by the public in general. There are numerous theoretical approaches that attempt to explain how and why fraudulent acts occur, drawing on the fields of sociology, organisational, management and economic literature, but there is limited empirical evidence published in accounting literature. This qualitative inductive study analyses perceptions and experiences of forensic accountants to gain insights into individual fraud and co-offending in order to determine whether the conceptual framework developed from literature accurately depicts the causes of fraud committed by individuals and groups in the twenty-first century. Findings from the study both support and extend the conceptual framework, demonstrating that strain and anomie can result in fraud, that deviant sub-groups recruit and coerce members by providing relief from strain, and that inadequate corporate governance mechanisms both contribute to fraud occurring, and provide the opportunity for fraudulent activities to be executed and often remain undetected. Additional factors emerging from this study (the ‘technoconomy’, addiction and IT measures) were also identified as contributors to fraud, particularly relevant to the twenty-first century, and consequently, a refined conceptual framework is presented in the discussion and conclusion to the paper.

Discrimination or Differential Involvement? A Review of the Research Exploring the Impact of Indigenous Status on Sentencing

Existing court data suggest that adult Indigenous offenders are more likely than non-Indigenous defendants to be sentenced to prison but once imprisoned generally receive shorter terms. Using findings from international and Australian multivariate statistical analyses, this paper reviews the three key hypotheses advanced as plausible explanations for these differences: 1) differential involvement, 2) negative discrimination, 3) positive discrimination. Overall, prior research shows strong support for the differential involvement thesis, some support for positive discrimination and little foundation for negative discrimination in the sentencing of Indigenous defendants. Where discrimination is found, we argue that this may be explained by the lack of a more complete set of control variables in researchers’ multivariate models.

Using optical coherence tomography for differential diagnosis of a pigmented choroidal lesion

Clinicians regularly face the confronting challenge of differentiating a choroidal naevus from a melanoma. Uveal naevi are a relatively common finding during routine eye examinations: a prevalence of 6.5 per cent has been reported.1 In contrast, malignant melanomata are uncommon, being found in six persons per million population, but they can have devastating implications and consequences.2 Differential diagnoses can be difficult to make with certainty; any additional information that can assist in this process is advantageous...

The association of single nucleotide polymorphisms with endometrial cancer risk and prognosis

Endometrial cancer is one of the most common female diseases in developed nations and is the most commonly diagnosed gynaecological cancer in Australia. The disease is commonly classified by histology: endometrioid or non-endometrioid endometrial cancer. While non-endometrioid endometrial cancers are accepted to be high-grade, aggressive cancers, endometrioid cancers (comprising 80% of all endometrial cancers diagnosed) generally carry a favourable patient prognosis. However, endometrioid endometrial cancer patients endure significant morbidity due to surgery and radiotherapy used for disease treatment, and patients with recurrent disease have a 5-year survival rate of less than 50%. Genetic analysis of women with endometrial cancer could uncover novel markers associated with disease risk and/or prognosis, which could then be used to identify women at high risk and for the use of specialised treatments. Proteases are widely accepted to play an important role in the development and progression of cancer. This PhD project hypothesised that SNPs from two protease gene families, the matrix metalloproteases (MMPs, including their tissue inhibitors, TIMPs) and the tissue kallikrein-related peptidases (KLKs) would be associated with endometrial cancer susceptibility and/or prognosis. In the first part of this study, optimisation of the genotyping techniques was performed. Results from previously published endometrial cancer genetic association studies were attempted to be validated in a large, multicentre replication set (maximum cases n = 2,888, controls n = 4,483, 3 studies). The rs11224561 progesterone receptor SNP (PGR, A/G) was observed to be associated with increased endometrial cancer risk (per A allele OR 1.31, 95% CI 1.12-1.53; p-trend = 0.001), a result which was initially reported among a Chinese sample set. Previously reported associations for the remaining 8 SNPs investigated for this section of the PhD study were not confirmed, thereby reinforcing the importance of validation of genetic association studies. To examine the effect of SNPs from the MMP and KLK families on endometrial cancer risk, we selected the most significantly associated MMP and KLK SNPs from genome-wide association study analysis (GWAS) to be genotyped in the GWAS replication set (cases n = 4,725, controls n = 9,803, 13 studies). The significance of the MMP24 rs932562 SNP was unchanged after incorporation of the stage 2 samples (Stage 1 per allele OR 1.18, p = 0.002; Combined Stage 1 and 2 OR 1.09, p = 0.002). The rs10426 SNP, located 3' to KLK10 was predicted by bioinformatic analysis to effect miRNA binding. This SNP was observed in the GWAS stage 1 result to exhibit a recessive effect on endometrial cancer risk, a result which was not validated in the stage 2 sample set (Stage 1 OR 1.44, p = 0.007; Combined Stage 1 and 2 OR 1.14, p = 0.08). Investigation of the regions imputed surrounding the MMP, TIMP and KLK genes did not reveal any significant targets for further analysis. Analysis of the case data from the endometrial cancer GWAS to identify genetic variation associated with cancer grade did not reveal SNPs from the MMP, TIMP or KLK genes to be statistically significant. However, the representation of SNPs from the MMP, TIMP and KLK families by the GWAS genotyping platform used in this PhD project was examined and observed to be very low, with the genetic variation of four genes (MMP23A, MMP23B, MMP28 and TIMP1) not captured at all by this technique. This suggests that comprehensive candidate gene association studies will be required to assess the role of SNPs from these genes with endometrial cancer risk and prognosis. Meta-analysis of gene expression microarray datasets curated as part of this PhD study identified a number of MMP, TIMP and KLK genes to display differential expression by endometrial cancer status (MMP2, MMP10, MMP11, MMP13, MMP19, MMP25 and KLK1) and histology (MMP2, MMP11, MMP12, MMP26, MMP28, TIMP2, TIMP3, KLK6, KLK7, KLK11 and KLK12). In light of these findings these genes should be prioritised for future targeted genetic association studies. Two SNPs located 43.5 Mb apart on chromosome 15 were observed from the GWAS analysis to be associated with increased endometrial cancer grade, results that were validated in silico in two independent datasets. One of these SNPs, rs8035725 is located in the 5' untranslated region of a MYC promoter binding protein DENND4A (Stage 1 OR 1.15, p = 9.85 x 10P -5 P, combined Stage 1 and in silico validation OR 1.13, p = 5.24 x 10P -6 P). This SNP has previously been reported to alter the expression of PTPLAD1, a gene involved in the synthesis of very long fatty acid chains and in the Rac1 signaling pathway. Meta-analysis of gene expression microarray data found PTPLAD1 to display increased expression in the aggressive non-endometrioid histology compared with endometrioid endometrial cancer, suggesting that the causal SNP underlying the observed genetic association may influence expression of this gene. Neither rs8035725 nor significant SNPs identified by imputation were predicted bioinformatically to affect transcription factor binding sites, indicating that further studies are required to assess their potential effect on other regulatory elements. The other grade- associated SNP, rs6606792, is located upstream of an inferred pseudogene, ELMO2P1 (Stage 1 OR 1.12, p = 5 x 10P -5 P; combined Stage 1 and in silico validation OR 1.09, p = 3.56 x 10P -5 P). Imputation of the ±1 Mb region surrounding this SNP revealed a cluster of significantly associated variants which are predicted to abolish various transcription factor binding sites, and would be expected to decrease gene expression. ELMO2P1 was not included on the microarray platforms collected for this PhD, and so its expression could not be investigated. However, the high sequence homology of ELMO2P1 with ELMO2, a gene important to cell motility, indicates that ELMO2 could be the parent gene for ELMO2P1 and as such, ELMO2P1 could function to regulate the expression of ELMO2. Increased expression of ELMO2 was seen to be associated with increasing endometrial cancer grade, as well as with aggressive endometrial cancer histological subtypes by microarray meta-analysis. Thus, it is hypothesised that SNPs in linkage disequilibrium with rs6606792 decrease the transcription of ELMO2P1, reducing the regulatory effect of ELMO2P1 on ELMO2 expression. Consequently, ELMO2 expression is increased, cell motility is enhanced leading to an aggressive endometrial cancer phenotype. In summary, these findings have identified several areas of research for further study. The results presented in this thesis provide evidence that a SNP in PGR is associated with risk of developing endometrial cancer. This PhD study also reports two independent loci on chromosome 15 to be associated with increased endometrial cancer grade, and furthermore, genes associated with these SNPs to be differentially expressed according in aggressive subtypes and/or by grade. The studies reported in this thesis support the need for comprehensive SNP association studies on prioritised MMP, TIMP and KLK genes in large sample sets. Until these studies are performed, the role of MMP, TIMP and KLK genetic variation remains unclear. Overall, this PhD study has contributed to the understanding of genetic variation involvement in endometrial cancer susceptibility and prognosis. Importantly, the genetic regions highlighted in this study could lead to the identification of novel gene targets to better understand the biology of endometrial cancer and also aid in the development of therapeutics directed at treating this disease.

Differential regulation of growth and invasiveness of MCF-7 breast cancer cells by antiestrogens

Estrogen increases the ability of the estrogen-dependent MCF-7 human breast cancer cell line to both proliferate and invade through an artificial basement membrane. In studying the response of MCF-7 cells to various antiestrogens, we found that 4-hydroxytamoxifen and tamoxifen inhibited cell proliferation but increased their invasiveness. In contrast, the structurally unrelated benzothiophene antiestrogens, LY117018 and LY156758, were potent antiproliferative agents which did not stimulate invasiveness. The differential effects of these antiestrogenic agents on invasion correlated with changes in production of collagenase IV, while no significant change was seen in the chemotactic activity of the cells. Invasiveness was increased by 17β-estradiol or 4-hydroxytamoxifen after a few hours of treatment and was rapidly lost when 17β-estradiol was withdrawn. Stimulation of invasiveness with 17β-estradiol was blocked by the antiestrogen, LY117018. Cells from the MDA-MB-231 line which lacks estrogen receptors were not affected by estrogen or antiestrogen in terms of proliferation or invasion. These studies indicate that the invasiveness of MCF-7 cells is regulated by antiestrogens through the estrogen receptor and may be mediated by collagenase IV activity. Antiestrogens which reduce both the proliferation and invasiveness of these cells may be interesting new candidates for clinical application.

Differential effects of refractive blur on day and night-time driving performance

Purpose To investigate the effect of different levels of refractive blur on real-world driving performance measured under day and nighttime conditions. Methods Participants included 12 visually normal, young adults (mean age = 25.8 ± 5.2 years) who drove an instrumented research vehicle around a 4 km closed road circuit with three different levels of binocular spherical refractive blur (+0.50 diopter sphere [DS], +1.00 DS, +2.00 DS) compared with a baseline condition. The subjects wore optimal spherocylinder correction and the additional blur lenses were mounted in modified full-field goggles; the order of testing of the blur conditions was randomized. Driving performance was assessed in two different sessions under day and nighttime conditions and included measures of road signs recognized, hazard detection and avoidance, gap detection, lane-keeping, sign recognition distance, speed, and time to complete the course. Results Refractive blur and time of day had significant effects on driving performance (P < 0.05), where increasing blur and nighttime driving reduced performance on all driving tasks except gap judgment and lane keeping. There was also a significant interaction between blur and time of day (P < 0.05), such that the effects of blur were exacerbated under nighttime driving conditions; performance differences were evident even for +0.50 DS blur relative to baseline for some measures. Conclusions The effects of blur were greatest under nighttime conditions, even for levels of binocular refractive blur as low as +0.50 DS. These results emphasize the importance of accurate and up-to-date refractive correction of even low levels of refractive error when driving at night.

Differential processing of thematic and categorical conceptual relations in spoken word production

Studies of semantic context effects in spoken word production have typically distinguished between categorical (or taxonomic) and associative relations. However, associates tend to confound semantic features or morphological representations, such as whole-part relations and compounds (e.g., BOAT-anchor, BEE-hive). Using a picture-word interference paradigm and functional magnetic resonance imaging (fMRI), we manipulated categorical (COW-rat) and thematic (COW-pasture) TARGET-distractor relations in a balanced design, finding interference and facilitation effects on naming latencies, respectively, as well as differential patterns of brain activation compared with an unrelated distractor condition. While both types of distractor relation activated the middle portion of the left middle temporal gyrus (MTG) consistent with retrieval of conceptual or lexical representations, categorical relations involved additional activation of posterior left MTG, consistent with retrieval of a lexical cohort. Thematic relations involved additional activation of the left angular gyrus. These results converge with recent lesion evidence implicating the left inferior parietal lobe in processing thematic relations and may indicate a potential role for this region during spoken word production.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

Aims/hypothesis Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study. Methods Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot. Results The top ranked variant was rs3805931 with p = 2.66 × 10−7, but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10−5) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10−8). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina. Conclusions/interpretation Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.