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Spinal cord injury (SCI) is a complex medical condition with multiple sequelae. The level and severity of a lesion will determine the degree of disability and associated co- morbidities, the most obvious of which is paralysis. Other concomitant issues, such as muscle contractures, poor seated posture and fear of falling, can also lead to a reduced quality of life. Although there is currently no cure for SCI, many of the comorbidities can be managed or mitigated through technology and physical rehabilitation practices. The aim of this thesis was to inform spinal cord injury (SCI) mobility rehabilitation, focusing on postural control and upright stepping using robotic assisted gait training (RAGT). A systematic review investigating RAGT use in SCI concluded that although RAGT has the potential to benefit upright locomotion of SCI individuals, it should not replace other therapies but should be incorporated into a multi-modality rehabilitation approach. Seated postural control, upper-body posture and fear-of-falling in SCI individuals were also explored. Stability performance and control demand were compared between high- and low-level injury groups as was fear-of-falling. An individualised limit of stability boundary (LOS) facilitated the differentiation between high- and low-level injuries during static tasks; however, its use during dynamic tasks was limited and potentially influenced by fear-of-falling. Few studies have quantified the user's motion inside a lower limb robotic exoskeleton (LEXO), and none have reported marker placement repeatability. Standard error of measurement was reported for three-dimensional trunk and pelvic orientations and hip, knee and ankle angles in the sagittal plane during level walking. This revealed the marker set and placement to produce good levels of agreement between visits, with most values falling between the accepted standard of 2-5o. These findings indicated that the marker placement was repeatable and could be used in the subsequent chapters involving motion capture of overground walking. Three-dimensional gait parameters of able-bodied individuals walking with and without a LEXO at two speeds (comfortable (CMBL) and speed-matched (SLOW) to the LEXO) were investigated. Statistical parametric mapping revealed significantly different waveforms at the ANOVA level for all kinematic variables, however minimal differences in sagittal plane lower limb kinematics were identified between LEXO and SLOW gait, suggesting LEXO gait resembled slow walking when speed-matched. Altered kinematics of the pelvis and trunk during LEXO use suggest that overground exoskeletons may provide a training environment benefiting postural control training. Finally, the biomechanical characteristics of able-bodied and SCI users walking in an overground LEXO were investigated. Variables associated with neuroplasticity in SCI (hip extension and lower limb un-loading) were not significantly different between groups, indicating that afferent stimuli to facilitate neuroplastic adaptations in individuals with a SCI can be generated during LEXO gait. Upper-body orientation facilitated stepping and maintained balance, thereby requiring the participant's active involvement. This thesis has provided evidence that LEXOs can deliver appropriate stimuli for upright stepping and that upper-body engagement can facilitate postural control training, potentially leading to improved seated postural control.

Chronic rhinosinusitis (CRS) with or without nasal polyps (NP) affects up to 15% of the UK population significantly affecting quality of life and impacting heavily on health care resources. Despite millions of pounds spent on research each year, the underlying cause of CRS remains unknown. Bacteria have been implicated in playing a role in mediating the ongoing inflammation in CRS. Bacteria possess the ability to quickly adapt to environmental changes, readily interchanging between planktonic, biofilm and intracellular profiles. Emerging evidence suggests that CRS is the result of a locally dysregulated innate immune system caused by changes in bacterial profiles in a bid for survival. The work presented in this thesis aimed to clarify this proposed theory through characterisation of bacterial profiles in CRS and analysis of the effect on the local innate immune system at a cellular level. A prospective study was performed using ex-vivo sinonasal mucosal and NP tissue from CRS patients, and sinonasal mucosa from non-CRS patients undergoing transsphenoidal pituitary surgery as a control. Tissue was analysed using the LIVE/DEAD® BacLight™ viability kit, fluorescent in situ hybridisation, scanning electron microscopy, transmission electron microscopy, confocal laser scanning microscopy and immunohistochemistry. An explant tissue model was developed to explore histological changes at the host-environment interface after addition of exogenous Staphylococcus aureus (S aureus) and Staphylococcus enterotoxin B (SEB). An in vitro cell culture model was developed to investigate cellular changes resulting from mast cell-S aureus interactions. Surface-related biofilms were identified on CRS sinonasal mucosa. S aureus was the commonest microbe identified. Sodium nitroprusside appeared to have little or no effect on dispersal of surface-related CRS biofilms. In NP, bacteria were sub-epithelial and within mast cells (intracellular). This is the first reported study to observe intracellular S aureus within mast cells in NP. The presence of SEB significantly increased the internalisation of S aureus into mast cells. S aureus entered mast cells through phagocytosis and via extracellular traps. Proliferating intracellular S aureus led to mast cell expansion and eventual rupture, seeding viable S aureus and proinflammatory mediators into the extracellular space. These findings demonstrate the ability of S aureus in CRS to manipulate the host's innate immune system in order to facilitate survival. Adaptation of bacteria into different profiles results in different pathophysiological effects. The intermittent dispersal of active planktonic bacteria from surface-related bacterial biofilms on nonpolypoidal mucosa mediates the ongoing chronic inflammation and symptom relapse in CRS. Intracellular S aureus within mast cells could act as a reservoir for bacteria constantly seeding into the extracellular environment leading to the build-up of proinflammatory cytokines and mediators, thus promoting tissue oedema and potentially nasal polyp growth. These findings suggest that NP formation may be an indirect consequence of a S aureus survival strategy to evade host defences.