Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumour xenografts regulate the NOTCH pathway

The use of adherent monolayer cultures have produced many insights into melanoma cell growth and differentiation, but often novel therapeutics demonstrated to act on these cells are not active in vivo. It is imperative that new methods of growing melanoma cells that reflect growth in vivo are investigated. To this end, a range of human melanoma cell lines passaged as adherent cultures or induced to form melanoma spheres (melanospheres) in stem cell media have been studied to compare cellular characteristics and protein expression. Melanoma spheres and tumours grown from cell lines as mouse xenografts had increased heterogeneity when compared with adherent cells and 3D-spheroids in agar (aggregates). Furthermore, cells within the melanoma spheres and mouse xenografts each displayed a high level of reciprocal BRN2 or MITF expression, which matched more closely the pattern seen in human melanoma tumours in situ, rather than the propensity for co-expression of these important melanocytic transcription factors seen in adherent cells and 3D-spheroids. Notably, when the levels of the BRN2 and MITF proteins were each independently repressed using siRNA treatment of adherent melanoma cells, members of the NOTCH pathway responded by decreasing or increasing expression, respectively. This links BRN2 as an activator, and conversely, MITF as a repressor of the NOTCH pathway in melanoma cells. Loss of the BRN2-MITF axis in antisense-ablated cell lines decreased the melanoma sphere-forming capability, cell adhesion during 3D-spheroid formation and invasion through a collagen matrix. Combined, this evidence suggests that the melanoma sphere-culture system induces subpopulations of cells that may more accurately portray the in vivo disease, than the growth as adherent melanoma cells.

Risk, trust, and consumer online purchasing behaviour : a Chilean perspective

Purpose: The purpose of this study is to investigate Latin American online purchase behaviour with a specific focus on the influence of perceived risk and trust. While studies of this nature have been conducted quite extensively in developed countries, their application in developing countries, such as Latin America is limited. Our study addresses this gap in the literature with an empirical study conducted in Chile. Design/methodology/approach: The authors develop and test a proposed model of the influence of consumer’s perceptions of risk and trust on their attitudes and intentions to purchase on the Internet. An online survey method is used. The sample consists of 176 Chilean consumers who have made at least one purchase online. The data is analysed using structural equation modelling technique (SEM). Findings: The analysis revealed that of the perceived risk and trust factors examined, trust in third party assurances and a cultural environment of trust had the strongest positive influence on intentions to continuing purchasing online. Perceived risk had an inverse relationship with attitude and consumers’ attitude has a positive influence on intentions to purchase online. Trust in online vendors and a propensity to trust were both insignificant. Practical implications: Practically, these results identity which risk and trust beliefs towards purchasing online have the most effect thereby providing insights into how companies should seek to mitigate perceptions of risk to encourage new and return purchasers. Additionally, this research shows that consumers in a Latin American country, recognised as a collectivist, high risk avoidance culture, are willing to make purchases online despite the risks involved. Originality/value: The study and its results is one of few available that consider a Latin American context. The value of the findings provides insights into the specific risk and trust factors that influence Chilean consumers when considering purchasing online. The tested model adds value not only to the literature on Latin American consumer behaviour but also provides guidance for companies offering online retailing facilities in these less developed countries.

Action research as foresight methodology

To the action researcher, who laboriously spends his or her hours working within the local contexts of communities or organisations to co-generate meaningful research, and who’s theories are hardened on the anvil of creating meaningful social change; futures studies might seem the discipline the most peripheral to its interests, and the most ill equipped to deal with the local and intimate domain of community existence. To the futurist, who laboriously spends his or her hours understanding the nuances of history and social change, who through persistent work, begins to make sense of the weak signals and the subtle shifts, action research would seem as simply an auxiliary field, inappropriate for understanding the greater scheme. I invite the reader, however, whether they belong to one camp or the other, to let go of their respective disciplinary perspectives, and see both belonging to each other. [Introduction] .

Human seat modelling using inverse dynamic musculoskeletal models

In this work a biomechanical model is used for simulation of muscle forces necessary to maintain the posture in a car seat under different support conditions.

The economics of happiness : a lifetime perspective

The three studies in this thesis focus on happiness and age and seek to contribute to our understanding of happiness change over the lifetime. The first study contributes by offering an explanation for what was evolving to a ‘stylised fact’ in the economics literature, the U-shape of happiness in age. No U-shape is evident if one makes a visual inspection of the age happiness relationship in the German socio-economic panel data, and, it seems counter-intuitive that we just have to wait until we get old to be happy. Eliminating the very young, the very old, and the first timers from the analysis did not explain away regression results supporting the U-shape of happiness in age, but fixed effect analysis did. Analysis revealed found that reverse causality arising from time-invariant individual traits explained the U-shape of happiness in age in the German population, and the results were robust across six econometric methods. Robustness was added to the German fixed effect finding by replicating it with the Australian and the British socio-economic panel data sets. During analysis of the German data an unexpected finding emerged, an exceedingly large negative linear effect of age on happiness in fixed-effect regressions. There is a large self-reported happiness decline by those who remain in the German panel. A similar decline over time was not evident in the Australian or the British data. After testing away age, time and cohort effects, a time-in-panel effect was found. Germans who remain in the panel for longer progressively report lower levels of happiness. Because time-in-panel effects have not been included in happiness regression specifications, our estimates may be biased; perhaps some economics of the happiness studies, that used German panel data, need revisiting. The second study builds upon the fixed-effect finding of the first study and extends our view of lifetime happiness to a cohort little visited by economists, children. Initial analysis extends our view of lifetime happiness beyond adulthood and revealed a happiness decline in adolescent (15 to 23 year-old) Australians that is twice the size of the happiness decline we see in older Australians (75 to 86 yearolds), who we expect to be unhappy due to declining income, failing health and the onset of death. To resolve a difference of opinion in the literature as to whether childhood happiness decreases, increases, or remains flat in age; survey instruments and an Internet-based survey were developed and used to collect data from four hundred 9 to 14 year-old Australian children. Applying the data to a Model of Childhood Happiness revealed that the natural environment life-satisfaction domain factor did not have a significant effect on childhood happiness. However, the children’s school environment and interactions with friends life-satisfaction domain factors explained over half a steep decline in childhood happiness that is three times larger than what we see in older Australians. Adding personality to the model revealed what we expect to see with adults, extraverted children are happier, but unexpectedly, so are conscientious children. With the steep decline in the happiness of young Australians revealed and explanations offered, the third study builds on the time-invariant individual trait finding from the first study by applying the Australian panel data to an Aggregate Model of Average Happiness over the lifetime. The model’s independent variable is the stress that arises from the interaction between personality and the life event shocks that affect individuals and peers throughout their lives. Interestingly, a graphic depiction of the stress in age relationship reveals an inverse U-shape; an inverse U-shape that looks like the opposite of the U-shape of happiness in age we saw in the first study. The stress arising from life event shocks is found to explain much of the change in average happiness over a lifetime. With the policy recommendations of economists potentially invoking unexpected changes in our lives, the ensuing stress and resulting (un)happiness warrant consideration before economists make policy recommendations.

Concealed substance identification using a defocused inverse spatially offset Raman spectrometer

We report an inverse Spatially Offset Raman Spectrometer capable of non-invasively identifying packaged substances from a distance. Usual inverse SORS spectrometer has a non-contact distance that is equivalent to the focal distance of the collection system. In this work we demonstrate the defocused geometry with a modified data analysis method capable of making inverse SORS measurements from a distance greater than the focal distance of the collection lenses. With the defocused geometry we were able to detect acetaminophen, concealed inside a 2 mm thick plastic bottle, at a non-contact distance of 30 cm.

Using BIM for smarter and safer scaffolding and formwork construction: a preliminary methodology

The goal of this research project is to develop specific BIM objects for temporary construction activities which are fully integrated with object design, construction efficiency and safety parameters. Specifically, the project will deliver modularised electronic scaffolding and formwork objects that will allow designers to easily incorporate them into BIM models to facilitate smarter and safer infrastructure and building construction. This research first identified there is currently a distinct lack of BIM objects for temporary construction works resulting in productivity loss during design and construction, and opportunities for improved consideration of safety standards and practices with the design of scaffolding and formwork. This is particularly relevant in Australia, given the “harmonisation” of OHS legislation across all states and territories from 1 January 2012, meaning that enhancements to Queensland practices will have direct application across Australia. Thus, in conjunction with government and industry partners in Queensland, Australia, the research team developed a strategic three-phase research methodology: (1) the preliminary review phase on industrial scaffolding and formwork practices and BIM implementation; (2) the BIM object development phase with specific safety and productivity functions; and (3) the Queensland-wide workshop phase for product dissemination and training. This paper discusses background review findings, details of the developed methodology, and expected research outcomes and their contributions to the Australian construction industry.

Efficient safety information retrieval on construction sites: a preliminary methodology

IT-supported field data management benefits on-site construction management by improving accessibility to the information and promoting efficient communication between project team members. However, most of on-site safety inspections still heavily rely on subjective judgment and manual reporting processes and thus observers’ experiences often determine the quality of risk identification and control. This study aims to develop a methodology to efficiently retrieve safety-related information so that the safety inspectors can easily access to the relevant site safety information for safer decision making. The proposed methodology consists of three stages: (1) development of a comprehensive safety database which contains information of risk factors, accident types, impact of accidents and safety regulations; (2) identification of relationships among different risk factors based on statistical analysis methods; and (3) user-specified information retrieval using data mining techniques for safety management. This paper presents an overall methodology and preliminary results of the first stage research conducted with 101 accident investigation reports.

Reading research methodology and the reading research quarterly : a question of gender

The paper discusses an aspect of reading research methodology as represented by papers published by the Reading Research Quarterly from the beginning of 1989(volume 24, Number 1) to the end of 1993 (volume 28, Number 4). The discussion suggests some points of departure between this research community and an Australian community broadly defined as poststructural. A focus for this investigation is the function of “gender” within the methodological approaches of the two communities. Suggestions are made regarding some potentially productive points of intersection between the work of American and Australian reading researchers.

Integrating driving and traffic simulators to study railway level crossing safety interventions : a methodology

Safety at Railway Level Crossings (RLXs) is an important issue within the Australian transport system. Crashes at RLXs involving road vehicles in Australia are estimated to cost $10 million each year. Such crashes are mainly due to human factors; unintentional errors contribute to 46% of all fatal collisions and are far more common than deliberate violations. This suggests that innovative intervention targeting drivers are particularly promising to improve RLX safety. In recent years there has been a rapid development of a variety of affordable technologies which can be used to increase driver’s risk awareness around crossings. To date, no research has evaluated the potential effects of such technologies at RLXs in terms of safety, traffic and acceptance of the technology. Integrating driving and traffic simulations is a safe and affordable approach for evaluating these effects. This methodology will be implemented in a driving simulator, where we recreated realistic driving scenario with typical road environments and realistic traffic. This paper presents a methodology for evaluating comprehensively potential benefits and negative effects of such interventions: this methodology evaluates driver awareness at RLXs , driver distraction and workload when using the technology . Subjective assessment on perceived usefulness and ease of use of the technology is obtained from standard questionnaires. Driving simulation will provide a model of driving behaviour at RLXs which will be used to estimate the effects of such new technology on a road network featuring RLX for different market penetrations using a traffic simulation. This methodology can assist in evaluating future safety interventions at RLXs.

Methodology to assess safety effects of future Intelligent Transport Systems on railway level crossings

There is consistent evidence showing that driver behaviour contributes to crashes and near miss incidents at railway level crossings (RLXs). The development of emerging Vehicle-to-Vehicle and Vehicle-to-Infrastructure technologies is a highly promising approach to improve RLX safety. To date, research has not evaluated comprehensively the potential effects of such technologies on driving behaviour at RLXs. This paper presents an on-going research programme assessing the impacts of such new technologies on human factors and drivers’ situational awareness at RLX. Additionally, requirements for the design of such promising technologies and ways to display safety information to drivers were systematically reviewed. Finally, a methodology which comprehensively assesses the effects of in-vehicle and road-based interventions warning the driver of incoming trains at RLXs is discussed, with a focus on both benefits and potential negative behavioural adaptations. The methodology is designed for implementation in a driving simulator and covers compliance, control of the vehicle, distraction, mental workload and drivers’ acceptance. This study has the potential to provide a broad understanding of the effects of deploying new in-vehicle and road-based technologies at RLXs and hence inform policy makers on safety improvements planning for RLX.

Efficient safety information retrieval on construction sites : a preliminary methodology

IT-supported field data management benefits on-site construction management by improving accessibility to the information and promoting efficient communication between project team members. However, most of on-site safety inspections still heavily rely on subjective judgment and manual reporting processes and thus observers’ experiences often determine the quality of risk identification and control. This study aims to develop a methodology to efficiently retrieve safety-related information so that the safety inspectors can easily access to the relevant site safety information for safer decision making. The proposed methodology consists of three stages: (1) development of a comprehensive safety database which contains information of risk factors, accident types, impact of accidents and safety regulations; (2) identification of relationships among different risk factors based on statistical analysis methods; and (3) user-specified information retrieval using data mining techniques for safety management. This paper presents an overall methodology and preliminary results of the first stage research conducted with 101 accident investigation reports.

The nurse researcher : an added dimension to qualitative research methodology

Nurse researchers are increasingly adopting qualitative methodologies for research practice and theory development. These approaches to research are, in many cases, more appropriate for the field of nursing inquiry than the previously dominant techno-rational methods. However, there remains the issue of adapting methodologies developed in other academic disciplines to the nursing research context. This paper draws upon my own experience with interpretive research to raise questions about the issue of nursing research within a social science research framework. The paper argues that by integrating the characteristics of nursing practice with the characteristics of research practice, the researcher can develop a 'nursing lens', an approach to qualitative research that brings an added dimension to social science methodologies in the nursing research context. Attention is drawn to the unique nature of the nurse-patient relationship, and the ways in which this aspect of nursing practice can enhance nursing research. Examples are given from interview transcripts to support this position.