Bayesian models for longitudinal data

Longitudinal data, where data are repeatedly observed or measured on a temporal basis of time or age provides the foundation of the analysis of processes which evolve over time, and these can be referred to as growth or trajectory models. One of the traditional ways of looking at growth models is to employ either linear or polynomial functional forms to model trajectory shape, and account for variation around an overall mean trend with the inclusion of random eects or individual variation on the functional shape parameters. The identification of distinct subgroups or sub-classes (latent classes) within these trajectory models which are not based on some pre-existing individual classification provides an important methodology with substantive implications. The identification of subgroups or classes has a wide application in the medical arena where responder/non-responder identification based on distinctly diering trajectories delivers further information for clinical processes. This thesis develops Bayesian statistical models and techniques for the identification of subgroups in the analysis of longitudinal data where the number of time intervals is limited. These models are then applied to a single case study which investigates the neuropsychological cognition for early stage breast cancer patients undergoing adjuvant chemotherapy treatment from the Cognition in Breast Cancer Study undertaken by the Wesley Research Institute of Brisbane, Queensland. Alternative formulations to the linear or polynomial approach are taken which use piecewise linear models with a single turning point, change-point or knot at a known time point and latent basis models for the non-linear trajectories found for the verbal memory domain of cognitive function before and after chemotherapy treatment. Hierarchical Bayesian random eects models are used as a starting point for the latent class modelling process and are extended with the incorporation of covariates in the trajectory profiles and as predictors of class membership. The Bayesian latent basis models enable the degree of recovery post-chemotherapy to be estimated for short and long-term followup occasions, and the distinct class trajectories assist in the identification of breast cancer patients who maybe at risk of long-term verbal memory impairment.

The effects of pore architecture in silk fibroin scaffolds on the growth and differentiation of mesenchymal stem cells expressing BMP7

The pore architecture of scaffolds is known to play a critical role in tissue engineering as it provides the vital framework for seeded cells to organize into a functioning tissue. In this report we have investigated the effects of different concentrations of silk fibroin protein on three-dimensional (3D) scaffold pore microstructure. Four pore size ranges of silk fibroin scaffolds were made by the freeze drying technique, with the pore sizes ranging from 50 to 300 lm. The pore sizes of the scaffolds decreased as the concentration of fibroin protein increased. Human bone marrow mesenchymal stromal cells (BMSC) transfected with the BMP7 gene were cultured in these scaffolds. A cell viability colorimetric assay, alkaline phosphatase assay and reverse transcription-polymerase chain reaction were performed to analyze the effect of pore size on cell growth, the secretion of extracellular matrix (ECM) and osteogenic differentiation. Cell migration in 3D scaffolds was confirmed by confocal microscopy. Calvarial defects in SCID mice were used to determine the bone forming ability of the silk fibroin scaffolds incorporating BMSC expressing BMP7. The results showed that BMSC expressing BMP7 preferred a pore size between 100 and 300 lm in silk fibroin protein fabricated scaffolds, with better cell proliferation and ECM production. Furthermore, in vivo transplantation of the silk fibroin scaffolds combined with BMSC expressing BMP7 induced new bone formation. This study has shown that an optimized pore architecture of silk fibroin scaffolds can modulate the bioactivity of BMP7-transfected BMSC in bone formation.

Development of pollutant build-up parameters for MIKE URBAN for Southeast Queensland, Australia

Accurate estimation of input parameters is essential to ensure the accuracy and reliability of hydrologic and water quality modelling. Calibration is an approach to obtain accurate input parameters for comparing observed and simulated results. However, the calibration approach is limited as it is only applicable to catchments where monitoring data is available. Therefore, methodology to estimate appropriate model input parameters is critical, particularly for catchments where monitoring data is not available. In the research study discussed in the paper, pollutant build-up parameters derived from catchment field investigations and model calibration using MIKE URBAN are compared for three catchments in Southeast Queensland, Australia. Additionally, the sensitivity of MIKE URBAN input parameters was analysed. It was found that Reduction Factor is the most sensitive parameter for peak flow and total runoff volume estimation whilst Build-up rate is the most sensitive parameter for TSS load estimation. Consequently, these input parameters should be determined accurately in hydrologic and water quality simulations using MIKE URBAN. Furthermore, an empirical equation for Southeast Queensland, Australia for the conversion of build-up parameters derived from catchment field investigations as MIKE URBAN input build-up parameters was derived. This will provide guidance for allowing for regional variations in the estimation of input parameters for catchment modelling using MIKE URBAN where monitoring data is not available.

Nitrogen and phosphorus transformations in fixed-film biofilters subjected to aeration/no-aeration cycles

Despite recent developments in fixed-film combined biological nutrients removal (BNR) technology; fixed-film systems (i.e., biofilters), are still at the early stages of development and their application has been limited to a few laboratory-scale experiments. Achieving enhanced biological phosphorus removal in fixed-film systems requires exposing the micro-organisms and the waste stream to alternating anaerobic/aerobic or anaerobic/anoxic conditions in cycles. The concept of cycle duration (CD) as a process control parameter is unique to fixed-film BNR systems, has not been previously investigated, and can be used to optimise the performance of such systems. The CD refers to the elapsed time before the biomass is re-exposed to the same environmental conditions in cycles. Fixed-film systems offer many advantages over suspended growth systems such as reduced operating costs, simplicity of operation, absence of sludge recycling problems, and compactness. The control of nutrient discharges to water bodies, improves water quality, fish production, and allow water reuse. The main objective of this study was to develop a fundamental understanding of the effect of CD on the transformations of nutrients in fixed-film biofilter systems subjected to alternating aeration I no-aeration cycles A fixed-film biofilter system consisting of three up-flow biofilters connected in series was developed and tested. The first and third biofilters were operated in a cyclic mode in which the biomass was subjected to aeration/no-aeration cycles. The influent wastewater was simulated aquaculture whose composition was based on actual water quality parameters of aquacuture wastewater from a prawn grow-out facility. The influent contained 8.5 - 9:3 mg!L a111monia-N, 8.5- 8.7 mg/L phosphate-P, and 45- 50 mg!L acetate. Two independent studies were conducted at two biofiltration rates to evaluate and confirm the effect of CD on nutrient transformations in the biofilter system for application in aquaculture: A third study was conducted to enhance denitrification in the system using an external carbon- source at a rate varying from 0-24 ml/min. The CD was varied in the range of0.25- 120 hours for the first two studies and fixed at 12 hours for the third study. This study identified the CD as an important process control parameter that can be used to optimise the performance of full-scale fixed-film systems for BNR which represents a novel contribution in this field of research. The CD resulted in environmental conditions that inhibited or enhanced nutrient transformations. The effect of CD on BNR in fixed-film systems in terms of phosphorus biomass saturation and depletion has been established. Short CDs did not permit the establishment of anaerobic activity in the un-aerated biofilter and, thus, inhibited phosphorus release. Long CDs resulted in extended anaerobic activity and, thus, resulted in active phosphorus release. Long CDs, however, resulted in depleting the biomass phosphorus reservoir in the releasing biofilter and saturating the biomass phosphorus reservoir in the up-taking biofilter in the cycle. This phosphorus biomass saturation/depletion phenomenon imposes a practical limit on how short or long the CD can be. The length of the CD should be somewhere just before saturation or depletion occur and for the system tested, the optimal CD was 12 hours for the biofiltration rates tested. The system achieved limited net phosphorus removal due to the limited sludge wasting and lack of external carbon supply during phosphorus uptake. The phosphorus saturation and depletion reflected the need to extract phosphorus from the phosphorus-rich micro-organisms, for example, through back-washing. The major challenges of achieving phosphorus removal in the system included: (I) overcoming the deterioration in the performance of the system during the transition period following the start of each new cycle; and (2) wasting excess phosphorus-saturated biomass following the aeration cycle. Denitrification occurred in poorly aerated sections of the third biofilter and generally declined as the CD increased and as the time progressed in the individual cycle. Denitrification and phosphorus uptake were supplied by an internal organic carbon source, and the addition of an external carbon source (acetate) to the third biofilter resulted in improved denitrification efficiency in the system from 18.4 without supplemental carbon to 88.7% when the carbon dose reached 24 mL/min The removal of TOC and nitrification improved as the CD increased, as a result of the reduction in the frequency of transition periods between the cycles. A conceptual design of an effective fixed-film BNR biofilter system for the treatment of the influent simulated aquaculture wastewater was proposed based on the findings of the study.

The role of the health surveillance program in the Queensland coal mining industry

The Queensland Coal Industry Employees Health Scheme was implemented in 1993 to provide health surveillance for all Queensland coal industry workers. Tt1e government, mining employers and mining unions agreed that the scheme should operate for seven years. At the expiry of the scheme, an assessment of the contribution of health surveillance to meet coal industry needs would be an essential part of determining a future health surveillance program. This research project has analysed the data made available between 1993 and 1998. All current coal industry employees have had at least one health assessment. The project examined how the centralised nature of the Health Scheme benefits industry by identi~)jng key health issues and exploring their dimensions on a scale not possible by corporate based health surveillance programs. There is a body of evidence that indicates that health awareness - on the scale of the individual, the work group and the industry is not a part of the mining industry culture. There is also growing evidence that there is a need for this culture to change and that some change is in progress. One element of this changing culture is a growth in the interest by the individual and the community in information on health status and benchmarks that are reasonably attainable. This interest opens the way for health education which contains personal, community and occupational elements. An important element of such education is the data on mine site health status. This project examined the role of health surveillance in the coal mining industry as a tool for generating the necessary information to promote an interest in health awareness. The Health Scheme Database provides the material for the bulk of the analysis of this project. After a preliminary scan of the data set, more detailed analysis was undertaken on key health and related safety issues that include respiratory disorders, hearing loss and high blood pressure. The data set facilitates control for confounding factors such as age and smoking status. Mines can be benchmarked to identify those mines with effective health management and those with particular challenges. While the study has confirmed the very low prevalence of restrictive airway disease such as pneu"moconiosis, it has demonstrated a need to examine in detail the emergence of obstructive airway disease such as bronchitis and emphysema which may be a consequence of the increasing use of high dust longwall technology. The power of the Health Database's electronic data management is demonstrated by linking the health data to other data sets such as injury data that is collected by the Department of l\1mes and Energy. The analysis examines serious strain -sprain injuries and has identified a marked difference between the underground and open cut sectors of the industry. The analysis also considers productivity and OHS data to examine the extent to which there is correlation between any pairs ofJpese and previously analysed health parameters. This project has demonstrated that the current structure of the Coal Industry Employees Health Scheme has largely delivered to mines and effective health screening process. At the same time, the centralised nature of data collection and analysis has provided to the mines, the unions and the government substantial statistical cross-sectional data upon which strategies to more effectively manage health and relates safety issues can be based.