Modelling the effectiveness of grass buffer strips in managing muddy floods under a changing climate

Muddy floods occur when rainfall generates runoff on agricultural land, detaching and transporting sediment into the surrounding natural and built environment. In the Belgian Loess Belt, muddy floods occur regularly and lead to considerable economic costs associated with damage to property and infrastructure. Mitigation measures designed to manage the problem have been tested in a pilot area within Flanders and were found to be cost-effective within three years. This study assesses whether these mitigation measures will remain effective under a changing climate. To test this, the Water Erosion Prediction Project (WEPP) model was used to examine muddy flooding diagnostics (precipitation, runoff, soil loss and sediment yield) for a case study hillslope in Flanders where grass buffer strips are currently used as a mitigation measure. The model was run for present day conditions and then under 33 future site-specific climate scenarios. These future scenarios were generated from three earth system models driven by four representative concentration pathways and downscaled using quantile mapping and the weather generator CLIGEN. Results reveal that under the majority of future scenarios, muddy flooding diagnostics are projected to increase, mostly as a consequence of large scale precipitation events rather than mean changes. The magnitude of muddy flood events for a given return period is also generally projected to increase. These findings indicate that present day mitigation measures may have a reduced capacity to manage muddy flooding given the changes imposed by a warming climate with an enhanced hydrological cycle. Revisions to the design of existing mitigation measures within existing policy frameworks are considered the most effective way to account for the impacts of climate change in future mitigation planning. 

Modelling responses to spatially fractionated radiation fields using preclinical image-guided radiotherapy

OBJECTIVES: Radiotherapy is planned to achieve the optimal physical dose distribution to the target tumour volume whilst minimising dose to the surrounding normal tissue. Recent in vitro experimental evidence has demonstrated an important role for intercellular communication in radiobiological responses following non-uniform exposures. This study aimed to model the impact of these effects in the context of techniques involving highly modulated radiation fields or spatially fractionated treatments such as GRID therapy.

METHODS: Using the small animal radiotherapy research platform (SARRP) as a key enabling technology to deliver precision imaged-guided radiotherapy, it is possible to achieve spatially modulated dose distributions that model typical clinical scenarios. In this work, we planned uniform and spatially fractionated dose distributions using multiple isocentres with beam sizes of 0.5 - 5 mm to obtain 50% volume coverage in a subcutaneous murine tumour model, and applied a model of cellular response that incorporates intercellular communication to assess the potential impact of signalling effects with different ranges.

RESULTS: Models of GRID treatment plans which incorporate intercellular signalling showed increased cell killing within the low dose region. This results in an increase in the Equivalent Uniform Dose (EUD) for GRID exposures compared to standard models, with some GRID exposures being predicted to be more effective than uniform delivery of the same physical dose.

CONCLUSIONS: This study demonstrates the potential impact of radiation induced signalling on tumour cell response for spatially fractionated therapies and identifies key experiments to validate this model and quantify these effects in vivo.

ADVANCES IN KNOWLEDGE: This study highlights the unique opportunities now possible using advanced preclinical techniques to develop a foundation for biophysical optimisation in radiotherapy treatment planning.

Outlier effects on robust joint modelling of longitudinal and survival data

Robust joint modelling is an emerging field of research. Through the advancements in electronic patient healthcare records, the popularly of joint modelling approaches has grown rapidly in recent years providing simultaneous analysis of longitudinal and survival data. This research advances previous work through the development of a novel robust joint modelling methodology for one of the most common types of standard joint models, that which links a linear mixed model with a Cox proportional hazards model. Through t-distributional assumptions, longitudinal outliers are accommodated with their detrimental impact being down weighed and thus providing more efficient and reliable estimates. The robust joint modelling technique and its major benefits are showcased through the analysis of Northern Irish end stage renal disease patients. With an ageing population and growing prevalence of chronic kidney disease within the United Kingdom, there is a pressing demand to investigate the detrimental relationship between the changing haemoglobin levels of haemodialysis patients and their survival. As outliers within the NI renal data were found to have significantly worse survival, identification of outlying individuals through robust joint modelling may aid nephrologists to improve patient's survival. A simulation study was also undertaken to explore the difference between robust and standard joint models in the presence of increasing proportions and extremity of longitudinal outliers. More efficient and reliable estimates were obtained by robust joint models with increasing contrast between the robust and standard joint models when a greater proportion of more extreme outliers are present. Through illustration of the gains in efficiency and reliability of parameters when outliers exist, the potential of robust joint modelling is evident. The research presented in this thesis highlights the benefits and stresses the need to utilise a more robust approach to joint modelling in the presence of longitudinal outliers.