Brain trauma occurs frequently in children and its consequences cause significant health and financial burden to the patients, their carers and society. This thesis assessed the modulating effects of physiological, genetic, and biochemical factors on the sequelae of childhood brain trauma. Primary brain injury from the mechanical forces of trauma and secondary brain insults consequent on the primary injury are determinants of brain trauma outcome. The most important secondary insults recognised are reduced cerebral perfusion pressure (CPP) and raised intracranial pressure (ICP). CPP is governed by the mean arterial blood pressure and the ICP. During childhood these physiological measures change with age. With continuous physiological recordings, ‘critical’ age-related minimum CPP thresholds for children aged 2-6, 7-10 and 11-15 years were defined as 48, 54 and 58mmHg respectively. Utilising these thresholds and a novel cumulative pressure-time index (PTIc), we have demonstrated that CPP insult still remains a feature in 80% of the severe brain trauma patients and significantly relates to global outcome. Brain trauma and cerebral ischaemia are stimuli to the inflammatory cascade leading to further brain damage. Serum adhesion molecule levels after brain trauma indicate injury severity and predict outcome better than brain specific proteins. Predictability is improved using more than one serum biomarker level. Neuro-inflammatory pathways involving adhesion molecules may have a strong modulating effect on brain trauma outcome but warrants further investigations in relation to CPP insult. Genetic factors such as Apolipoprotein E (APO E) genetic polymorphisms may additionally influence outcome, but it was not known whether genetic factors lessen the quantity of CPP insult or the cellular response to it. We demonstrated that the e4 carriers who had unfavourable outcome had 22 times less CPP insult than the non-e4 carriers, while the e3 homozygous who had good recovery had 26 times more CPP insult than the non-e3 homozygous. This suggests that APO E polymorphisms may affect the patient’s cerebral ischaemic tolerance differently, indicating especially the need to prevent CPP insult among e4 carriers. Cerebral ischaemia may, therefore, be a common pathway through which physiological and genetic factors modulate outcome after brain trauma.

A field survey was conducted following the Deepwater Horizon blowout and it was noted that resulting coastal petroleum deposits possessed distinct geometries, ranging from small tar balls to expansive horizontal oil sheets. A laboratory study evaluated the effect of oil deposit geometry on localized gradients of electron acceptors and microbial community composition, factors that are critical to accurately estimating biodegradation rates. One-dimensional top-flow sand columns with 12-hour simulated tidal cycles compared two contrasting geometries (isolated tar "balls" versus horizontal "sheets") relative to an oil-free control. Significant differences in the effluent dissolved oxygen and sulfate concentrations were noted among the columns, indicating presence of anaerobic zones in the oiled columns, particularly in the sheet condition. Furthermore, quantification of genetic markers of electron acceptor and catabolic conditions via quantitative polymerase chain reaction of dsrA (sulfate-reduction), mcrA (methanogenesis), and cat23 (oxygenation of aromatics) genes in column cores suggested more extensive anaerobic conditions induced by the sheet relative to the ball geometry. Denaturing gradient gel electrophoresis similarly revealed that distinct gradients of bacterial communities established in response to the different geometries. Thus, petroleum deposit geometry impacts local redox and microbial characteristics and may be a key factor for advancing attenuation models and prioritizing cleanup. / Master of Science