The Three Drivers of Innovation

Innovation can be triggered by problems, constraints and opportunities. This paper discusses the different challenges related to these three drivers and how contemporary Business Process Management and Enterprise Architecture solutions can address these. A number of case studies show how proactive forms of innovation can be facilitated.

Clusterin is a critical downstream mediator of stress-induced YB-1 transactivation in prostate cancer

Clusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer. Mol Cancer Res; 9(12); 1755–66.

Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript

Abstract Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P = 3.9 × 10−22). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P = 1.9 × 10−34). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk.

Risk taking by motorcyclists : rider training and stages of change

Motorcyclists in Australia have been found to be 30 times more likely to be killed per kilometre travelled than car occupants and 40 times more likely to be seriously injured. One approach to preventing motorcycle-related injury is through training and education. While there is traditionally a major focus on developing riding skills during training for motorcyclists, there is also a need for training to promote safe riding to reduce subsequent risk taking. The Transtheoretical Model, commonly known as the ‘Stages of Change’ model, provides a rationale to support incremental behaviour change for risky riding that may be facilitated through motorcycle rider training and education. A sample of 438 learner motorcyclists attended a rider training program in Queensland, Australia, with the stages of change to adopt a safe riding mindset and safe riding practices being measured upon commencement of the course (Time 1) and then again upon completion (Time 2). A small subset of the original sample (n=45) responded at follow up 24 months post training (Time 3). Consistent with the aims of training, results showed a significant shift from the contemplation stage to the subsequent stages of change for participants between Time 1 and Time 2. Progression to the later stages in the model was found for the subset of participants that responded at the Time 3 follow up. Issues of questionnaire design and the utility of the Transtheoretical Model for motorcycle rider training are discussed.

Numerical solution of stress intensity factors of multiple cracks in great number with eigen COD boundary integral equations

Based on the eigen crack opening displacement (COD) boundary integral equations, a newly developed computational approach is proposed for the analysis of multiple crack problems. The eigen COD particularly refers to a crack in an infinite domain under fictitious traction acting on the crack surface. With the concept of eigen COD, the multiple cracks in great number can be solved by using the conventional displacement discontinuity boundary integral equations in an iterative fashion with a small size of system matrix. The interactions among cracks are dealt with by two parts according to the distances of cracks to the current crack. The strong effects of cracks in adjacent group are treated with the aid of the local Eshelby matrix derived from the traction BIEs in discrete form. While the relatively week effects of cracks in far-field group are treated in the iteration procedures. Numerical examples are provided for the stress intensity factors of multiple cracks, up to several thousands in number, with the proposed approach. By comparing with the analytical solutions in the literature as well as solutions of the dual boundary integral equations, the effectiveness and the efficiencies of the proposed approach are verified.

A qualitative think aloud study of the early Neo-Piagetian stages of reasoning in novice programmers

Recent research indicates that some of the difficulties faced by novice programmers are manifested very early in their learning. In this paper, we present data from think aloud studies that demonstrate the nature of those difficulties. In the think alouds, novices were required to complete short programming tasks which involved either hand executing ("tracing") a short piece of code, or writing a single sentence describing the purpose of the code. We interpret our think aloud data within a neo-Piagetian framework, demonstrating that some novices reason at the sensorimotor and preoperational stages, not at the higher concrete operational stage at which most instruction is implicitly targeted.

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

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.

Drying condition effects on fluidization quality and fluidization velocity at initial and final stages of cubical particulates for pet food

In this research fluidization behavior of cubical Bovine intestine samples was studied. Bovine intestine samples were heat pump dried at atmospheric pressure and at emperatures below and above the material freezing points. Experiments were conducted to study fluidization characteristics and drying kinetics at different drying conditions. Bovine particles were characterized according to Geldart classification and minimum fluidization velocity was calculated using Ergun Equation and generalized equation for all drying conditions at the beginning of the trials and end of the trials. Walli’s model was used to categorize stability of the fluidization at the beginning and end of the drying for each trial. Walli’s values determined were positive at the beginning and end of all trials indicating stable fluidisation at the beginning and end for each drying condition.

Three sketches of a favourite cat

Poem

Early stages of growth of YBa2Cu3O7-δ high Tc superconducting films on (001) Y-ZrO2 substrates

The early stages of growth of high quality YBa2Cu 3O7-δ (YBCO) films grown on (001) Y-ZrO2 (YSZ) substrates by pulsed laser deposition have been studied using a combination of atomic force microscopy and transmission electron microscopy. A one unit cell thick YBCO layer and relatively large CuO particles formed in the initial stages. Additional YBCO grew on top of the first layer in the form of one or a few unit cell high c-axis oriented islands about 30 nm in diameter. The rounded islands subsequently coalesced into faceted domains. Elongated Y 2BaCuO5 particles nucleated after the first layer of YBCO. A highly textured BaZrO3 layer formed between the YSZ and the YBCO with a cube-on-cube dominant orientation relationship with respect to the YBCO film.

Regulation of the Fear Network by Mediators of Stress: Norepinephrine Alters the Balance between Cortical and Subcortical Afferent Excitation of the Lateral Amygdala

Pavlovian auditory fear conditioning involves the integration of information about an acoustic conditioned stimulus (CS) and an aversive unconditioned stimulus in the lateral nucleus of the amygdala (LA). The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE), regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased toward the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance toward the faster but more primitive subcortical input