In this thesis we develop several kinds of latent variable models in order to address three types of bio-statistical problem. The three problems are the treatment effect of carcinogens on tumour development, spatial interactions between plant species and motor unit number estimation (MUNE). The three types of data looked at are: highly heterogeneous longitudinal count data, quadrat counts of species on a rectangular lattice and lastly, electrophysiological data consisting of measurements of compound muscle action potential (CMAP) area and amplitude. Chapter 1 sets out the structure and the development of ideas presented in this thesis from the point of view of: model structure, model selection, and efficiency of estimation. Chapter 2 is an introduction to the relevant literature that has in influenced the development of this thesis. In Chapter 3 we use the EM algorithm for an application of an autoregressive hidden Markov model to describe longitudinal counts. The data is collected from experiments to test the effect of carcinogens on tumour growth in mice. Here we develop forward and backward recursions for calculating the likelihood and for estimation. Chapter 4 is the analysis of a similar kind of data using a more sophisticated model, incorporating random effects, but estimation this time is conducted from the Bayesian perspective. Bayesian model selection is also explored. In Chapter 5 we move to the two dimensional lattice and construct a model for describing the spatial interaction of tree types. We also compare the merits of directed and undirected graphical models for describing the hidden lattice. Chapter 6 is the application of a Bayesian hierarchical model (MUNE), where the latent variable this time is multivariate Gaussian and dependent on a covariate, the stimulus. Model selection is carried out using the Bayes Information Criterion (BIC). In Chapter 7 we approach the same problem by using the reversible jump methodology (Green, 1995) where this time we use a dual Gaussian-Binary representation of the latent data. We conclude in Chapter 8 with suggestions for the direction of new work. In this thesis, all of the estimation carried out on real data has only been performed once we have been satisfied that estimation is able to retrieve the parameters from simulated data. Keywords: Amyotrophic lateral sclerosis (ALS), carcinogens, hidden Markov models (HMM), latent variable models, longitudinal data analysis, motor unit disease (MND), partially ordered Markov models (POMMs), the pseudo auto- logistic model, reversible jump, spatial interactions.

The primary objective of this dissertation is to utilise, adapt and extend current stochastic models and statistical inference techniques to describe the transmission of nosocomial pathogens, i.e. hospital-acquired pathogens, and multiply-resistant organisms within the hospital setting. The emergence of higher levels of antibiotic resistance is threatening the long term viability of current treatment options and placing greater emphasis on the use of infection control procedures. The relative importance and value of various infection control practices is often debated and there is a lack of quantitative evidence concerning their effectiveness. The methods developed in this dissertation are applied to data of methicillin-resistant Staphylococcus aureus occurrence in intensive care units to quantify the effectiveness of infection control procedures. Analysis of infectious disease or carriage data is complicated by dependencies within the data and partial observation of the transmission process. Dependencies within the data are inherent because the risk of colonisation depends on the number of other colonised individuals. The colonisation times, chain and duration are often not visible to the human eye making only partial observation of the transmission process possible. Within a hospital setting, routine surveillance monitoring permits knowledge of interval-censored colonisation times. However, consideration needs to be given to the possibility of false negative outcomes when relying on observations from routine surveillance monitoring. SI (Susceptible, Infected) models are commonly used to describe community epidemic processes and allow for any inherent dependencies. Statistical inference techniques, such as the expectation-maximisation (EM) algorithm and Markov chain Monte Carlo (MCMC) can be used to estimate the model parameters when only partial observation of the epidemic process is possible. These methods appear well suited for the analysis of hospital infectious disease data but need to be adapted for short patient stays through migration. This thesis focuses on the use of Bayesian statistics to explore the posterior distributions of the unknown parameters. MCMC techniques are introduced to overcome analytical intractability caused by partial observation of the epidemic process. Statistical issues such as model adequacy and MCMC convergence assessment are discussed throughout the thesis. The new methodology allows the quantification of the relative importance of different transmission routes and the benefits of hospital practices, in terms of changed transmission rates. Evidence-based decisions can therefore be made on the impact of infection control procedures which is otherwise difficult on the basis of clinical studies alone. The methods are applied to data describing the occurrence of methicillin-resistant Staphylococcus aureus within intensive care units in hospitals in Brisbane and London

In this thesis a number of statistical methods have been developed and applied to habitat suitability modelling for rare and threatened species. Data available on these species are typically limited. Therefore, developing these models from these data can be problematic and may produce prediction biases. To address these problems there are three aims of this thesis. The _rst aim is to develop and implement frequentist and Bayesian statistical modelling approaches for these types of data. The second aim is develop and implement expert elicitation methods. The third aim is to apply these novel approaches to Australian rare and threatened species case studies with the intention of habitat suitability modelling. The _rst aim is ful_lled by investigating two innovative approaches for habitat suitability modelling and sensitivity analysis of the second approach to priors. The _rst approach is a new multilevel framework developed to model the species distribution at multiple scales and identify excess zeros (absences outside the species range). Applying a statistical modelling approach to the identi_cation of excess zeros has not previously been conducted. The second approach is an extension and application of Bayesian classi_cation trees to modelling the habitat suitability of a threatened species. This is the _rst `real' application of this approach in ecology. Lastly, sensitivity analysis of the priors in Bayesian classi_cation trees are examined for a real case study. Previously, sensitivity analysis of this approach to priors has not been examined. To address the second aim, expert elicitation methods are developed, extended and compared in this thesis. In particular, one elicitation approach is extended from previous research, there is a comparison of three elicitation methods, and one new elicitation approach is proposed. These approaches are illustrated for habitat suitability modelling of a rare species and the opinions of one or two experts are elicited. The _rst approach utilises a simple questionnaire, in which expert opinion is elicited on whether increasing values of a covariate either increases, decreases or does not substantively impact on a response. This approach is extended to express this information as a mixture of three normally distributed prior distributions, which are then combined with available presence/absence data in a logistic regression. This is one of the _rst elicitation approaches within the habitat suitability modelling literature that is appropriate for experts with limited statistical knowledge and can be used to elicit information from single or multiple experts. Three relatively new approaches to eliciting expert knowledge in a form suitable for Bayesian logistic regression are compared, one of which is the questionnaire approach. Included in this comparison of three elicitation methods are a summary of the advantages and disadvantages of these three methods, the results from elicitations and comparison of the prior and posterior distributions. An expert elicitation approach is developed for classi_cation trees, in which the size and structure of the tree is elicited. There have been numerous elicitation approaches proposed for logistic regression, however no approaches have been suggested for classi_cation trees. The last aim of this thesis is addressed in all chapters, since the statistical approaches proposed and extended in this thesis have been applied to real case studies. Two case studies have been examined in this thesis. The _rst is the rare native Australian thistle (Stemmacantha australis), in which the dataset contains a large number of absences distributed over the majority of Queensland, and a small number of presence sites that are only within South-East Queensland. This case study motivated the multilevel modelling framework. The second case study is the threatened Australian brush-tailed rock-wallaby (Petrogale penicillata). The application and sensitivity analysis of Bayesian classi_cation trees, and all expert elicitation approaches investigated in this thesis are applied to this case study. This work has several implications for conservation and management of rare and threatened species. Novel statistical approaches addressing the _rst aim provide extensions to currently existing methods, or propose a new approach, for identi _cation of current and potential habitat. We demonstrate that better model predictions can be achieved using each method, compared to standard techniques. Elicitation approaches addressing the second aim ensure expert knowledge in various forms can be harnessed for habitat modelling, a particular bene_t for rare and threatened species which typically have limited data. Throughout, innovations in statistical methodology are both motivated and illustrated via habitat modelling for two rare and threatened species: the native thistle Stemmacantha australis and the brush-tailed rock wallaby Petrogale penicillata.