A pharmacogenomic evaluation of migraine therapy

Migraine is a common idiopathic primary headache disorder with significant mental, physical and social health implications. Accompanying an intense unilateral pulsating head pain other characteristic migraine symptoms include nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine cases, neurologic disturbances associated with the aura phase. Although selective serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in alleviating migrainous symptoms in < or = 70% of known sufferers, for the remaining 30%, additional migraine abortive medications remain unsuccessful, not tested or yet to be identified. Genetic characterization of the migrainous disorder is making steady progress with an increasing number of genomic susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic susceptibility regions for various migrainous symptoms. In an effort to develop individualized pharmacotherapeutics, the identification of these migraine endophenotypic loci may well be the catalyst needed to aid in this goal. In this review the authors discuss the present treatment of migraine, known genomic susceptibility regions and results from migraine (genetic) association studies. The authors also discuss pharmacogenomic considerations for more individualized migraine prophylactic treatments.

Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases

Background Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. Methods and Results In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases ( P = 0.006) and earlier age of onset ( P = 0.01). The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05). High-density association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4 ). One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node metastases ( P = 0.01) and tumor size ( P = 0.01). Conclusion Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity.

Creative entrepreneurship education for graduate employability in the creative arts

The higher education sector in Australia is under increasing pressure to prove quality and efficacy of education provision, including graduate outcomes. One of the central tasks of higher education has become to prepare nascent professionals as far as possible for initial employment and future working lives beyond this (Boden & Nedeva, 2010). Tertiary educators in the creative arts face significant and distinctive challenges in demonstrating graduate employability, and creative graduates consistently have the poorest outcomes of any subject grouping. In part, this is because the national graduate destinations survey (Graduate Careers Council of Australia, 2012) does not cater to the distinctive ‘portfolio’ nature of creative careers, or take account of the fact that creative careers can take concerted effort over several years to establish (e.g., McCowan & Wyganowska, 2010). However, it is worth asking whether we as tertiary arts educators are doing enough to prepare creative arts students for the world of work, particularly given that the majority of them will be self-employed to some degree (Bureau of Labour Statistics, 2011, Throsby & Zednik, 2010), and will be challenged to build their own careers without recourse to the support of HR departments or intra-firm promotion schemes. It has been demonstrated empirically that career management and creative enterprise skills are among the most important graduate capabilities in determining early creative career success (Bridgstock, 2011), although these skills do not appear in the Learning and Teaching Academic Standards for the Creative and Performing Arts (2010). This paper explores the nature and development of enterprise capabilities for creative arts students (as distinct from students of the business school), examines best practice in the field internationally, and proposes a theoretically-driven creative arts-specific enterprise curriculum model which commences in first year, for demonstrable impact on student enterprise behaviours (such as grant seeking, professional networking and intention to start an enterprise) and employability.

Gender and other determinants of trust and reciprocity in an experimental labour market amongst Chinese students

Due to economic and demographic changes highly educated women play an important role on the Chinese labour market. Gender has been shown to be an important characteristic that influences behaviour in economic experiments, as have, to a lesser degree, academic major, age and income. We provide a study looking at trust and reciprocity and their determinants in a labour market laboratory experiment. Our experimental data is based on two games, the Gift Exchange Game (GEG) and a variant of this game (the Wage Promising Game, WPG) where the employer's wage offer is non-binding and the employer can choose the wage freely after observing the workers effort. We and that women are less trusting and reciprocal than men in the GEG while this cannot be found in the WPG. Letting participants play the GEG and the WPG, allows us to disentangle reciprocal and risk attitudes. While in the employer role, it seems to be that risk attitude is the main factor, this is not confirmed analysing decisions in the worker role.

Contracting for infrastructure projects as credence goods

Large infrastructure projects are a major responsibility of urban and regional governments, who usually lack expertise to fully specify the demanded projects. Contractors, typically experts on such projects due to experience with similar projects elsewhere, advise of the needed design in their bids. Producing the right design is nevertheless costly. We model such infrastructure projects taking into account their credence goods feature and the costly design effort they require and examine the performance of commonly used contracting methods. We show that when building costs are homogeneous and public information, multi-stage competitive bidding involving shortlisting of two contractors and contingent compensation of both contractors on design efforts outperforms sequential search and the traditional Design-and-Build approach. If building costs are private information of the contractors and are revealed to them after design cost is sunk, sequential search may be superior to the other two methods.

Unpacking the venture creation process

This paper investigates the dimensions of time and effort and how these factors impact on the venture creation process in Australia. Findings of interest in this paper include: • First and foremost business planning is used as a thinking tool within the boundaries of the firm. • Business planning is more strongly associated with firms that are more ambitious, being built by teams, draw on more experience or education. • Industry characteristics in part drive the duration required for venture creation. Manufacturing and Agriculture based firms seemingly take longer timeframes than other industries. Extended venture creation times frames are also associated with firms that aim to bring more novel concepts to market.

Sampling environmental acoustic recordings to determine bird species richness

Acoustic sensors can be used to estimate species richness for vocal species such as birds. They can continuously and passively record large volumes of data over extended periods. These data must subsequently be analyzed to detect the presence of vocal species. Automated analysis of acoustic data for large numbers of species is complex and can be subject to high levels of false positive and false negative results. Manual analysis by experienced surveyors can produce accurate results; however the time and effort required to process even small volumes of data can make manual analysis prohibitive. This study examined the use of sampling methods to reduce the cost of analyzing large volumes of acoustic sensor data, while retaining high levels of species detection accuracy. Utilizing five days of manually analyzed acoustic sensor data from four sites, we examined a range of sampling frequencies and methods including random, stratified, and biologically informed. We found that randomly selecting 120 one-minute samples from the three hours immediately following dawn over five days of recordings, detected the highest number of species. On average, this method detected 62% of total species from 120 one-minute samples, compared to 34% of total species detected from traditional area search methods. Our results demonstrate that targeted sampling methods can provide an effective means for analyzing large volumes of acoustic sensor data efficiently and accurately. Development of automated and semi-automated techniques is required to assist in analyzing large volumes of acoustic sensor data. Read More: http://www.esajournals.org/doi/abs/10.1890/12-2088.1

A framework for cost-aware process management : cost reporting and cost prediction

Organisations are constantly seeking efficiency gains for their business processes in terms of time and cost. Management accounting enables detailed cost reporting of business operations for decision making purposes, although significant effort is required to gather accurate operational data. Process mining, on the other hand, may provide valuable insight into processes through analysis of events recorded in logs by IT systems, but its primary focus is not on cost implications. In this paper, a framework is proposed which aims to exploit the strengths of both fields in order to better support management decisions on cost control. This is achieved by automatically merging cost data with historical data from event logs for the purposes of monitoring, predicting, and reporting process-related costs. The on-demand generation of accurate, relevant and timely cost reports, in a style akin to reports in the area of management accounting, will also be illustrated. This is achieved through extending the open-source process mining framework ProM.

Understanding the actualization of affordances: A study in the process modeling context

The affordances concept describes the possibilities for goal-oriented action that technical objects offer to specified users. This notion has received growing attention from IS researchers. However, few studies have gone beyond contextualizing parts of the concept to a specific setting – the tip of the iceberg. In this research-in-progress paper, we report on our efforts to further develop the IS discipline’s understanding of affordances from informational objects. Specifically, we seek to extend extant theory on the origin and actualization of affordances. We develop a model that describes the process by which affordances are perceived and actualized and their dependence on information and actualization effort. We illustrate our emergent theory in the context of conceptual process models used by analysts for purposes of information systems analysis and design. We offer suggestions for operationalizing and testing this model empirically, and provide details about our design of a mixed-methods study currently in progress.

Transitioning from dependent to more independent learners : Using video tutorials as a means of helping students help themselves

This paper examines the use of short video tutorials in a post-graduate accounting subject, as a means of helping students transition from dependent to more independent learners. Five short (three to five minute) video tutorials were introduced in an effort to shift the reliance for learning from the lecturer to the student. Students’ usage of video tutorials, comments by students, and reliance on teaching staff for individual assistance were monitored over three semesters from 2008 to 2009. Interviews with students were then conducted in late 2009 to more comprehensively evaluate the use and benefits of video tutorials. Findings reveal preliminary but positive outcomes in terms of both more efficient teaching and more effective learning.

Modelling busway station dwell time using smart cards

Dwell time at the busway station has a significant effect on bus capacity and delay. Dwell time has conventionally been estimated using models developed on the basis of field survey data. However field survey is resource and cost intensive, so dwell time estimation based on limited observations can be somewhat inaccurate. Most public transport systems are now equipped with Automatic Passenger Count (APC) and/or Automatic Fare Collection (AFC) systems. AFC in particular reduces on-board ticketing time, driver’s work load and ultimately reduces bus dwell time. AFC systems can record all passenger transactions providing transit agencies with access to vast quantities of data. AFC data provides transaction timestamps, however this information differs from dwell time because passengers may tag on or tag off at times other than when doors open and close. This research effort contended that models could be developed to reliably estimate dwell time distributions when measured distributions of transaction times are known. Development of the models required calibration and validation using field survey data of actual dwell times, and an appreciation of another component of transaction time being bus time in queue. This research develops models for a peak period and off peak period at a busway station on the South East Busway (SEB) in Brisbane, Australia.

A systematic approach for selecting lean strategies and assessing leanness in manufacturing organizations

Lean strategies have been developed to eliminate or reduce manufacturing waste and thus improve operational efficiency in manufacturing processes. However, implementing lean strategies requires a large amount of resources and, in practice, manufacturers encounter difficulties in selecting appropriate lean strategies within their resource constraints. There is currently no systematic methodology available for selecting appropriate lean strategies within a manufacturer's resource constraints. In the lean transformation process, it is also critical to measure the current and desired leanness levels in order to clearly evaluate lean implementation efforts. Despite the fact that many lean strategies are utilized to reduce or eliminate manufacturing waste, little effort has been directed towards properly assessing the leanness of manufacturing organizations. In practice, a single or specific group of metrics (either qualitative or quantitative) will only partially measure the overall leanness. Existing leanness assessment methodologies do not offer a comprehensive evaluation method, integrating both quantitative and qualitative lean measures into a single quantitative value for measuring the overall leanness of an organization. This research aims to develop mathematical models and a systematic methodology for selecting appropriate lean strategies and evaluating the leanness levels in manufacturing organizations. Mathematical models were formulated and a methodology was developed for selecting appropriate lean strategies within manufacturers' limited amount of available resources to reduce their identified wastes. A leanness assessment model was developed by using the fuzzy concept to assess the leanness level and to recommend an optimum leanness value for a manufacturing organization. In the proposed leanness assessment model, both quantitative and qualitative input factors have been taken into account. Based on program developed in MATLAB and C#, a decision support tool (DST) was developed for decision makers to select lean strategies and evaluate the leanness value based on the proposed models and methodology hence sustain the lean implementation efforts. A case study was conducted to demonstrate the effectiveness of these proposed models and methodology. Case study results suggested that out of 10 wastes identified, the case organization (ABC Limited) is able to improve a maximum of six wastes from the selected workstation within their resource limitations. The selected wastes are: unnecessary motion, setup time, unnecessary transportation, inappropriate processing, work in process and raw material inventory and suggested lean strategies are: 5S, Just-In-Time, Kanban System, the Visual Management System (VMS), Cellular Manufacturing, Standard Work Process using method-time measurement (MTM), and Single Minute Exchange of Die (SMED). From the suggested lean strategies, the impact of 5S was demonstrated by measuring the leanness level of two different situations in ABC. After that, MTM was suggested as a standard work process for further improvement of the current leanness value. The initial status of the organization showed a leanness value of 0.12. By applying 5S, the leanness level significantly improved to reach 0.19 and the simulation of MTM as a standard work method shows the leanness value could be improved to 0.31. The optimum leanness value of ABC was calculated to be 0.64. These leanness values provided a quantitative indication of the impacts of improvement initiatives in terms of the overall leanness level to the case organization. Sensitivity analsysis and a t-test were also performed to validate the model proposed. This research advances the current knowledge base by developing mathematical models and methodologies to overcome lean strategy selection and leanness assessment problems. By selecting appropriate lean strategies, a manufacturer can better prioritize implementation efforts and resources to maximize the benefits of implementing lean strategies in their organization. The leanness index is used to evaluate an organization's current (before lean implementation) leanness state against the state after lean implementation and to establish benchmarking (the optimum leanness state). Hence, this research provides a continuous improvement tool for a lean manufacturing organization.

Beyond normal competencies : understanding organisation designs to develop and sustain IT-related capabilities

It is apparent that IT resources are important for organisations. It is also clear that organisations unique competencies, their IT-related capabilities, leverage the IT resources uniquely to create and sustain competitive advantage. However, IT resources are dynamic, and evolve at an exponential rate. This means that organisations will need to sustain their competencies to leverage opportunities offered by new IT resources. Research on ways to sustain IT-related capabilities is limited and a deeper understanding of this situation is important. Amongst other factors, a possible reason for this lack of progress in this area could be due to the lack of validated measurement items of the theoretical constructs to conduct such studies. We suggest an environment in which organisations could build new and sustain their existing IT-related capabilities. We then report on the development of valid and reliable measures for this environment. The validated measures would be useful in extending our understanding on how firms could sustain their IT-related capabilities. This effort will provide a deeper understanding of how firms can secure sustainable IT-related business value from their acquired IT resources.

Natural, engineered and synthetic inhibitors of kallikrein-related peptidases

There is a rapidly growing appreciation of the important physiological roles played by kallikreins and kallikrein-related peptidases (KLKs). Recent studies have revealed that these enzymes control key events in processes as diverse as inflammation and skin desquamation. Accordingly, there is considerable interest in developing tools to further dissect kallikrein activity, and a burgeoning effort aimed at producing lead inhibitors for therapeutic development. Indeed, several candidate inhibitors are already in clinical trials. This chapter surveys the naturally occurring kallikrein inhibitors, together with strategies for employing these molecules as bioscaffolds, as well as current progress in the development of small-molecule kallikrein inhibitors.

Moderate sleep restriction in treated older male OSA participants: Greater impairment during monotonous driving compared with controls

Objectives To examine the effects on monotonous driving of normal sleep versus one night of sleep restriction in continuous positive airway pressure (CPAP) treated obstructive sleep apnoea (OSA) patients compared with age matched healthy controls. Methods Nineteen CPAP treated compliant male OSA patients (OSA-treated patients (OPs)), aged 50–75 years, and 20 healthy age-matched controls underwent both a normal night’s sleep and sleep restriction to 5 h (OPs remained on CPAP) in a counterbalanced design. All participants completed a 2 h afternoon monotonous drive in a realistic car simulator. Driving was monitored for sleepiness-related minor and major lane deviations, with ‘safe’ driving time being total time driven prior to first major lane deviation. EEGs were recorded continuously, and subjective sleepiness ratings were taken at regular intervals throughout the drive. Results After a normal night’s sleep, OPs and controls did not differ in terms of driving performance or in their ability to assess the levels of their own sleepiness, with both groups driving ‘safely’ for approximately 90 min. However, after sleep restriction, OPs had a significantly shorter (65 min) safe driving time and had to apply more compensatory effort to maintain their alertness compared with controls. They also underestimated the enhanced sleepiness. Nevertheless, apart from this caveat, there were generally close associations between subjective sleepiness, likelihood of a major lane deviation and EEG changes indicative of sleepiness. Conclusions With a normal night’s sleep, effectively treated older men with OSA drive as safely as healthy men of the same age. However, after restricted sleep, driving impairment is worse than that of controls. This suggests that, although successful CPAP treatment can alleviate potential detrimental effects of OSA on monotonous driving following normal sleep, these patients remain more vulnerable to sleep restriction.