Neurological rehabilitation technologies such as Robot Therapy (RT) and noninvasive brain stimulation (NIBS) can promote motor recovery after stroke. The novelty of this research was to explore the feasibility and the effect of the combination method of NIBS called transcranial Direct Current Stimulation (tDCS) with uni-lateral and three-dimensional RT for the impaired upper limb (UL) in people with sub-acute and chronic stroke. This thesis involved three studies: (a) systematic review with meta-analyses (b) a pilot double-blinded randomised controlled trial with a feasibility component and (c) a reliability study of the measurement of Motor Evoked Potential (MEP) response using Transcranial Magnetic Stimulation in healthy adults. The first study involved a review of seven papers exploring the combination of tDCS with rehabilitation programmes for the UL in stroke. For the second study, stroke participants underwent 18 x one hour sessions of RT (Armeo®) over eight weeks during which they received 20 minutes real tDCS or sham tDCS. Outcome measures were applied at baseline, post-intervention and at three-month follow-up. The qualitative component explored the views and experiences of the participants of RT and NIBS using semi-structured interviews. The third study involved age-matched healthy adults exploring intrarater and test-retest reliability of the TMS assessment. Results of the three studies were the following: Seven papers were reviewed and a small effect size was found favouring real tDCS and rehabilitation programmes for the UL in stroke. 22 participants (12 sub-acute and 10 chronic) completed the pilot RCT. Participants adhered well to the treatment. One participant dropped out of the trial due to painful sensations and skin problems. The sub-acute and chronic groups showed a clinically significant improvement of 15.5% and 8.8% respectively in UL impairments at post-intervention from baseline. There was no difference in the effects of sham and anodal tDCS on UL impairments. Participants found the treatment beneficial and gave suggestions how to improve future research. In summary, the TMS assessment showed excellent reliability for measurement of resting motor threshold but poor to moderate reliability for MEP amplitude. In conclusion, it was indicated that RT may be of benefit in sub-acute and chronic stroke however, adding tDCS may not result in an additive effect on UL impairments and dexterity. The present study provided a power calculation for a larger RCT to be carried out in the future.

The ability to quantify kinematic parameters of the knee is crucial in understanding normal biomechanics, recognising the presence of pathology and its severity, planning treatment and evaluation of outcomes. Current methods of quantifying lower limb kinematics remain limited in allowing accurate dynamic assessment. Computer assisted surgery systems have been validated in quantifying kinematic parameters, but remain limited to the operative setting. Recently, image-free computer assisted surgery technology has been adapted for non-invasive use and validated in terms of repeatability in measuring coronal and sagittal femorotibial mechanical alignment in extension. The aim of this thesis was to develop and implement a set of validation protocols to quantify the reliability, precision and accuracy of this non-invasive technology in quantifying lower limb coronal and sagittal femorotibial mechanical alignment, anteroposterior and rotatory laxity of the knee by comparison with a validated, commercially available image-free computer assisted surgery system. Pilot study confirmed feasibility of further experimental work and revealed that the noninvasive method measured with satisfactory precision and accuracy: coronal mechanical femorotibial alignment (MFTA) from extension to 30° knee flexion, anteroposterior translation in extension and tibial rotatory laxity during flexion. Further experiments using 12 fresh cadaveric limbs revealed that the non-invasive method gave satisfactory precision and agreement with the invasive system measuring MFTA without stress from extension to 40° knee flexion, and with 15Nm coronal stress from extension to 30° knee flexion. Using 100N of anterior force on the tibia, the non-invasive system was acceptably precise and accurate in measuring sagittal tibial displacement from extension to 40° flexion. End of range apprehension, such as has been proven repeatable in measuring tibial rotatory laxity was used and the non-invasive method gave superior 3 precision and accuracy to most reported non-invasive devices in quantifying tibial rotatory range of motion. Non-invasive optical tracking systems provide a means to quantify important kinematic parameters in health and disease, and could allow standardisation of knee examination increasing communicability and translation of findings from the out-patient to operative setting. This technology therefore could allow restoration of individual specific kinematics in knee arthroplasty and soft-tissue reconstruction.

Non-compressible haemorrhage from within the torso and junctional regions constitutes the leading cause of potentially preventable death on the battlefield. It can be defined as haemorrhagic shock arising from injury to named torso vessels, pulmonary parenchyma, high grade solid organ injury and/or disruption of the bony pelvis. Data from the US Department of Defence Trauma Registry demonstrate a torso injury rate of 12.7% with 17.1% of casualties exhibiting torso injury and shock. The overall mortality is 18.7%, with major arterial injury and pulmonary injury identified as independent predictors of mortality on multivariate analysis. The UK Joint Theatre Trauma Registry reports similar findings with the greatest burden of mortality occurring prior to hospital admission (75.0%), a rate that has remained unchanged over a decade of war. Injury from improvised explosive devices (IEDs) in particular are associated with non-compressible haemorrhage, frequently causing traumatic lower extremity amputation in combination with torso injury. Contemporary surgical strategy relates to early operative haemorrhage control in patients presenting with shock. In patients sustaining a circulatory arrest, resuscitative thoracotomy and aortic cross clamping can be used to control inflow and increase cardiac afterload. The UK experience over 5 years at Camp Bastion demonstrated a mortality of 78.5%, with greatest survival observed in patients with the shortest time to thoracotomy. In patients sustaining lower extremity amputation following IED injury, 1 in 5 require a laparotomy for proximal vascular control, with less than half requiring further intra-abdominal intervention. There is a pressing need for a haemorrhage control and resuscitation adjunct in non-compressible haemorrhage that can be deployed prior to or as an adjunct to operative haemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a technique that can occlude the aorta without the need for an operating theatre. It is an experimental technique, so its effect on survival and physiology is unknown. In a porcine model of uncontrolled pelvic haemorrhage, infra-renal REBOA was shown to be as effective as chitosan gauze in the setting of normal coagulation. However, REBOA was associated with a significantly greater survival in a coagulopathic setting. Similar results were obtained when using a porcine model of abdominal haemorrhage in conjunction with thoracic REBOA. In both studies, balloon occlusion demonstrated a significant improvement in systolic blood pressure and other haemodynamic measures compared to the no-occlusion control groups. Having demonstrated a survival and haemodynamic benefit in uncontrolled haemorrhage models, the metabolic and inflammatory consequences of thoracic REBOA were characterised in further detail using a porcine model of controlled hypovolaemic shock. Occlusion for 30 and 90 minutes was associated with a significant lactate burden when compared to animals undergoing shock alone. However, following resuscitation with blood and intravenous fluid, normal physiology was restored within 6 hours. The inflammatory sequelae were studied following 30, 60 and 90 minutes of shock and occlusion. Increasing occlusion time resulted in an escalating release of interleukin-6 which manifest clinically as an increase in ARDS and need for vassopressor support. In order to develop a fluoroscopy free REBOA system, a series of human studies were undertaken to examine the relationship between an external measure of torso height and aortic length in order to guide insertion length. A retrospective examination of computed tomography in male trauma patients demonstrated a correlation between torso height and aortic length. This was confirmed by a prospective study which was also used linear regression to develop equations predictive of insertion length. Finally, the UK Joint Theatre Trauma Registry was used to determine the need for REBOA in a population of UK military personnel injured over 10 years of conflict. Of 1317 severely injured patients 70.2% had no indication, 11.2% had a contra-indication and 18.5% had an injury pattern indication for REBOA. Of those with an indication for REBOA, 66 (27.0%) patients died en-route to hospital and 29 (11.9%) died in-hospital. In conclusion, non-compressible haemorrhage constitutes a significant burden of potentially preventable battlefield mortality. REBOA is a technique that can be used in the thoracic or infra-renal aorta as a haemorrhage control and resuscitation adjunct, prior to operative haemorrhage control. While associated with a significant survival advantage in models of uncontrolled haemorrhage, it is associated with a significant metabolic penalty, although with resuscitation this can be ameliorated successfully.

Minimally invasive surgery (MIS) is fast becoming a preferred choice for patients and surgeons, due to its biological, aesthetic and commercial benefits. The dynamic hip screw (DHS) is the standard implant for the treatment of fractures of the proximal femur, which is considered to be the most frequent injury in the elderly. The aim of this research was to develop MIS for the treatment of these fractures utilising the principle and surgical technique of the DHS implant. During the research, a thorough medical device design process was conducted to develop three new medical devices 13 a new angle guide, a new ergonomic T-handle and a new implant. The design process for each of the new medical devices conformed to requirements of the relevant standards. The designs of the new medical devices were verified using methods such as risk analysis, finite element analysis and mechanical testing of manufactured prototype. Finally, an operative technique applying a minimally invasive approach with the new medical devices was developed to treat the fractures of the proximal femur.