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

The changing role of copyright in China’s emergent media economy

This chapter introduces the changing role of copyright in China from a historical perspective. It begins by briefly tracing the history of copyright, from a censorship-related system associated with the emergence of the printing press in imperial China, through modernisation during the Republican period, abolition under communism and finally to the introduction of the People's Republic of China's (PRC) first copyright law in 1990 and the nation's entry into the World Trade Organisation (WTO) in 2001.

Human milk xanthine oxidase and neonatal salivary nucleotide precursors generate hydrogen peroxide; a novel pathway with potential role in regulating oral microflora

Background: Xanthine oxidase (XO) is a complex molybdeno-flavoprotein occurring with high activity in the milk fat globule membrane (MFGM) in all mammalian milk and is involved in the final stage of degradation of purine nucleotides. It catalyzes the sequential oxidation of hypoxanthine to xanthine and uric acid, accompanied by production of hydrogen peroxide and superoxide anion. Human saliva has been extensively described for its composition of proteins, electrolytes, cortisol, melatonin and some metabolites such as amino acids, but little is known about nucleotide metabolites. Method: Saliva was collected with swabs from babies; at full-term 1-4 days, 6-weeks, 6-months and 12-months. Unstimulated fasting (morning) saliva samples were collected directly from 77 adults. Breast milk was collected from 24 new mothers. Saliva was extracted from swabs and ultra-filtered. Nucleotide metabolites were analyzed by RP-HPLC with UV-photodiode array and ESI-MS/MS. XO activity was measured as peroxide production from hypoxanthine. Bacterial inhibition over time was assessed using CFU/mL or OD. Results: Median concentrations (μmol/L) of salivary nucleobases and nucleosides for neonates/6-weeks/6-months/12-months/adult respectively were: uracil 5.3/0.8/1.4/0.7/0.8, hypoxanthine 27/7.0/1.1/0.8/2.0, xanthine 19/7.0/2.0/2.0/2.0, adenosine 12/7.0/0.9/0.8/0.1, inosine 11/5.0/0.3/0.4/0.2, guanosine 7.0/6.0/0.5/0.4/0.1, uridine 12/0.8/0.3/0.9/0.4. Deoxynucleosides and dihydropyrimidines concentrations were essentially negligible. XO activity (Vmax:mean ± SD) in breast milk was 8.9 ± 6.2 μmol/min/L and endogenous peroxide was 27 ± 12 μmol/L; mixing breast milk with neonate saliva generated ~40 μmol/L peroxide,which inhibited Staphylococcus aureus. Conclusions: Salivary metabolites, particularly xanthine/hypoxanthine, are high in neonates, transitioning to low adult levels between 6-weeks to 6-months (p < 0.001). Peroxide occurs in breast milk and is boosted during suckling as an antibacterial system.

Corporate governance and risk management : the role of risk management and compensation committees

This paper examines the role of compensation and risk committees in managing and monitoring the risk behaviour of Australian financial firms in the period leading up to the global financial crisis (2006–2008). This empirical study of 711 observations of financial sector firms demonstrates how the coordination of risk management and compensation committees reduces information asymmetry. The study shows that the composition of the risk and compensation committees is positively associated with risk, which, in turn, is associated with firm performance. More importantly, information asymmetry is reduced when a director is a member of both the risk and compensation committees which moderate the negative association between risk and firm performance for firms with high risk.

Cultural impact on e-service use in Saudi Arabia : the role of nepotism

This paper reports the results of a mixed method approach to answer: To what extent do cultural values impact on e-service use in Saudi Arabia, and if so how? This paper will firstly, introduce the importance of culture and define the aspects of Saudi culture. It will then describe the method used and present the questionnaire findings related to the role of nepotism. The review of the literature on nepotism indicates there is still much to be studied and learned. The legal aspects of nepotism, in addition to its impact on human resource management appear to be the more reported issues. However, nepotism’s impact on Information and Communication Technologies (ICT) has not been studied. This research aims to cover this gap by investigating to what extent nepotism, as one of Saudi Arabia’s cultural values, impacts on e-service use in Saudi Arabia. The tested hypothesis was found consistent with its predicted outcome: nepotism is a negative predictor of intention to use e- services in Saudi Arabia. It is evidenced that consideration of the impact of the cultural values will mainly contribute to the enhancement of social and organisational aspects of e-society research and practices, by deeply understanding them as of the influntials to e-service implementation.

Investigating homework as a social practice : a qualitative approach

This thesis examines the social practice of homework. It explores how homework is shaped by the discourses, policies and guidelines in circulation in a society at any given time with particular reference to one school district in the province of Newfoundland and Labrador, Canada. This study investigates how contemporary homework reconstitutes the home as a pedagogical site where the power of the institution of schooling circulates regularly from school to home. It examines how the educational system shapes the organization of family life and how family experiences with homework may be different in different sites depending on the accessibility of various forms of cultural capital. This study employs a qualitative approach, incorporating multiple case studies, and is complemented by insights from institutional ethnography and critical discourse analysis. It draws on the theoretical concepts of Foucault including power and power relations, and governmentality and surveillance, as well as Bourdieu’s concepts of economic, social and cultural capital for analysis. It employs concepts from Bourdieu’s work as they have been expanded on by researchers including Reay (1998), Lareau (2000), and Griffith and Smith (2005). The studies of these researchers allowed for an examination of homework as it related to families and mothers’ work. Smith’s (1987; 1999) concepts of ruling relations, mothers’ unpaid labour, and the engine of inequality were also employed in the analysis. Family interviews with ten volunteer families, teacher focus group sessions with 15 teachers from six schools, homework artefacts, school newsletters, homework brochures, and publicly available assessment and evaluation policy documents from one school district were analyzed. From this analysis key themes emerged and the findings are documented throughout five data analysis chapters. This study shows a change in education in response to a system shaped by standards, accountability and testing. It documents an increased transference of educational responsibility from one educational stakeholder to another. This transference of responsibility shifts downward until it eventually reaches the family in the form of homework and educational activities. Texts in the form of brochures and newsletters, sent home from school, make available to parents specific subject positions that act as instruments of normalization. These subject positions promote a particular ‘ideal’ family that has access to certain types of cultural capital needed to meet the school’s expectations. However, the study shows that these resources are not equally available to all and some families struggle to obtain what is necessary to complete educational activities in the home. The increase in transference of educational work from the school to the home results in greater work for parents, particularly mothers. As well, consideration is given to mother’s role in homework and how, in turn, classroom instructional practices are sometimes dependent on the work completed at home with differential effects for children. This study confirms previous findings that it is mothers who assume the greatest role in the educational trajectory of their children. An important finding in this research is that it is not only middle-class mothers who dedicate extensive time working hard to ensure their children’s educational success; working-class mothers also make substantial contributions of time and resources to their children’s education. The assignments and educational activities distributed as homework require parents’ knowledge of technical school pedagogy to help their children. Much of the homework being sent home from schools is in the area of literacy, particularly reading, but requires parents to do more than read with children. A key finding is that the practices of parents are changing and being reconfigured by the expectations of schools in regard to reading. Parents are now being required to monitor and supervise children’s reading, as well as help children complete reading logs, written reading responses, and follow up questions. The reality of family life as discussed by the participants in this study does not match the ‘ideal’ as portrayed in the educational documents. Homework sessions often create frustrations and tensions between parents and children. Some of the greatest struggles for families were created by mathematical homework, homework for those enrolled in the French Immersion program, and the work required to complete Literature, Heritage and Science Fair projects. Even when institutionalized and objectified capital was readily available, many families still encountered struggles when trying to carry out the assigned educational tasks. This thesis argues that homework and education-related activities play out differently in different homes. Consideration of this significance may assist educators to better understand and appreciate the vast difference in families and the ways in which each family can contribute to their children’s educational trajectory.

Trends in the Australian gender wage differential over the 1980s : some evidence on the effectiveness of legislative reform

The article examines the legislative reforms incorporating the Sex Discrimination Act and the Affirmative Action Act introduced during the 1980s. We utilise the Australian Bureau of Statistics Income Distribution Surveys 1981–82 and 1989–90 to reflect pre- and post-legislative reform. The article adopts the Brown, Moon and Zoloth (1980) methodology which treats both the wage and occupational status of the individual as endogenously determined. In the current context this is a particularly flexible framework allowing one to capture both the direct and indirect effects of the legislative reforms. The indirect effect refers to the narrowing of the gender wage gap associated with legislative manipulation of the male-female occupational distributions. The results contrast the slow convergence in the gender wage gap during the 1980s with the much faster pace of the 1970s. The article concludes that despite the focus of the 1980s legislation on employment equity, changes in the male-female occupational distribution over the period are small and the associated impact on gender wage convergence is also small.

Contemporaneous correlations within individuals in an automated web-based walking program (Walk@Work) over a six week period (three phases) of time

Introduction: Participants may respond to phases of a workplace walking program at different rates. This study evaluated the factors that contribute to the number of steps through phases of the program. The intervention was automated through a web-based program designed to increase workday walking. Methods: The study reviewed independent variable influences throughout phases I–III. A convenience sample of university workers (n=56; 43.6±1.7 years; BMI 27.44±.2.15 kg/m2; 48 female) were recruited at worksites in Australia. These workers were given a pedometer (Yamax SW 200) and access to the website program. For analyses, step counts entered by workers into the website were downloaded and mean workday steps were compared using a seemingly unrelated regression. This model was employed to capture the contemporaneous correlation within individuals in the study across observed time periods. Results: The model predicts that the 36 subjects with complete information took an average 7460 steps in the baseline two week period. After phase I, statistically significance increases in steps (from baseline) were explained by age, working status (full or part time), occupation (academic or professional), and self reported public transport (PT) use (marginally significant). Full time workers walked more than part time workers by about 440 steps, professionals walked about 300 steps more than academics, and PT users walked about 400 steps more than non-PT users. The ability to differentiate steps after two weeks among participants suggests a differential affect of the program after only two weeks. On average participants increased steps from week two to four by about 525 steps, but regular auto users had nearly 750 steps less than non-auto users at week four. The effect of age was diminished in the 4th week of observation and accounted for 34 steps per year of age. In phase III, discriminating between participants became more difficult, with only age effects differentiating their increase over baseline. The marginal effect of age by phase III compared to phase I, increased from 36 to 50, suggesting a 14 step per year increase from the 2nd to 6th week. Discussion: The findings suggest that participants responded to the program at different rates, with uniformity of effect achieved by the 6th week. Participants increased steps, however a tapering off occurred over time. Age played the most consistent role in predicting steps over the program. PT use was associated with increased step counts, while Auto use was associated with decreased step counts.

Organisational innovativeness : the role of strategic orientation and environmental scanning

This study examined the effects of strategic orientation and environmental scanning on a firm’s propensity to innovate (organisational innovativeness). Previous research has mostly proposed descriptive and theoretical relationships between strategic orientation, environmental scanning and organisational innovation adoption (Beal, 2000; Jennings & Lumpkin, 1992; Raymond, Julien, & Ramangalahy, 2001). However, strategic orientation and environmental scanning, as distinct constructs, have not been empirically examined directly before in relation to organisational innovativeness. Furthermore the directionality of the relationship between strategic orientation and environmental scanning on organisational innovation adoption is still unclear (Hagen, Haile, & Maghrabi, 2003). For example, does scanning the environment result in certain types of organisational strategies, and these strategies in turn influence levels of organisational innovativeness? Or do certain types of strategic orientations pre-determine the levels of environmental scanning, and then this environmental scanning influences an organisation’s propensity to innovate? Therefore, this study using a more nuanced measure of strategic orientation; the Venkatraman’s (1989) STROBE framework of analysis, defensiveness, futurity, proactiveness, aggressiveness and riskiness, examined the directional effects of strategy and environmental scanning on organisational innovativeness Specifically, two competing models of directionality between strategic orientation and environmental scanning in relation to organisational innovativeness were proposed. Model 1 (Behavioural View) proposed that certain strategic orientation dimensions affect levels of environmental scanning, which in turn influences organisational innovativeness. In contrast, Model 2 (Open Systems view) proposed that environmental scanning affects the emphasis on certain strategic orientation dimensions, which in turn influences organisational innovativeness. Data was collected from 117 industrial firms and path analyses were used to test the two competing models. The results supported both models, suggesting a bi-directional relationship, as both models had adequate fit indices and significant paths with the data. However, overall Model 2 – the Open Systems Model had the stronger fit indices and stronger indirect effect compared to Model 1 – the Behavioural Model, suggesting that overall environmental scanning does not exert a strong direct effect on innovativeness but has more of a stronger indirect effect through the analysis and proactiveness strategic orientation dimensions. In sum, the thesis results suggest that firms’ that emphasise environmental scanning – that is continually seeking information from the environment about customers, markets, industry and new technology - are more likely to emphasise strategic orientations such as proactiveness – being innovative - and also analysis – being analytical and comprehensive in decision making - and both these strategic orientations in turn greatly influence these firms’ propensity to innovate. Discussion is given to these findings and implications are drawn for organisations and future research.

The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib and ponatinib ATP-competitive inhibitors

We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confer resistance to the pan-FGFR inhibitor, dovitinib, and explore the mechanism of action of the drug-resistant mutations. We cultured BaF3 cells overexpressing FGFR2 in high concentrations of dovitinib and identified fourteen dovitinib-resistant mutations, including the N550K mutation observed in 25% of FGFR2mutant endometrial cancers (EC). Structural and biochemical in vitro kinase analyses, together with BaF3 proliferation assays, showed that the resistance mutations elevate the intrinsic kinase activity of FGFR2. BaF3 lines were used to assess the ability of each mutation to confer cross-resistance to PD173074 and ponatinib. Unlike PD173074, ponatinib effectively inhibited all the dovitinib-resistant FGFR2 mutants except the V565I gatekeeper mutation, suggesting ponatinib but not dovitinib targets the active conformation of FGFR2 kinase. EC cell lines expressing wild-type FGFR2 were relatively resistant to all inhibitors. Whereas EC cell lines expressing mutated FGFR2 showed differential sensitivity. Within the FGFR2mutant cell lines, 3/7 showed marked resistance to PD173074 and relative resistance to dovitinib and ponatinib. This suggests that alternative mechanisms distinct from kinase domain mutations are responsible for intrinsic resistance in these three EC lines. Finally, overexpression of FGFR2N550K in JHUEM-2 cells (FGFR2C383R) conferred resistance (~5 fold) to PD173074, providing independent data that FGFR2N550K can be associated with drug resistance. Biochemical in vitro kinase analyses also shows ponatinib is more effective than dovitinib at inhibiting FGFR2N550K. We propose tumors harboring mutationally activated FGFRs should be treated with FGFR inhibitors that specifically bind the active kinase.

Nurses’ role in caring for people with a comorbidity of mental illness and intellectual disability : A literature review

This article examines literature on the role of the nurse caring for people with a dual disability (DD) of intellectual disability and mental illness. A search of the literature between 2000 and 2010 resulted in a total of 21 articles that met the inclusion criteria. Seven key categories of the role of the nurse were identified: (i) advocacy/health promotion (including working with family); (ii) assessment/case management; (iii) behavioural interventions; (iv) communication; (v) leadership and the nurse’s role within the multidisciplinary team; (vi) functions regarding medication administration; and (vii) safety/risk management. There is a paucity of research about the role of nurses working with people with DD, although a number of opinion-based articles exist. This article identifies a need for the role of the nurse working in DD to be more clearly articulated and for the development of evidence to guide best practice.

L’internationalisation des jeunes entreprises de hautes technologies : Le rôle des compétences internationales des fondateurs [The internationalization of new technology based firms : the role of the international skills of founding teams]

Extending recent research on the importance of specific resources and skills for the internationalization of start-ups, this article tests a negative binomial model on a sample of 520 recently created high technology firms from the UK and Germany. The results show that previous international experience of entrepreneurs facilitates the rapid penetration of foreign markets, especially when the company features a clear and deliberate strategic intent of internationalization from the outset. This research provides one of the first empirical studies linking the influence of entrepreneurial teams to a high probability of success in the internationalization of high-technology ventures.

Technological innovation and operational effectiveness : their role in achieving performance improvements

The purpose of this article is to examine the role of the alignment between technological innovation effectiveness and operational effectiveness after the implementation of enterprise information systems, and the impact of this alignment on the improvement in operational performance. Confirmatory factor analysis was used to examine structural relationships between the set of observed variables and the set of continuous latent variables. The findings from this research suggest that the dimensions stemming from technological innovation effectiveness such as system quality, information quality, service quality, user satisfaction and the performance objectives stemming from operational effectiveness such as cost, quality, reliability, flexibility and speed are important and significantly well-correlated factors. These factors promote the alignment between technological innovation effectiveness and operational effectiveness and should be the focus for managers in achieving effective implementation of technological innovations. In addition, there is a significant and direct influence of this alignment on the improvement of operational performance. The principal limitation of this study is that the findings are based on investigation of small sample size.