Timing of births and endometrial cancer risk in Swedish women

While a protective long-term effect of parity on endometrial cancer risk is well established, the impact of timing of births is not fully understood. We examined the relationship between endometrial cancer risk and reproductive characteristics in a population-based cohort of 2,674,465 Swedish women, 20–72 years of age. During follow-up from 1973 through 2004, 7,386 endometrial cancers were observed. Compared to uniparous women, nulliparous women had a significantly elevated endometrial cancer risk (hazard ratio [HR] = 1.32, 95% confidence interval [CI], 1.22–1.42). Endometrial cancer risk decreased with increasing parity; compared to uniparous women, women with ≥4 births had a HR=0.66 (95% CI, 0.59–0.74); p-trend < 0.001. Among multiparous women, we observed no relationship of risk with age at first birth after adjustment for other reproductive factors. While we initially observed a decreased risk with later ages at last birth, this appeared to reflect a stronger relationship with time since last birth, with women with shorter times being at lowest risk. In models for multiparous women that included number of births, age at first and last birth, and time since last birth, age at last birth was not associated with endometrial cancer risk, while shorter time since last birth and increased parity were associated with statistically significantly reduced endometrial cancer risks. The HR was 3.95 (95%CI; 2.17–7.20; p-trend=<0.0001) for women with ≥25 years since a last birth compared to women having given birth within 4 years. Our findings support that clearance of initiated cells during delivery may be important in endometrial carcinogenesis. Keywords: endometrial carcinoma, parity, registry, reproductive factors

Four characters stuck inside a mystery [Review]

IN Harold Pinter's No Man's Land, four Englishmen find themselves trapped in a strange sort of limbo in the library of a well-to-do-house with musty old books, far too many bottles of beer, wine and spirits, dusty lamps and memories that never quite match up.

Stop and revive? : the effectiveness of nap and active rest breaks for reducing driver sleepiness

The incidence of sleep-related crashes has been estimated to account for approximately 20% of all fatal and severe crashes. The use of sleepiness countermeasures by drivers is an important component to reduce the incidence rates of sleep-related crashes. Taking a brief nap and stopping for a rest break are two highly publicised countermeasures for driver sleepiness and are also believed by drivers to be the most effective countermeasures. Despite this belief, there is scarce evidence to support the utility of these countermeasures for reducing driver sleepiness levels. Therefore, determining the effectiveness of these countermeasures is an important road safety concern. The current study utilised a young adult sample (N = 20) to investigate the effectiveness of a nap and an active rest break. The countermeasures effects were evaluated by physiological, behavioural (hazard perception skill), and subjective measures previously found sensitive to sleepiness. Participants initially completed two hours of a simulated driving task followed by a 15 minute nap opportunity or a 15 minute active rest break that included 10 minutes of brisk walking. After the break, participants completed one final hour of the simulated driving task. A within-subjects design was used so that each participant completed both the nap and the active rest break conditions on separate occasions. The analyses revealed that only the nap break provided any meaningful reduction in physiological sleepiness, reduced subjective sleepiness levels, and maintained hazard perception performance. In contrast, the active rest break had no effect for reducing physiological sleepiness and resulted in a decrement in hazard perception performance (i.e., an increase of reaction time latencies), with a transient reduction in subjective sleepiness levels. A number of theoretical, empirical and practical issues were identified by the current study.

Malnutrition and its impact on cost of hospitalization, length of stay, readmission and 3-year mortality

Background & aims: The confounding effect of disease on the outcomes of malnutrition using diagnosis-related groups (DRG) has never been studied in a multidisciplinary setting. This study aims to determine the prevalence of malnutrition in a tertiary hospital in Singapore and its impact on hospitalization outcomes and costs, controlling for DRG. Methods: This prospective cohort study included a matched case control study. Subjective Global Assessment was used to assess the nutritional status on admission of 818 adults. Hospitalization outcomes over 3 years were adjusted for gender, age, ethnicity, and matched for DRG. Results: Malnourished patients (29%) had longer hospital stays (6.9 ± 7.3 days vs. 4.6 ± 5.6 days, p < 0.001) and were more likely to be readmitted within 15 days (adjusted relative risk = 1.9, 95%CI 1.1–3.2, p = 0.025). Within a DRG, the mean difference between actual cost of hospitalization and the average cost for malnourished patients was greater than well-nourished patients (p = 0.014). Mortality was higher in malnourished patients at 1 year (34% vs. 4.1 %), 2 years (42.6% vs. 6.7%) and 3 years (48.5% vs. 9.9%); p < 0.001 for all. Overall, malnutrition was a significant predictor of mortality (adjusted hazard ratio = 4.4, 95% CI 3.3-6.0, p < 0.001). Conclusions: Malnutrition was evident in up to one third of the inpatients and led to poor hospitalization outcomes and survival as well as increased costs of care, even after matching for DRG. Strategies to prevent and treat malnutrition in the hospital and post-discharge are needed.

Modeling perceived collision risk in port water navigation

An increase in the likelihood of navigational collisions in port waters has put focus on the collision avoidance process in port traffic safety. The most widely used on-board collision avoidance system is the automatic radar plotting aid which is a passive warning system that triggers an alert based on the pilot’s pre-defined indicators of distance and time proximities at the closest point of approaches in encounters with nearby vessels. To better help pilot in decision making in close quarter situations, collision risk should be considered as a continuous monotonic function of the proximities and risk perception should be considered probabilistically. This paper derives an ordered probit regression model to study perceived collision risks. To illustrate the procedure, the risks perceived by Singapore port pilots were obtained to calibrate the regression model. The results demonstrate that a framework based on the probabilistic risk assessment model can be used to give a better understanding of collision risk and to define a more appropriate level of evasive actions.

Exposure to hot and cold temperatures and ambulance attendances in Brisbane, Australia: A time series study

ABSTRACT Objectives: To investigate the effect of hot and cold temperatures on ambulance attendances. Design: An ecological time series study. Setting and participants: The study was conducted in Brisbane, Australia. We collected information on 783 935 daily ambulance attendances, along with data of associated meteorological variables and air pollutants, for the period of 2000–2007. Outcome measures: The total number of ambulance attendances was examined, along with those related to cardiovascular, respiratory and other non-traumatic conditions. Generalised additive models were used to assess the relationship between daily mean temperature and the number of ambulance attendances. Results: There were statistically significant relationships between mean temperature and ambulance attendances for all categories. Acute heat effects were found with a 1.17% (95% CI: 0.86%, 1.48%) increase in total attendances for 1 °C increase above threshold (0–1 days lag). Cold effects were delayed and longer lasting with a 1.30% (0.87%, 1.73%) increase in total attendances for a 1 °C decrease below the threshold (2–15 days lag). Harvesting was observed following initial acute periods of heat effects, but not for cold effects. Conclusions: This study shows that both hot and cold temperatures led to increases in ambulance attendances for different medical conditions. Our findings support the notion that ambulance attendance records are a valid and timely source of data for use in the development of local weather/health early warning systems.

Exposure to hot and cold temperatures and ambulance attendances in Brisbane, Australia

Objectives: To investigate the effect of hot and cold temperatures on ambulance attendances. Design: An ecological time series study. Setting and participants: The study was conducted in Brisbane, Australia. We collected information on 783 935 daily ambulance attendances, along with data of associated meteorological variables and air pollutants, for the period of 2000–2007. Outcome measures: The total number of ambulance attendances was examined, along with those related to cardiovascular, respiratory and other non-traumatic conditions. Generalised additive models were used to assess the relationship between daily mean temperature and the number of ambulance attendances. Results: There were statistically significant relationships between mean temperature and ambulance attendances for all categories. Acute heat effects were found with a 1.17% (95% CI: 0.86%, 1.48%) increase in total attendances for 1 °C increase above threshold (0–1 days lag). Cold effects were delayed and longer lasting with a 1.30% (0.87%, 1.73%) increase in total attendances for a 1 °C decrease below the threshold (2–15 days lag). Harvesting was observed following initial acute periods of heat effects, but not for cold effects. Conclusions: This study shows that both hot and cold temperatures led to increases in ambulance attendances for different medical conditions. Our findings support the notion that ambulance attendance records are a valid and timely source of data for use in the development of local weather/health early warning systems.

Decision support for the safe design and operation of unmanned aircraft systems

Unmanned Aircraft Systems (UAS) describe a diverse range of aircraft that are operated without a human pilot on-board. Unmanned aircraft range from small rotorcraft, which can fit in the palm of your hand, through to fixed wing aircraft comparable in size to that of a commercial passenger jet. The absence of a pilot on-board allows these aircraft to be developed with unique performance capabilities facilitating a wide range of applications in surveillance, environmental management, agriculture, defence, and search and rescue. However, regulations relating to the safe design and operation of UAS first need to be developed before the many potential benefits from these applications can be realised. According to the International Civil Aviation Organization (ICAO), a Risk Management Process (RMP) should support all civil aviation policy and rulemaking activities (ICAO 2009). The RMP is described in International standard, ISO 31000:2009 (ISO, 2009a). This standard is intentionally generic and high-level, providing limited guidance on how it can be effectively applied to complex socio-technical decision problems such as the development of regulations for UAS. Through the application of principles and tools drawn from systems philosophy and systems engineering, this thesis explores how the RMP can be effectively applied to support the development of safety regulations for UAS. A sound systems-theoretic foundation for the RMP is presented in this thesis. Using the case-study scenario of a UAS operation over an inhabited area and through the novel application of principles drawn from general systems modelling philosophy, a consolidated framework of the definitions of the concepts of: safe, risk and hazard is made. The framework is novel in that it facilitates the representation of broader subjective factors in an assessment of the safety of a system; describes the issues associated with the specification of a system-boundary; makes explicit the hierarchical nature of the relationship between the concepts and the subsequent constraints that exist between them; and can be evaluated using a range of analytic or deliberative modelling techniques. Following the general sequence of the RMP, the thesis explores the issues associated with the quantified specification of safety criteria for UAS. A novel risk analysis tool is presented. In contrast to existing risk tools, the analysis tool presented in this thesis quantifiably characterises both the societal and individual risk of UAS operations as a function of the flight path of the aircraft. A novel structuring of the risk evaluation and risk treatment decision processes is then proposed. The structuring is achieved through the application of the Decision Support Problem Technique; a modelling approach that has been previously used to effectively model complex engineering design processes and to support decision-making in relation to airspace design. The final contribution made by this thesis is in the development of an airworthiness regulatory framework for civil UAS. A novel "airworthiness certification matrix" is proposed as a basis for the definition of UAS "Part 21" regulations. The outcome airworthiness certification matrix provides a flexible, systematic and justifiable method for promulgating airworthiness regulations for UAS. In addition, an approach for deriving "Part 1309" regulations for UAS is presented. In contrast to existing approaches, the approach presented in this thesis facilitates a traceable and objective tailoring of system-level reliability requirements across the diverse range of UAS operations. The significance of the research contained in this thesis is clearly demonstrated by its practical real world outcomes. Industry regulatory development groups and the Civil Aviation Safety Authority have endorsed the proposed airworthiness certification matrix. The risk models have also been used to support research undertaken by the Australian Department of Defence. Ultimately, it is hoped that the outcomes from this research will play a significant part in the shaping of regulations for civil UAS, here in Australia and around the world.

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.

Hospital outpatient responses to potential driving impairment due to prescribed medications

Driving and using prescription medicines that have the potential to impair driving is an emerging research area. To date it is characterised by a limited (although growing) number of studies and methodological complexities that make generalisations about impairment due to medications difficult. Consistent evidence has been found for the impairing effects of hypnotics, sedative antidepressants and antihistamines, and narcotic analgesics, although it has been estimated that as many as nine medication classes have the potential to impair driving (Alvarez & del Rio, 2000; Walsh, de Gier, Christopherson, & Verstraete, 2004). There is also evidence for increased negative effects related to concomitant use of other medications and alcohol (Movig et al., 2004; Pringle, Ahern, Heller, Gold, & Brown, 2005). Statistics on the high levels of Australian prescription medication use suggest that consumer awareness of driving impairment due to medicines should be examined. One web-based study has found a low level of awareness, knowledge and risk perceptions among Australian drivers about the impairing effects of various medications on driving (Mallick, Johnston, Goren, & Kennedy, 2007). The lack of awareness and knowledge brings into question the effectiveness of the existing countermeasures. In Australia these consist of the use of ancillary warning labels administered under mandatory regulation and professional guidelines, advice to patients, and the use of Consumer Medicines Information (CMI) with medications that are known to cause impairment. The responsibility for the use of the warnings and related counsel to patients primarily lies with the pharmacist when dispensing relevant medication. A review by the Therapeutic Goods Administration (TGA) noted that in practice, advice to patients may not occur and that CMI is not always available (TGA, 2002). Researchers have also found that patients' recall of verbal counsel is very low (Houts, Bachrach, Witmer, Tringali, Bucher, & Localio, 1998). With healthcare observed as increasingly being provided in outpatient conditions (Davis et al., 2006; Vingilis & MacDonald, 2000), establishing the effectiveness of the warning labels as a countermeasure is especially important. There have been recent international developments in medication categorisation systems and associated medication warning labels. In 2005, France implemented a four-tier medication categorisation and warning system to improve patients' and health professionals' awareness and knowledge of related road safety issues (AFSSAPS, 2005). This warning system uses a pictogram and indicates the level of potential impairment in relation to driving performance through the use of colour and advice on the recommended behaviour to adopt towards driving. The comparable Australian system does not indicate the severity level of potential effects, and does not provide specific guidelines on the attitude or actions that the individual should adopt towards driving. It is reliant upon the patient to be vigilant in self-monitoring effects, to understand the potential ways in which they may be affected and how serious these effects may be, and to adopt the appropriate protective actions. This thesis investigates the responses of a sample of Australian hospital outpatients who receive appropriate labelling and counselling advice about potential driving impairment due to prescribed medicines. It aims to provide baseline data on the understanding and use of relevant medications by a Queensland public hospital outpatient sample recruited through the hospital pharmacy. It includes an exploration and comparison of the effect of the Australian and French medication warning systems on medication user knowledge, attitudes, beliefs and behaviour, and explores whether there are areas in which the Australian system may be improved by including any beneficial elements of the French system. A total of 358 outpatients were surveyed, and a follow-up telephone survey was conducted with a subgroup of consenting participants who were taking at least one medication that required an ancillary warning label about driving impairment. A complementary study of 75 French hospital outpatients was also conducted to further investigate the performance of the warnings. Not surprisingly, medication use among the Australian outpatient sample was high. The ancillary warning labels required to appear on medications that can impair driving were prevalent. A subgroup of participants was identified as being potentially at-risk of driving impaired, based on their reported recent use of medications requiring an ancillary warning label and level of driving activity. The sample reported previous behaviour and held future intentions that were consistent with warning label advice and health protective action. Participants did not express a particular need for being advised by a health professional regarding fitness to drive in relation to their medication. However, it was also apparent from the analysis that the participants would be significantly more likely to follow advice from a doctor than a pharmacist. High levels of knowledge in terms of general principles about effects of alcohol, illicit drugs and combinations of substances, and related health and crash risks were revealed. This may reflect a sample specific effect. Emphasis is placed in the professional guidelines for hospital pharmacists that make it essential that advisory labels are applied to medicines where applicable and that warning advice is given to all patients on medication which may affect driving (SHPA, 2006, p. 221). The research program applied selected theoretical constructs from Schwarzer's (1992) Health Action Process Approach, which has extended constructs from existing health theories such as the Theory of Planned Behavior (Ajzen, 1991) to better account for the intention-behaviour gap often observed when predicting behaviour. This was undertaken to explore the utility of the constructs in understanding and predicting compliance intentions and behaviour with the mandatory medication warning about driving impairment. This investigation revealed that the theoretical constructs related to intention and planning to avoid driving if an effect from the medication was noticed were useful. Not all the theoretical model constructs that had been demonstrated to be significant predictors in previous research on different health behaviours were significant in the present analyses. Positive outcome expectancies from avoiding driving were found to be important influences on forming the intention to avoid driving if an effect due to medication was noticed. In turn, intention was found to be a significant predictor of planning. Other selected theoretical constructs failed to predict compliance with the Australian warning label advice. It is possible that the limited predictive power of a number of constructs including risk perceptions is due to the small sample size obtained at follow up on which the evaluation is based. Alternately, it is possible that the theoretical constructs failed to sufficiently account for issues of particular relevance to the driving situation. The responses of the Australian hospital outpatient sample towards the Australian and French medication warning labels, which differed according to visual characteristics and warning message, were examined. In addition, a complementary study with a sample of French hospital outpatients was undertaken in order to allow general comparisons concerning the performance of the warnings. While a large amount of research exists concerning warning effectiveness, there is little research that has specifically investigated medication warnings relating to driving impairment. General established principles concerning factors that have been demonstrated to enhance warning noticeability and behavioural compliance have been extrapolated and investigated in the present study. The extent to which there is a need for education and improved health messages on this issue was a core issue of investigation in this thesis. Among the Australian sample, the size of the warning label and text, and red colour were the most visually important characteristics. The pictogram used in the French labels was also rated highly, and was salient for a large proportion of the sample. According to the study of French hospital outpatients, the pictogram was perceived to be the most important visual characteristic. Overall, the findings suggest that the Australian approach of using a combination of visual characteristics was important for the majority of the sample but that the use of a pictogram could enhance effects. A high rate of warning recall was found overall and a further important finding was that higher warning label recall was associated with increased number of medication classes taken. These results suggest that increased vigilance and care are associated with the number of medications taken and the associated repetition of the warning message. Significantly higher levels of risk perception were found for the French Level 3 (highest severity) label compared with the comparable mandatory Australian ancillary Label 1 warning. Participants' intentions related to the warning labels indicated that they would be more cautious while taking potentially impairing medication displaying the French Level 3 label compared with the Australian Label 1. These are potentially important findings for the Australian context regarding the current driving impairment warnings about displayed on medication. The findings raise other important implications for the Australian labelling context. An underlying factor may be the differences in the wording of the warning messages that appear on the Australian and French labels. The French label explicitly states "do not drive" while the Australian label states "if affected, do not drive", and the difference in responses may reflect that less severity is perceived where the situation involves the consumer's self-assessment of their impairment. The differences in the assignment of responsibility by the Australian (the consumer assesses and decides) and French (the doctor assesses and decides) approaches for the decision to drive while taking medication raises the core question of who is most able to assess driving impairment due to medication: the consumer, or the health professional? There are pros and cons related to knowledge, expertise and practicalities with either option. However, if the safety of the consumer is the primary aim, then the trend towards stronger risk perceptions and more consistent and cautious behavioural intentions in relation to the French label suggests that this approach may be more beneficial for consumer safety. The observations from the follow-up survey, although based on a small sample size and descriptive in nature, revealed that just over half of the sample recalled seeing a warning label about driving impairment on at least one of their medications. The majority of these respondents reported compliance with the warning advice. However, the results indicated variation in responses concerning alcohol intake and modifying the dose of medication or driving habits so that they could continue to drive, which suggests that the warning advice may not be having the desired impact. The findings of this research have implications for current countermeasures in this area. These have included enhancing the role that prescribing doctors have in providing warnings and advice to patients about the impact that their medication can have on driving, increasing consumer perceptions of the authority of pharmacists on this issue, and the reinforcement of the warning message. More broadly, it is suggested that there would be benefit in a wider dissemination of research-based information on increased crash risk and systematic monitoring and publicity about the representation of medications in crashes resulting in injuries and fatalities. Suggestions for future research concern the continued investigation of the effects of medications and interactions with existing medical conditions and other substances on driving skills, effects of variations in warning label design, individual behaviours and characteristics (particularly among those groups who are dependent upon prescription medication) and validation of consumer self-assessment of impairment.

Applying Bayesian hierarchical models to examine motorcycle crashes at signalized intersections

Motorcycles are overrepresented in road traffic crashes and particularly vulnerable at signalized intersections. The objective of this study is to identify causal factors affecting the motorcycle crashes at both four-legged and T signalized intersections. Treating the data in time-series cross-section panels, this study explores different Hierarchical Poisson models and found that the model allowing autoregressive lag 1 dependent specification in the error term is the most suitable. Results show that the number of lanes at the four-legged signalized intersections significantly increases motorcycle crashes largely because of the higher exposure resulting from higher motorcycle accumulation at the stop line. Furthermore, the presence of a wide median and an uncontrolled left-turn lane at major roadways of four-legged intersections exacerbate this potential hazard. For T signalized intersections, the presence of exclusive right-turn lane at both major and minor roadways and an uncontrolled left-turn lane at major roadways of T intersections increases motorcycle crashes. Motorcycle crashes increase on high-speed roadways because they are more vulnerable and less likely to react in time during conflicts. The presence of red light cameras reduces motorcycle crashes significantly for both four-legged and T intersections. With the red-light camera, motorcycles are less exposed to conflicts because it is observed that they are more disciplined in queuing at the stop line and less likely to jump start at the start of green.

Factors affecting motorcycle crashes at signalized intersections

Singapore crash statistics show that motorcycles are involved in about 54% of crashes at intersections. Moreover, about 46% of fatal and 67% of injury motorcycle crashes occur at signalized intersections. The objective of this study is to identify causal factors affecting the motorcycle crashes at both four-legged and three-legged signalized intersections. Treating the data in time-series cross-section panels, this study explores different Hierarchical Poisson models and found that the model allowing autoregressive lag 1 dependent specification in the error term is the most suitable. Analysis of the results shows the number of lanes at the intersections significantly increases motorcycle crashes largely because of the higher exposure resulting from higher motorcycle accumulation at the stop line. Furthermore, the presence of a wide median at four-legged intersections and an exclusive right-turn lane and an uncontrolled left-turn lane at three-legged intersections exacerbate this potential hazard. Moreover, motorcycle crashes increase on high-speed roadways because of the vulnerability of the motorcyclists. The presence of red light cameras reduces motorcycle crashes significantly on the intersection roadways for both four-legged and three-legged intersections. With the red-light camera, motorcycles are less exposed to conflicts because it is observed that they are more disciplined in queuing at the stop line and less likely to jump start at the start of green.

FGFR2 point mutations in 466 Endometrioid Endometrial Tumors : relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and Clinicopathological features

Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies.

A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival. Results In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319). In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR) 1.42, 95% CI 1.02-1.96). This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34). This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site. Conclusions We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival.

Methodological challenges when estimating the effects of season and seasonal exposures on birth outcomes

Background Many previous studies have found seasonal patterns in birth outcomes, but with little agreement about which season poses the highest risk. Some of the heterogeneity between studies may be explained by a previously unknown bias. The bias occurs in retrospective cohorts which include all births occurring within a fixed start and end date, which means shorter pregnancies are missed at the start of the study, and longer pregnancies are missed at the end. Our objective was to show the potential size of this bias and how to avoid it. Methods To demonstrate the bias we simulated a retrospective birth cohort with no seasonal pattern in gestation and used a range of cohort end dates. As a real example, we used a cohort of 114,063 singleton births in Brisbane between 1 July 2005 and 30 June 2009 and examined the bias when estimating changes in gestation length associated with season (using month of conception) and a seasonal exposure (temperature). We used survival analyses with temperature as a time-dependent variable. Results We found strong artificial seasonal patterns in gestation length by month of conception, which depended on the end date of the study. The bias was avoided when the day and month of the start date was just before the day and month of the end date (regardless of year), so that the longer gestations at the start of the study were balanced by the shorter gestations at the end. After removing the fixed cohort bias there was a noticeable change in the effect of temperature on gestation length. The adjusted hazard ratios were flatter at the extremes of temperature but steeper between 15 and 25°C. Conclusions Studies using retrospective birth cohorts should account for the fixed cohort bias by removing selected births to get unbiased estimates of seasonal health effects.