Negotiation 2.0 in the twitter age : using Web 2.0 applications to facilitate successful negotiation outcomes

The high-pressure, cross-cultural, cross-factional and frequently cross-national nature of contemporary negotiation means that there are a number of clements potentially hampering efforts to achieve successful negotiation outcomes from face-to-face interactions. These hindrances include: resource scarcity (for example, finances, technology and facilities), time scarcity, geographical separation, lack of a COnl1110n language and an inability to Inaintain a consistent ongoing dialogue.

Domestic and international innovation partnerships : do they matter for innovation outcomes of South African firms?

This paper studies the impact of the diversity of domestic and international innovation partnerships on the innovation outcomes of South African firms. A number of competing hypotheses are formulated and tested empirically using a sample of South African firms in manufacturing and services by applying Ordinary Least Squares regression analyses. Results show that having an innovation partnership, particularly an international partnership, is beneficial to innovation outcomes. However, it also emerges that too diverse a set of international partnerships is detrimental to innovation outcomes. The paper concludes with a discussion and a number of proposals for future research.

Defences in medical negligence : to what extent has tort law reform in Australia limited the liability of health professionals?

Tort law reform has resulted in legislation being passed by all Australian jurisdictions in the past decade implementing the recommendations contained in the Ipp Report. The report was in response to a perceived crisis in medical indemnity insurance. The objective was to restrict and limit liability in negligence actions. This paper will consider to what extent the reforms have impacted on the liability of health professionals in medical negligence actions. After an analysis of the legislation, it will be argued in this paper that while there has been some limitation and restriction, courts have generally interpreted the civil liability reforms in compliance with the common law. It has been the impact of statutory limits on the assessment of damages through thresholds and caps which has limited the liability of health professionals in medical negligence actions.

A brief history of haemotopoietic stem cell Ex vivo expansion

Haematopoiesis is the process by which a hierarchy of mature and progenitor blood cells are formed. These cell populations are all derived from multipotent haematopoietic stem cells (HSC), which reside in the bone marrow ‘niche’ of adult humans. Over the lifetime of a healthy individual, this HSC population replenishes between 1010-1011 blood cells on a daily basis. Dysregulation of this system can lead to a number of haematopoietic diseases, including aplastic anaemias and leukaemias, which result in, or require for disease resolution, bone marrow cell depletion. In 1956, E. Donnall Thomas demonstrated that haematopoiesis could be restored by transplanting bone marrow-derived cells from one man into his identical twin brother, who was suffering from advanced leukaemia. His success drew significant interest in academic research and medicine communities, and 12 years later, the first successful allogeneic transplant was performed. To this day, HSCs remain the most studied and characterised stem cell population. In fact, HSCs are the only stem cell population routinely utilised in the clinic. As such, HSCs function as a model system both for the biological investigation of stem cells, as well as for their clinical application. Herein, we briefly review HSC transplantation, strategies for the ex vivo cultivation of HSCs, recent clinical outcomes, and their impact on the future direction of HSC transplantation therapy.

Applications of medical image processing in the diagnosis and treatment of spinal deformity

In Chapter 10, Adam and Dougherty describe the application of medical image processing to the assessment and treatment of spinal deformity, with a focus on the surgical treatment of idiopathic scoliosis. The natural history of spinal deformity and current approaches to surgical and non-surgical treatment are briefly described, followed by an overview of current clinically used imaging modalities. The key metrics currently used to assess the severity and progression of spinal deformities from medical images are presented, followed by a discussion of the errors and uncertainties involved in manual measurements. This provides the context for an analysis of automated and semi-automated image processing approaches to measure spinal curve shape and severity in two and three dimensions.

Bayesian mixtures for modelling complex medical data : a case study in Parkinson’s disease

Mixture models are a flexible tool for unsupervised clustering that have found popularity in a vast array of research areas. In studies of medicine, the use of mixtures holds the potential to greatly enhance our understanding of patient responses through the identification of clinically meaningful clusters that, given the complexity of many data sources, may otherwise by intangible. Furthermore, when developed in the Bayesian framework, mixture models provide a natural means for capturing and propagating uncertainty in different aspects of a clustering solution, arguably resulting in richer analyses of the population under study. This thesis aims to investigate the use of Bayesian mixture models in analysing varied and detailed sources of patient information collected in the study of complex disease. The first aim of this thesis is to showcase the flexibility of mixture models in modelling markedly different types of data. In particular, we examine three common variants on the mixture model, namely, finite mixtures, Dirichlet Process mixtures and hidden Markov models. Beyond the development and application of these models to different sources of data, this thesis also focuses on modelling different aspects relating to uncertainty in clustering. Examples of clustering uncertainty considered are uncertainty in a patient’s true cluster membership and accounting for uncertainty in the true number of clusters present. Finally, this thesis aims to address and propose solutions to the task of comparing clustering solutions, whether this be comparing patients or observations assigned to different subgroups or comparing clustering solutions over multiple datasets. To address these aims, we consider a case study in Parkinson’s disease (PD), a complex and commonly diagnosed neurodegenerative disorder. In particular, two commonly collected sources of patient information are considered. The first source of data are on symptoms associated with PD, recorded using the Unified Parkinson’s Disease Rating Scale (UPDRS) and constitutes the first half of this thesis. The second half of this thesis is dedicated to the analysis of microelectrode recordings collected during Deep Brain Stimulation (DBS), a popular palliative treatment for advanced PD. Analysis of this second source of data centers on the problems of unsupervised detection and sorting of action potentials or "spikes" in recordings of multiple cell activity, providing valuable information on real time neural activity in the brain.

Smart Measures for Sustainable Outcomes: Integrated Considerations for Sustainable Refurbishment of Office Buildings

The increasing stock of aging office buildings will see a significant growth in retrofitting projects in Australian capital cities. Stakeholders of refitting works will also need to take on the sustainability challenge and realize tangible outcomes through project delivery. Traditionally, decision making for aged buildings, when facing the alternatives, is typically economically driven and on ad hoc basis. This leads to the tendency to either delay refitting for as long as possible thus causing building conditions to deteriorate, or simply demolish and rebuild with unjust financial burden. The technologies involved are often limited to typical strip-clean and repartition with dry walls and office cubicles. Changing business operational patterns, the efficiency of office space, and the demand on improved workplace environment, will need more innovative and intelligent approaches to refurbishing office buildings. For example, such projects may need to respond to political, social, environmental and financial implications. There is a need for the total consideration of buildings structural assessment, modeling of operating and maintenance costs, new architectural and engineering designs that maximise the utility of the existing structure and resulting productivity improvement, specific construction management procedures including procurement methods, work flow and scheduling and occupational health and safety. Recycling potential and conformance to codes may be other major issues. This paper introduces examples of Australian research projects which provided a more holistic approach to the decision making of refurbishing office space, using appropriate building technologies and products, assessment of residual service life, floor space optimisation and project procurement in order to bring about sustainable outcomes. The paper also discusses a specific case study on critical factors that influence key building components for these projects and issues for integrated decision support when dealing with the refurbishment, and indeed the “re-life”, of office buildings.

Towards semantic search and inference in electronic medical records : an approach using concept-based information retrieval

For more than a decade research in the field of context aware computing has aimed to find ways to exploit situational information that can be detected by mobile computing and sensor technologies. The goal is to provide people with new and improved applications, enhanced functionality and better use experience (Dey, 2001). Early applications focused on representing or computing on physical parameters, such as showing your location and the location of people or things around you. Such applications might show where the next bus is, which of your friends is in the vicinity and so on. With the advent of social networking software and microblogging sites such as Facebook and Twitter, recommender systems and so on context-aware computing is moving towards mining the social web in order to provide better representations and understanding of context, including social context. In this paper we begin by recapping different theoretical framings of context. We then discuss the problem of context- aware computing from a design perspective.

Gender and new venture outcomes : not better or worse, just different

We investigate how differences in the goals of male and female entrepreneurs affect business resources, outcomes and satisfaction with those outcomes. To investigate this topic we use the CAUSEE database to access a longitudinal sample of 247 female-controlled and 332 male-controlled young Australian firms. We find that female entrepreneurs are less motivated by business growth, invest less time developing their businesses and yet even when profits are lower they are more satisfied with their profit performance. Our results support prior qualitative studies indicating that female business owners want greater flexibility and manageability in terms of balancing their family and work responsibilities. Our findings also suggest that future dialogue on firm performance should include an analysis of the entrepreneur’s achievement in terms of both financial and personal goals.

The role of insulin and IGF2 signalling on metabolic pathways in prostate cancer progression

Prostate cancer (CaP) is the most commonly diagnosed cancer in males in Australia, North America, and Europe. If found early and locally confined, CaP can be treated with radical prostatectomy or radiation therapy; however, 25-40% patients will relapse and go on to advanced disease. The most common therapy in these cases is androgen deprivation therapy (ADT), which suppresses androgen production from the testis. Lack of the testicular androgen supply causes cells of the prostate to undergo apoptosis. However, in some cases the regression initially seen with ADT eventually gives way to a growth of a population of cancerous cells that no longer require testicular androgens. This phenotype is essentially fatal and is termed castrate resistant prostate cancer (CRPC). In addition to eventual regression, there are many undesirable side effects which accompany ADT, including development of a metabolic syndrome, which is defined by the U.S. National Library of Medicine as “a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.” This project will focus on the effect of ADT induced hyperinsulinemia, as mimicked by treating androgen receptor positive CaP cells with insulin in a serum (hormone) deprived environment. While this side effect is not widely explored, in this thesis it is demonstrated for the first time that insulin upregulates pathways important to CaP progression. Our group has previously shown that during CaP progression, the enzymes necessary for de novo steroidogenesis are upregulated in the LNCaP xenograft model, total steroid levels are increased in tumours compared to pre castrate levels, and de novo steroidogenesis from radio-labelled acetate has been demonstrated. Because of the CaP dependence on AR for survival, we and other groups believe that CaP cells carry out de novo steroidogenesis to survive in androgen deprived conditions. Because (a) men on ADT often develop metabolic syndrome, and (b) men with lifestyle-induced obesity and hyperinsulinemia have worse prognosis and faster disease progression, and because (c) insulin causes steroidogenesis in other cell lines, the hypothesis that insulin may contribute to CaP progression through upregulation of steroidogenesis was explored. Insulin upregulates steroidogenesis enzymes at the mRNA level in three AR positive cell lines, as well as upregulating these enzymes at the protein level in two cell lines. It has also been demonstrated that insulin increases mitochondrial (functional) levels of steroid acute regulatory protein (StAR). Furthermore, insulin causes increased levels of total steroids in and induction of de novo steroid synthesis by insulin has been demonstrated at levels induced sufficient to activate AR. The effect of insulin analogs on CaP steroidogenesis in LNCaP and VCaP cells has also been investigated because epidemiological studies suggest that some of the analogs developed may have more cancer stimulatory effects than normal insulin. In this project, despite the signalling differences between glargine, X10, and insulin, these analogs did not appear to induce steroidogenesis any more potently that normal insulin. The effect of insulin of MCF7breast cancer cells was also investigated with results suggesting that breast cancer cells may be capable of de novo steroidogenesis, and that increase in estradiol production may be exacerbated by insulin. Insulin has also been long known to stimulate lipogenesis in the liver and adipocytes, and has been demonstrated to increase lipogenesis in breast cancer cells; therefore, investigation of the effect of insulin on lipogenesis, which is a hallmark of aggressive cancers, was investigated. In CaP progression sterol regulatory element binding protein (SREBP) is dysregulated and upregulates fatty acid synthase (FASN), acetyl CoA-carboxylase, and other lipogenesis genes. SREBP is important for steroidogenesis and in this project has been shown to be upregulated by insulin in CaP cells. Fatty acid synthesis provides building blocks of membrane growth, provides substrates for acid oxidation, the main energy source for CaP cells, provides building blocks for anti-apoptotic and proinflammatory molecules, and provides molecules that stimulate steroidogenesis. In this project it has been shown that insulin upregulates FASN and ACC, which synthesize fatty acids, as well as upregulating hormone sensitive lipase (HSL), diazepam-binding inhibitor (DBI), and long-chain acyl-CoA synthetase 3 (ACSL3), which contribute to lipid activation of steroidogenesis. Insulin also upregulates total lipid levels and de novo lipogenesis, which can be suppressed by inhibition of the insulin receptor (INSR). The fatty acids synthesized after insulin treatment are those that have been associated with CaP; furthermore, microarray data suggests insulin may upregulate fatty acid biosynthesis, metabolism and arachidonic acid metabolism pathways, which have been implicated in CaP growth and survival. Pharmacological agents used to treat patients with hyperinsulinemia/ hyperlipidemia have gained much interest in regards to CaP risk and treatment; however, the scientific rationale behind these clinical applications has not been examined. This thesis explores whether the use of metformin or simvastatin would decrease either lipogenesis or steroidogenesis or both in CaP cells. Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, which blocks synthesis of cholesterol, the building block of steroids/ androgens. It has also been postulated to down regulate SREBP in other metabolic disorders. It has been shown in this thesis, in LNCaP cells, that simvastatin inhibited and decreased insulin induced steroidogenesis and lipogenesis, respectively, but increased these pathways in the absence of insulin. Conversely, metformin, which activates AMP-activated protein kinase (AMPK) to shut down lipogenesis, cholesterol synthesis, and protein synthesis, highly suppresses both steroidogenesis and lipogenesis in the presence and absence of insulin. Lastly, because it has been demonstrated to increase steroidogenesis in other cell lines, and because the elucidation of any factors affecting steroidogenesis is important to understanding CaP, the effect of IGF2 on steroidogenesis in CaP cells was investigated. In patient samples, as men progress to CRPC, IGF2 mRNA and the protein levels of the receptors it may signal through are upregulated. It has also been demonstrated that IGF2 upregulates steroidogenic enzymes at both the mRNA and protein levels in LNCaP cells, increases intracellular and secreted steroid/androgen levels in LNCaPs to levels sufficient to stimulate the AR, and upregulated de novo steroidogenesis in LNCaPs and VCaPs. As well, inhibition of INSR and insulin-like growth factor 1 receptor (IGF1R), which IGF2 signals through, suggests that induction of steroidogenesis may be occurring predominantly through IGF1R. In summary, this project has illuminated for the first time that insulin is likely to play a large role in cancer progression, through upregulation of the steroidogenesis and lipogenesis pathways at the mRNA and protein levels, and production levels, and demonstrates a novel role for IGF-II in CaP progression through stimulation of steroidogenesis. It has also been demonstrated that metformin and simvastatin drugs may be useful in suppressing the insulin induction of these pathways. This project affirms the pathways by which ADT- induced metabolic syndrome may exacerbate CaP progression and strongly suggests that the monitoring and modulation of the metabolic state of CaP patients could have a strong impact on their therapeutic outcomes.

Application of Geographic Modeling Techniques to Quantify Spatial Access to Health Services Before and After an Acute Cardiac Event: The Cardiac ARIA Project

Background: Access to cardiac services is essential for appropriate implementation of evidence-based therapies to improve outcomes. The Cardiac Accessibility and Remoteness Index for Australia (Cardiac ARIA) aimed to derive an objective, geographic measure reflecting access to cardiac services. Methods: An expert panel defined an evidence-based clinical pathway. Using Geographic Information Systems (GIS), a numeric/alpha index was developed at two points along the continuum of care. The acute category (numeric) measured the time from the emergency call to arrival at an appropriate medical facility via road ambulance. The aftercare category (alpha) measured access to four basic services (family doctor, pharmacy, cardiac rehabilitation, and pathology services) when a patient returned to their community. Results: The numeric index ranged from 1 (access to principle referral center with cardiac catheterization service ≤ 1 hour) to 8 (no ambulance service, > 3 hours to medical facility, air transport required). The alphabetic index ranged from A (all 4 services available within 1 hour drive-time) to E (no services available within 1 hour). 13.9 million (71%) Australians resided within Cardiac ARIA 1A locations (hospital with cardiac catheterization laboratory and all aftercare within 1 hour). Those outside Cardiac 1A were over-represented by people aged over 65 years (32%) and Indigenous people (60%). Conclusion: The Cardiac ARIA index demonstrated substantial inequity in access to cardiac services in Australia. This methodology can be used to inform cardiology health service planning and the methodology could be applied to other common disease states within other regions of the world.

Overlapping medical alarms are almost indiscriminable

Objective: We explore how accurately and quickly nurses can identify melodic medical equipment alarms when no mnemonics are used, when alarms may overlap, and when concurrent tasks are performed. Background: The international standard IEC 60601-1-8 (International Electrotechnical Commission, 2005) has proposed simple melodies to distinguish seven alarm sources. Previous studies with nonmedical participants reveal poor learning of melodic alarms and persistent confusions between some of them. The effects of domain expertise, concurrent tasks, and alarm overlaps are unknown. Method: Fourteen intensive care and general medical unit nurses learned the melodic alarms without mnemonics in two sessions on separate days. In the second half of Day 2 the nurses identified single alarms or pairs of alarms played in sequential, partially overlapping, or nearly completely overlapping configurations. For half the experimental blocks nurses performed a concurrent mental arithmetic task. Results: Nurses' learning was poor and was no better than the learning of nonnurses in a previous study. Nurses showed the previously noted confusions between alarms. Overlapping alarms were exceptionally difficult to identify. The concurrent task affected response time but not accuracy. Conclusion: Because of a failure of auditory stream segregation, the melodic alarms cannot be discriminated when they overlap. Directives to sequence the sounding of alarms in medical electrical equipment must be strictly adhered to, or the alarms must redesigned to support better auditory streaming. Application: Actual or potential uses of this research include the implementation of IEC 60601-1-8 alarms in medical electrical equipment.

Learnability and discriminability of melodic medical equipment alarms

Melodic alarms proposed in the IEC 60601-1-8 standard for medical electrical equipment were tested for learnability and discriminability. Thirty-three non-anaesthetist participants learned the alarms over two sessions of practice, with or without mnemonics suggested in the standard. Fewer than 30% of participants could identify the alarms with 100% accuracy at the end of practice. Confusions persisted between pairs of alarms, especially if mnemonics were used during learning (p = 0.011). Participants responded faster (p < 0.00001) and more accurately (p = 0.002) to medium priority alarms than to high priority alarms, even though they rated the high priority alarms as sounding more urgent (p < 0.00001). Participants with at least 1 year of formal musical training identified the alarms more accurately (p = 0.0002) than musically untrained participants, and found the task easier overall (p < 0.00001). More intensive studies of the IEC 60601-1-8 alarms are needed for their effectiveness to be determined.