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.

Effect of soil parameter uncertainty on seismic response of buried segmented pipeline

Pipelines are important lifeline facilities spread over a large area and they generally encounter a range of seismic hazards and different soil conditions. The seismic response of a buried segmented pipe depends on various parameters such as the type of buried pipe material and joints, end restraint conditions, soil characteristics, burial depths, and earthquake ground motion, etc. This study highlights the effect of the variation of geotechnical properties of the surrounding soil on seismic response of a buried pipeline. The variations of the properties of the surrounding soil along the pipe are described by sampling them from predefined probability distribution. The soil-pipe interaction model is developed in OpenSEES. Nonlinear earthquake time-history analysis is performed to study the effect of soil parameters variability on the response of pipeline. Based on the results, it is found that uncertainty in soil parameters may result in significant response variability of the pipeline.

Temporal boundary objects in megaprojects : mapping the system with the integrated master schedule

Recently, a stream of project management research has recognized the critical role of boundary objects in the organization of projects. In this paper, we investigate how one advanced scheduling tool, the Integrated Master Schedule (IMS), is used as a temporal boundary object at various stages of complex projects. The IMS is critical to megaprojects which typically span long periods of time and face a high degree of complexity and uncertainty. In this paper, we conceptualize projects of this type as complex adaptive systems (CAS). We report the findings of four case projects on how the IMS mapped interactions, interdependencies, constraints, and fractal patterns of these emerging projects, and how the process of IMS visualization enabled communication and negotiation of project realities. This paper highlights that this advanced timeline tool acts as a boundary object and elicits shared understanding of complex projects from their stakeholders.

Uncertainty analysis of pollutant build-up modelling based on a Bayesian Weighted Least Squares approach

Reliable pollutant build-up prediction plays a critical role in the accuracy of urban stormwater quality modelling outcomes. However, water quality data collection is resource demanding compared to streamflow data monitoring, where a greater quantity of data is generally available. Consequently, available water quality data sets span only relatively short time scales unlike water quantity data. Therefore, the ability to take due consideration of the variability associated with pollutant processes and natural phenomena is constrained. This in turn gives rise to uncertainty in the modelling outcomes as research has shown that pollutant loadings on catchment surfaces and rainfall within an area can vary considerably over space and time scales. Therefore, the assessment of model uncertainty is an essential element of informed decision making in urban stormwater management. This paper presents the application of a range of regression approaches such as ordinary least squares regression, weighted least squares Regression and Bayesian Weighted Least Squares Regression for the estimation of uncertainty associated with pollutant build-up prediction using limited data sets. The study outcomes confirmed that the use of ordinary least squares regression with fixed model inputs and limited observational data may not provide realistic estimates. The stochastic nature of the dependent and independent variables need to be taken into consideration in pollutant build-up prediction. It was found that the use of the Bayesian approach along with the Monte Carlo simulation technique provides a powerful tool, which attempts to make the best use of the available knowledge in the prediction and thereby presents a practical solution to counteract the limitations which are otherwise imposed on water quality modelling.

Sensitivity of peak positions to flight-path parameters in a deep-inelastic scattering neutron TOF spectrometer

The effects of small changes in flight-path parameters (primary and secondary flight paths, detector angles), and of displacement of the sample along the beam axis away from its ideal position, are examined for an inelastic time-of-flight (TOF) neutron spectrometer, emphasising the deep-inelastic regime. The aim was to develop a rational basis for deciding what measured shifts in the positions of spectral peaks could be regarded as reliable in the light of the uncertainties in the calibrated flight-path parameters. Uncertainty in the length of the primary or secondary flight path has the least effect on the positions of the peaks of H, D and He, which are dominated by the accuracy of the calibration of the detector angles. This aspect of the calibration of a TOF spectrometer therefore demands close attention to achieve reliable outcomes where the position of the peaks is of significant scientific interest and is discussed in detail. The corresponding sensitivities of the position of peak of the Compton profile, J(y), to flight-path parameters and sample position are also examined, focusing on the comparability across experiments of results for H, D and He. We show that positioning the sample to within a few mm of the ideal position is required to ensure good comparability between experiments if data from detectors at high forward angles are to be reliably interpreted.

Livestock production in a changing climate : adaptation and mitigation research in Australia

Climate change presents a range of challenges for animal agriculture in Australia. Livestock production will be affected by changes in temperature and water availability through impacts on pasture and forage crop quantity and quality, feed-grain production and price, and disease and pest distributions. This paper provides an overview of these impacts and the broader effects on landscape functionality, with a focus on recent research on effects of increasing temperature, changing rainfall patterns, and increased climate variability on animal health, growth, and reproduction, including through heat stress, and potential adaptation strategies. The rate of adoption of adaptation strategies by livestock producers will depend on perceptions of the uncertainty in projected climate and regional-scale impacts and associated risk. However, management changes adopted by farmers in parts of Australia during recent extended drought and associated heatwaves, trends consistent with long-term predicted climate patterns, provide some insights into the capacity for practical adaptation strategies. Animal production systems will also be significantly affected by climate change policy and national targets to address greenhouse gas emissions, since livestock are estimated to contribute ~10% of Australia’s total emissions and 8–11% of global emissions, with additional farm emissions associated with activities such as feed production. More than two-thirds of emissions are attributed to ruminant animals. This paper discusses the challenges and opportunities facing livestock industries in Australia in adapting to and mitigating climate change. It examines the research needed to better define practical options to reduce the emissions intensity of livestock products, enhance adaptation opportunities, and support the continued contribution of animal agriculture to Australia’s economy, environment, and regional communities.

Segmental torso masses and coronal plane joint torques in the adolescent scoliotic spine

Introduction. Calculating segmental (vertebral level-by-level) torso masses in Adolescent Idiopathic Scoliosis (AIS) patients allows the gravitational loading on the scoliotic spine during relaxed standing to be determined. This study used CT scans of AIS patients to measure segmental torso masses and explores how joint moments in the coronal plane are affected by changes in the position of the intervertebral joint’s axis of rotation; particularly at the apex of a scoliotic major curve. Methods. Existing low dose CT data from the Paediatric Spine Research Group was used to calculate vertebral level-by-level torso masses and joint torques occurring in the spine for a group of 20 female AIS patients (mean age 15.0 ± 2.7 years, mean Cobb angle 53 ± 7.1°). Image processing software, ImageJ (v1.45 NIH USA) was used to threshold the T1 to L5 CT images and calculate the segmental torso volume and mass corresponding to each vertebral level. Body segment masses for the head, neck and arms were taken from published anthropometric data. Intervertebral (IV) joint torques at each vertebral level were found using principles of static equilibrium together with the segmental body mass data. Summing the torque contributions for each level above the required joint, allowed the cumulative joint torque at a particular level to be found. Since there is some uncertainty in the position of the coronal plane Instantaneous Axis of Rotation (IAR) for scoliosis patients, it was assumed the IAR was located in the centre of the IV disc. A sensitivity analysis was performed to see what effect the IAR had on the joint torques by moving it laterally 10mm in both directions. Results. The magnitude of the torso masses from T1-L5 increased inferiorly, with a 150% increase in mean segmental torso mass from 0.6kg at T1 to 1.5kg at L5. The magnitudes of the calculated coronal plane joint torques during relaxed standing were typically 5-7 Nm at the apex of the curve, with the highest apex joint torque of 7Nm being found in patient 13. Shifting the assumed IAR by 10mm towards the convexity of the spine, increased the joint torque at that level by a mean 9.0%, showing that calculated joint torques were moderately sensitive to the assumed IAR location. When the IAR midline position was moved 10mm away from the convexity of the spine, the joint torque reduced by a mean 8.9%. Conclusion. Coronal plane joint torques as high as 7Nm can occur during relaxed standing in scoliosis patients, which may help to explain the mechanics of AIS progression. This study provides new anthropometric reference data on vertebral level-by-level torso mass in AIS patients which will be useful for biomechanical models of scoliosis progression and treatment. However, the CT scans were performed in supine (no gravitational load on spine) and curve magnitudes are known to be smaller than those measured in standing.

Cost-effectiveness of a telephone-delivered education programme to prevent early childhood caries in a disadvantaged area : a cohort study

Objectives Early childhood caries is a highly destructive dental disease which is compounded by the need for young children to be treated under general anaesthesia. In Australia, there are long waiting periods for treatment at public hospitals. In this paper, we examined the costs and patient outcomes of a prevention programme for early childhood caries to assess its value for government services. Design Cost-effectiveness analysis using a Markov model. Setting Public dental patients in a low socioeconomic, socially disadvantaged area in the State of Queensland, Australia. Participants Children aged 6 months to 6 years received either a telephone prevention programme or usual care. Primary and secondary outcome measures A mathematical model was used to assess caries incidence and public dental treatment costs for a cohort of children. Healthcare costs, treatment probabilities and caries incidence were modelled from 6 months to 6 years of age based on trial data from mothers and their children who received either a telephone prevention programme or usual care. Sensitivity analyses were used to assess the robustness of the findings to uncertainty in the model estimates. Results By age 6 years, the telephone intervention programme had prevented an estimated 43 carious teeth and saved £69 984 in healthcare costs per 100 children. The results were sensitive to the cost of general anaesthesia (cost-savings range £36 043–£97 298) and the incidence of caries in the prevention group (cost-savings range £59 496–£83 368) and usual care (cost-savings range £46 833–£93 328), but there were cost savings in all scenarios. Conclusions A telephone intervention that aims to prevent early childhood caries is likely to generate considerable and immediate patient benefits and cost savings to the public dental health service in disadvantaged communities.

A near-to-far non-parametric learning approach for estimating traversability in deformable terrain

It is well recognized that many scientifically interesting sites on Mars are located in rough terrains. Therefore, to enable safe autonomous operation of a planetary rover during exploration, the ability to accurately estimate terrain traversability is critical. In particular, this estimate needs to account for terrain deformation, which significantly affects the vehicle attitude and configuration. This paper presents an approach to estimate vehicle configuration, as a measure of traversability, in deformable terrain by learning the correlation between exteroceptive and proprioceptive information in experiments. We first perform traversability estimation with rigid terrain assumptions, then correlate the output with experienced vehicle configuration and terrain deformation using a multi-task Gaussian Process (GP) framework. Experimental validation of the proposed approach was performed on a prototype planetary rover and the vehicle attitude and configuration estimate was compared with state-of-the-art techniques. We demonstrate the ability of the approach to accurately estimate traversability with uncertainty in deformable terrain.

Traversability estimation for a planetary rover via experimental kernel learning in a Gaussian process framework

A critical requirement for safe autonomous navigation of a planetary rover is the ability to accurately estimate the traversability of the terrain. This work considers the problem of predicting the attitude and configuration angles of the platform from terrain representations that are often incomplete due to occlusions and sensor limitations. Using Gaussian Processes (GP) and exteroceptive data as training input, we can provide a continuous and complete representation of terrain traversability, with uncertainty in the output estimates. In this paper, we propose a novel method that focuses on exploiting the explicit correlation in vehicle attitude and configuration during operation by learning a kernel function from vehicle experience to perform GP regression. We provide an extensive experimental validation of the proposed method on a planetary rover. We show significant improvement in the accuracy of our estimation compared with results obtained using standard kernels (Squared Exponential and Neural Network), and compared to traversability estimation made over terrain models built using state-of-the-art GP techniques.

Distribution harmonic state estimation based on a modified PSO considering parameters uncertainty

This paper presents a new algorithm based on a Modified Particle Swarm Optimization (MPSO) to estimate the harmonic state variables in a distribution networks. The proposed algorithm performs the estimation for both amplitude and phase of each injection harmonic currents by minimizing the error between the measured values from Phasor Measurement Units (PMUs) and the values computed from the estimated parameters during the estimation process. The proposed algorithm can take into account the uncertainty of the harmonic pseudo measurement and the tolerance in the line impedances of the network as well as the uncertainty of the Distributed Generators (DGs) such as Wind Turbines (WTs). The main features of the proposed MPSO algorithm are usage of a primary and secondary PSO loop and applying the mutation function. The simulation results on 34-bus IEEE radial and a 70-bus realistic radial test networks are presented. The results demonstrate that the speed and the accuracy of the proposed Distribution Harmonic State Estimation (DHSE) algorithm are very excellent compared to the algorithms such as Weight Least Square (WLS), Genetic Algorithm (GA), original PSO, and Honey Bees Mating Optimization (HBMO).

Distribution harmonic state estimation based on a hybrid PSO and SA algorithm considering parameters uncertainty

This paper presents a new algorithm based on a Hybrid Particle Swarm Optimization (PSO) and Simulated Annealing (SA) called PSO-SA to estimate harmonic state variables in distribution networks. The proposed algorithm performs estimation for both amplitude and phase of each harmonic currents injection by minimizing the error between the measured values from Phasor Measurement Units (PMUs) and the values computed from the estimated parameters during the estimation process. The proposed algorithm can take into account the uncertainty of the harmonic pseudo measurement and the tolerance in the line impedances of the network as well as uncertainty of the Distributed Generators (DGs) such as Wind Turbines (WT). The main feature of proposed PSO-SA algorithm is to reach quickly around the global optimum by PSO with enabling a mutation function and then to find that optimum by SA searching algorithm. Simulation results on IEEE 34 bus radial and a realistic 70-bus radial test networks are presented to demonstrate the speed and accuracy of proposed Distribution Harmonic State Estimation (DHSE) algorithm is extremely effective and efficient in comparison with the conventional algorithms such as Weight Least Square (WLS), Genetic Algorithm (GA), original PSO and Honey Bees Mating Optimization (HBMO) algorithm.

Factors affecting the extraction of absorbed dose information in a 3D polymer gel dosimeter by X ray computed tomography (IAEA-CN-96/122P)

Two sources of uncertainty in the X ray computed tomography imaging of polymer gel dosimeters are investigated in the paper.The first cause is a change in postirradiation density, which is proportional to the computed tomography signal and is associated with a volume change. The second cause of uncertainty is reconstruction noise.A simple technique that increases the residual signal to noise ratio by almost two orders of magnitude is examined.

Monte Carlo simulations of small field output factors in solid phantoms

Introduction Total scatter factor (or output factor) in megavoltage photon dosimetry is a measure of relative dose relating a certain field size to a reference field size. The use of solid phantoms has been well established for output factor measurements, however to date these phantoms have not been tested with small fields. In this work, we evaluate the water equivalency of a number of solid phantoms for small field output factor measurements using the EGSnrc Monte Carlo code. Methods The following small square field sizes were simulated using BEAMnrc: 5, 6, 7, 8, 10 and 30 mm. Each simulated phantom geometry was created in DOSXYZnrc and consisted of a silicon diode (of length and width 1.5 mm and depth 0.5 mm) submersed in the phantom at a depth of 5 g/cm2. The source-to-detector distance was 100 cm for all simulations. The dose was scored in a single voxel at the location of the diode. Interaction probabilities and radiation transport parameters for each material were created using custom PEGS4 files. Results A comparison of the resultant output factors in the solid phantoms, compared to the same factors in a water phantom are shown in Fig. 1. The statistical uncertainty in each point was less than or equal to 0.4 %. The results in Fig. 1 show that the density of the phantoms affected the output factor results, with higher density materials (such as PMMA) resulting in higher output factors. Additionally, it was also calculated that scaling the depth for equivalent path length had negligible effect on the output factor results at these field sizes. Discussion and conclusions Electron stopping power and photon mass energy absorption change minimally with small field size [1]. Also, it can be seen from Fig. 1 that the difference from water decreases with increasing field size. Therefore, the most likely cause for the observed discrepancies in output factors is differing electron disequilibrium as a function of phantom density. When measuring small field output factors in a solid phantom, it is important that the density is very close to that of water.

Bioeconomic modelling and risk assessment of tiger prawn (Penaeus esculentus) stock enhancement in Exmouth Gulf, Australia

A bioeconomic model was developed to evaluate the potential performance of brown tiger prawn stock enhancement in Exmouth Gulf, Australia. This paper presents the framework for the bioeconomic model and risk assessment for all components of a stock enhancement operation, i.e. hatchery, grow-out, releasing, population dynamics, fishery, and monitoring, for a commercial scale enhancement of about 100 metric tonnes, a 25% increase in average annual catch in Exmouth Gulf. The model incorporates uncertainty in estimates of parameters by using a distribution for the parameter over a certain range, based on experiments, published data, or similar studies. Monte Carlo simulation was then used to quantify the effects of these uncertainties on the model-output and on the economic potential of a particular production target. The model incorporates density-dependent effects in the nursery grounds of brown tiger prawns. The results predict that a release of 21 million 1 g prawns would produce an estimated enhanced prawn catch of about 100 t. This scale of enhancement has a 66.5% chance of making a profit. The largest contributor to the overall uncertainty of the enhanced prawn catch was the post-release mortality, followed by the density-dependent mortality caused by released prawns. These two mortality rates are most difficult to estimate in practice and are much under-researched in stock enhancement.