Virtual Clinical Trials in PET Imaging for Improved Diagnosis of and Evaluation of Therapies for Cancer

Thesis (Ph.D.)--University of Washington, 2016-08

Uncertainty Management in Acquisitions: What Scenario Analysis Could Offer

This study answers to How scenario analysis could help acquiring companies to reduce uncertainty in the acquisition process? It is due to the mismatch between academic world’s caveat emptor and business world’s eagerness to pursue acquisitions that motivated this study. Acquisitions are as popular as ever, thus, managing the uncertainty surrounding these transactions is relevant. This study creates a generic theoretical model with a strategy-level scope. Thus, the study does not discuss nor does it seek answers to operational issues related in both fields. This study is explorative and constructivist in nature. It discusses briefly the concepts and relatedness of risk and uncertainty and establishes a hierarchy between these two: Risks being a “sub-section” of uncertainty, although not with clear boundaries. Acquisition theory follows the process view that understands acquisitions as a process with various levels – some strategic, some operational. Scenario analysis is presented as tool for management to enrich their strategic discussion and understand their future options. The empirical data collection is done through interviewing. The results are reflected on literature on strategic management, scenario literature, and on a consultancy’s report picturing firm’s strategies in accordance with their acquisition processes. The study has an abductive approach as it tries to combine multiple views and generates discussion between literature review, interviews, the report, and second round of literature. The model suggests three propositions: First, at the strategic decision making level, when the decision whether or not to pursue an acquisition growth strategy has been made, it provides firms new data and enriches the strategic discussion. Second, when the acquisition strategy has been created, it can be applied as a tool to measure possible acquisition targets against the backdrop of the first set of scenarios. Third, due to the scenario analysis’ requirement to include people with various backgrounds and from multiple levels of the corporate hierarchy, it could help managers to avoid biases stemming from hubris.

Management interventions in dairy herds: exploring within herd uncertainty using an integrated Bayesian model

Knowledge of the efficacy of an intervention for disease control on an individual farm is essential to make good decisions on preventive healthcare, but the uncertainty in outcome associated with undertaking a specific control strategy has rarely been considered in veterinary medicine. The purpose of this research was to explore the uncertainty in change in disease incidence and financial benefit that could occur on different farms, when two effective farm management interventions are undertaken. Bovine mastitis was used as an example disease and the research was conducted using data from an intervention study as prior information within an integrated Bayesian simulation model. Predictions were made of the reduction in clinical mastitis within 30 days of calving on 52 farms, attributable to the application of two herd interventions previously reported as effective; rotation of dry cow pasture and differential dry cow therapy. Results indicated that there were important degrees of uncertainty in the predicted reduction in clinical mastitis for individual farms when either intervention was undertaken; the magnitude of the 95% credible intervals for reduced clinical mastitis incidence were substantial and of clinical relevance. The large uncertainty associated with the predicted reduction in clinical mastitis attributable to the interventions resulted in important variability in possible financial outcomes for each farm. The uncertainty in outcome associated with farm control measures illustrates the difficulty facing a veterinary clinician when making an on-farm decision and highlights the importance of iterative herd health procedures (continual evaluation, reassessment and adjusted interventions) to optimise health in an individual herd.

Investment decision-making under risk (reliability) and uncertainty for infrastructure asset management

Risks and uncertainties are inevitable in engineering projects and infrastructure investments. Decisions about investment in infrastructure such as for maintenance, rehabilitation and construction works can pose risks, and may generate significant impacts on social, cultural, environmental and other related issues. This report presents the results of a literature review of current practice in identifying, quantifying and managing risks and predicting impacts as part of the planning and assessment process for infrastructure investment proposals. In assessing proposals for investment in infrastructure, it is necessary to consider social, cultural and environmental risks and impacts to the overall community, as well as financial risks to the investor. The report defines and explains the concept of risk and uncertainty, and describes the three main methodology approaches to the analysis of risk and uncertainty in investment planning for infrastructure, viz examining a range of scenarios or options, sensitivity analysis, and a statistical probability approach, listed here in order of increasing merit and complexity. Forecasts of costs, benefits and community impacts of infrastructure are recognised as central aspects of developing and assessing investment proposals. Increasingly complex modelling techniques are being used for investment evaluation. The literature review identified forecasting errors as the major cause of risk. The report contains a summary of the broad nature of decision-making tools used by governments and other organisations in Australia, New Zealand, Europe and North America, and shows their overall approach to risk assessment in assessing public infrastructure proposals. While there are established techniques to quantify financial and economic risks, quantification is far less developed for political, social and environmental risks and impacts. The report contains a summary of the broad nature of decision-making tools used by governments and other organisations in Australia, New Zealand, Europe and North America, and shows their overall approach to risk assessment in assessing public infrastructure proposals. While there are established techniques to quantify financial and economic risks, quantification is far less developed for political, social and environmental risks and impacts. For risks that cannot be readily quantified, assessment techniques commonly include classification or rating systems for likelihood and consequence. The report outlines the system used by the Australian Defence Organisation and in the Australian Standard on risk management. After each risk is identified and quantified or rated, consideration can be given to reducing the risk, and managing any remaining risk as part of the scope of the project. The literature review identified use of risk mapping techniques by a North American chemical company and by the Australian Defence Organisation. This literature review has enabled a risk assessment strategy to be developed, and will underpin an examination of the feasibility of developing a risk assessment capability using a probability approach.

Classifying an opponent’s behaviour in robot soccer

This paper illustrates the prediction of opponent behaviour in a competitive, highly dynamic, multi-agent and partially observable environment, namely RoboCup small size league robot soccer. The performance is illustrated in the context of the highly successful robot soccer team, the RoboRoos. The project is broken into three tasks; classification of behaviours, modelling and prediction of behaviours and integration of the predictions into the existing planning system. A probabilistic approach is taken to dealing with the uncertainty in the observations and with representing the uncertainty in the prediction of the behaviours. Results are shown for a classification system using a Naïve Bayesian Network that determines the opponent’s current behaviour. These results are compared to an expert designed fuzzy behaviour classification system. The paper illustrates how the modelling system will use the information from behaviour classification to produce probability distributions that model the manner with which the opponents perform their behaviours. These probability distributions are show to match well with the existing multi-agent planning system (MAPS) that forms the core of the RoboRoos system.

Resilience in critical infrastructures : the case of the Queensland electricity industry

The reliability of Critical Infrastructure is considered to be a fundamental expectation of modern societies. These large-scale socio-technical systems have always, due to their complex nature, been faced with threats challenging their ongoing functioning. However, increasing uncertainty in addition to the trend of infrastructure fragmentation has made reliable service provision not only a key organisational goal, but a major continuity challenge: especially given the highly interdependent network conditions that exist both regionally and globally. The notion of resilience as an adaptive capacity supporting infrastructure reliability under conditions of uncertainty and change has emerged as a critical capacity for systems of infrastructure and the organisations responsible for their reliable management. This study explores infrastructure reliability through the lens of resilience from an organisation and system perspective using two recognised resilience-enhancing management practices, High Reliability Theory (HRT) and Business Continuity Management (BCM) to better understand how this phenomenon manifests within a partially fragmented (corporatised) critical infrastructure industry – The Queensland Electricity Industry. The methodological approach involved a single case study design (industry) with embedded sub-units of analysis (organisations), utilising in-depth interviews and document analysis to illicit findings. Derived from detailed assessment of BCM and Reliability-Enhancing characteristics, findings suggest that the industry as a whole exhibits resilient functioning, however this was found to manifest at different levels across the industry and in different combinations. Whilst there were distinct differences in respect to resilient capabilities at the organisational level, differences were less marked at a systems (industry) level, with many common understandings carried over from the pre-corporatised operating environment. These Heritage Factors were central to understanding the systems level cohesion noted in the work. The findings of this study are intended to contribute to a body of knowledge encompassing resilience and high reliability in critical infrastructure industries. The research also has value from a practical perspective, as it suggests a range of opportunities to enhance resilient functioning under increasingly interdependent, networked conditions.

On the data consumption benefits of accepting increased uncertainty

In the context of learning paradigms of identification in the limit, we address the question: why is uncertainty sometimes desirable? We use mind change bounds on the output hypotheses as a measure of uncertainty, and interpret ‘desirable’ as reduction in data memorization, also defined in terms of mind change bounds. The resulting model is closely related to iterative learning with bounded mind change complexity, but the dual use of mind change bounds — for hypotheses and for data — is a key distinctive feature of our approach. We show that situations exists where the more mind changes the learner is willing to accept, the lesser the amount of data it needs to remember in order to converge to the correct hypothesis. We also investigate relationships between our model and learning from good examples, set-driven, monotonic and strong-monotonic learners, as well as class-comprising versus class-preserving learnability.

Probabilistic subgroup identification using Bayesian finite mixture modelling : a case study in Parkinson’s disease phenotype identification

This article explores the use of probabilistic classification, namely finite mixture modelling, for identification of complex disease phenotypes, given cross-sectional data. In particular, if focuses on posterior probabilities of subgroup membership, a standard output of finite mixture modelling, and how the quantification of uncertainty in these probabilities can lead to more detailed analyses. Using a Bayesian approach, we describe two practical uses of this uncertainty: (i) as a means of describing a person’s membership to a single or multiple latent subgroups and (ii) as a means of describing identified subgroups by patient-centred covariates not included in model estimation. These proposed uses are demonstrated on a case study in Parkinson’s disease (PD), where latent subgroups are identified using multiple symptoms from the Unified Parkinson’s Disease Rating Scale (UPDRS).

An approach to access control under uncertainty

In dynamic and uncertain environments such as healthcare, where the needs of security and information availability are difficult to balance, an access control approach based on a static policy will be suboptimal regardless of how comprehensive it is. The uncertainty stems from the unpredictability of users’ operational needs as well as their private incentives to misuse permissions. In Role Based Access Control (RBAC), a user’s legitimate access request may be denied because its need has not been anticipated by the security administrator. Alternatively, even when the policy is correctly specified an authorised user may accidentally or intentionally misuse the granted permission. This paper introduces a novel approach to access control under uncertainty and presents it in the context of RBAC. By taking insights from the field of economics, in particular the insurance literature, we propose a formal model where the value of resources are explicitly defined and an RBAC policy (entailing those predictable access needs) is only used as a reference point to determine the price each user has to pay for access, as opposed to representing hard and fast rules that are always rigidly applied.

REGAL : a regularization based algorithm for reinforcement learning in weakly communicating MDPs

We provide an algorithm that achieves the optimal regret rate in an unknown weakly communicating Markov Decision Process (MDP). The algorithm proceeds in episodes where, in each episode, it picks a policy using regularization based on the span of the optimal bias vector. For an MDP with S states and A actions whose optimal bias vector has span bounded by H, we show a regret bound of ~ O(HS p AT ). We also relate the span to various diameter-like quantities associated with the MDP, demonstrating how our results improve on previous regret bounds.

Using the Precede-Proceed Model of Health Program Planning in breast cancer nursing research

Aim: In this paper we discuss the use of the Precede-Proceed model when investigating health promotion options for breast cancer survivors. Background: Adherence to recommended health behaviors can optimize well-being after cancer treatment. Guided by the Precede-Proceed approach, we studied the behaviors of breast cancer survivors in our health service area. Data sources: The interview data from the cohort of breast cancer survivors are used in this paper to illustrate the use of Precede-Proceed in this nursing research context. Interview data were collected from June to December 2009. We also searched Medline, CINAHL, PsychInfo and PsychExtra up to 2010 for relevant literature in English to interrogate the data from other theoretical perspectives. Discussion: The Precede-Proceed model is theoretically-complex. The deductive analytic process guided by the model usefully explained some of the health behaviors of cancer survivors, although it could not explicate many other findings. A complementary inductive approach to the analysis and subsequent interpretation by way of Uncertainty in Illness Theory and other psychosocial perspectives provided a comprehensive account of the qualitative data that resulted in contextually-relevant recommendations for nursing practice. Implications for nursing: Nursing researchers using Precede-Proceed should maintain theoretical flexibility when interpreting qualitative data. Perspectives not embedded in the model might need to be considered to ensure that the data are analyzed in a contextually-relevant way. Conclusion: Precede-Proceed provides a robust framework for nursing researchers investigating health promotion in cancer survivors; however additional theoretical lenses to those embedded in the model can enhance data interpretation.

Adaptive wing/aerofoil design optimisation using MOEA coupled to uncertainty design method

The use of adaptive wing/aerofoil designs is being considered as promising techniques in aeronautic/aerospace since they can reduce aircraft emissions, improve aerodynamic performance of manned or unmanned aircraft. The paper investigates the robust design and optimisation for one type of adaptive techniques; Active Flow Control (AFC) bump at transonic flow conditions on a Natural Laminar Flow (NLF) aerofoil designed to increase aerodynamic efficiency (especially high lift to drag ratio). The concept of using Shock Control Bump (SCB) is to control supersonic flow on the suction/pressure side of NLF aerofoil: RAE 5243 that leads to delaying shock occurrence or weakening its strength. Such AFC technique reduces total drag at transonic speeds due to reduction of wave drag. The location of Boundary Layer Transition (BLT) can influence the position the supersonic shock occurrence. The BLT position is an uncertainty in aerodynamic design due to the many factors, such as surface contamination or surface erosion. The paper studies the SCB shape design optimisation using robust Evolutionary Algorithms (EAs) with uncertainty in BLT positions. The optimisation method is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing and asynchronous evaluation. Two test cases are conducted; the first test assumes the BLT is at 45% of chord from the leading edge and the second test considers robust design optimisation for SCB at the variability of BLT positions and lift coefficient. Numerical result shows that the optimisation method coupled to uncertainty design techniques produces Pareto optimal SCB shapes which have low sensitivity and high aerodynamic performance while having significant total drag reduction.

Risk-informed thinking in airports: the application of business continuity management in airport infrastructure

Airports worldwide represent key forms of critical infrastructure in addition to serving as nodes in the international aviation network. While the continued operation of airports is critical to the functioning of reliable air passenger and freight transportation, these infrastructure systems face a number of sources of disturbance that threaten their operational viability. Recent examples of high magnitude events include the eruption of Iceland’s Eyjafjallajokull volcano eruption (Folattau and Schofield 2010), the failure of multiple systems at the opening of Heathrow’s Terminal 5 (Brady and Davies 2010) and the Glasgow airport 2007 terrorist attack (Crichton 2008). While these newsworthy events do occur, a multitude of lower-level more common disturbances also have the potential to cause significant discontinuity to airport operations. Regional airports face a unique set of challenges, particularly in a nation like Australia where they serve to link otherwise remote and isolated communities to metropolitan hubs (Wheeler 2005), often without the resources and political attention received by larger capital city airports. This paper discusses conceptual relationships between Business Continuity Management (BCM) and High Reliability Theory, and proposes BCM as an appropriate risk-based management process to ensure continued airport operation in the face of uncertainty. In addition, it argues that that correctly implemented BCM can lead to highly reliable organisations. This is framed within the broader context of critical infrastructures and the need for adequate crisis management approaches suited to their unique requirements (Boin and McConnell 2007).

Cellulosic ethanol from sugarcane bagasse in Australia : exploring industry feasibility through systems analysis, techno-economic assessment and pilot plant development

Overcoming many of the constraints to early stage investment in biofuels production from sugarcane bagasse in Australia requires an understanding of the complex technical, economic and systemic challenges associated with the transition of established sugar industry structures from single product agri-businesses to new diversified multi-product biorefineries. While positive investment decisions in new infrastructure requires technically feasible solutions and the attainment of project economic investment thresholds, many other systemic factors will influence the investment decision. These factors include the interrelationships between feedstock availability and energy use, competing product alternatives, technology acceptance and perceptions of project uncertainty and risk. This thesis explores the feasibility of a new cellulosic ethanol industry in Australia based on the large sugarcane fibre (bagasse) resource available. The research explores industry feasibility from multiple angles including the challenges of integrating ethanol production into an established sugarcane processing system, scoping the economic drivers and key variables relating to bioethanol projects and considering the impact of emerging technologies in improving industry feasibility. The opportunities available from pilot scale technology demonstration are also addressed. Systems analysis techniques are used to explore the interrelationships between the existing sugarcane industry and the developing cellulosic biofuels industry. This analysis has resulted in the development of a conceptual framework for a bagassebased cellulosic ethanol industry in Australia and uses this framework to assess the uncertainty in key project factors and investment risk. The analysis showed that the fundamental issue affecting investment in a cellulosic ethanol industry from sugarcane in Australia is the uncertainty in the future price of ethanol and government support that reduces the risks associated with early stage investment is likely to be necessary to promote commercialisation of this novel technology. Comprehensive techno-economic models have been developed and used to assess the potential quantum of ethanol production from sugarcane in Australia, to assess the feasibility of a soda-based biorefinery at the Racecourse Sugar Mill in Mackay, Queensland and to assess the feasibility of reducing the cost of production of fermentable sugars from the in-planta expression of cellulases in sugarcane in Australia. These assessments show that ethanol from sugarcane in Australia has the potential to make a significant contribution to reducing Australia’s transportation fuel requirements from fossil fuels and that economically viable projects exist depending upon assumptions relating to product price, ethanol taxation arrangements and greenhouse gas emission reduction incentives. The conceptual design and development of a novel pilot scale cellulosic ethanol research and development facility is also reported in this thesis. The establishment of this facility enables the technical and economic feasibility of new technologies to be assessed in a multi-partner, collaborative environment. As a key outcome of this work, this study has delivered a facility that will enable novel cellulosic ethanol technologies to be assessed in a low investment risk environment, reducing the potential risks associated with early stage investment in commercial projects and hence promoting more rapid technology uptake. While the study has focussed on an exploration of the feasibility of a commercial cellulosic ethanol industry from sugarcane in Australia, many of the same key issues will be of relevance to other sugarcane industries throughout the world seeking diversification of revenue through the implementation of novel cellulosic ethanol technologies.