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The optic tectum is the main visual processing area in zebrafish and is involved in a variety of visually-driven behaviours. A key question is how information about the visual environment is processed and integrated in order to generate guided behaviour. The aim of this study was to explore the response properties of tectal neurons, i.e., their preference for certain features of the visual input. To do this, I developed a custom set-up for calcium imaging and simultaneous visual stimulation in older zebrafish larvae, up to the age of 21 dpf. First, this set-up was employed to measure the spatial receptive fields of tectal neurons with small moving spots. Notably, the results suggested that receptive field development is not completed by 9 dpf as previously believed; instead, receptive field refinement continues beyond this age. The results also confirmed that receptive fields in the optic tectum were relatively large in older larvae. Based on this, I formulated the hypothesis that tectal neurons might process multiple local features simultaneously. To test how the optic tectum encodes local features, I used small, moving oriented bars and combinations of bars, i.e., angles. Tectal responses to these stimuli suggested that, not only does the optic tectum encode local features, but is also tuned to horizontal-oriented local stimuli. Finally, I used a set of moving stimuli, consisting of simple features (i.e., lines and angles) and a composite feature (i.e. square) to test how information about multiple local features was integrated by tectal neurons. The results indicated that local features are spatially integrated in a sublinear fashion. The outcomes of the work presented in this thesis add to our understanding of how visual information provided by the retina is processed within the optic tectum.

No description available.

No description available.

Congenital Heart Disease (CHD) is one of the main causes of infant mortality in the UK and United States. In 2011, 47% of infants born with CHD in the UK did not survive to their first birthday. Often forms of CHD require the implantation of conduits (tubes) to redirect the blood flow around the reconstructed anatomy in the early days of life. In all cases, these children will require review surgery, often several times to replace the implanted conduit as the child grows. Critically every review procedure carries with it an increased mortality risk. This project represents the first stage in the development of a conduit/ anastomosis technology, which will grow in response to the growing child, matching haemodynamic demand and eliminating the need for revision surgery. Two prototypes were designed and developed. Each using an active drive mechanism to expand a stainless steel expansion strip with the slow and controlled movement required for such an application. Each of the designs were silicone coated using custom designed injection moulding techniques ensuring biocompatibility. Power and control systems were designed for each iteration taking into account their expansion methods to achieve the desired expansion rate of 12mm to 20mm in diameter of the implantation period. Three consecutive implantation studies were carried out throughout the device's development. In the first study, the device was implanted into the right ventricle of a cadaveric pig to determine any potential impediments that would need to be addressed for implantation into live animal models. The second implantation was carried out on 6 piglets, successfully establishing CPB procedures The third implantation was successfully carried out on 3 piglets, 2 of which survived the duration of the testing, confirming a successful encapsulation method to ensure biocompatibility, however it appeared the device failed to expand due to power line breakdown.

Bruising is an injury commonly observed within suspect cases of assault or abuse, however their interpretation is purely visual. Although the biology of bruising is known, how a blunt impact initiates bruising and influences its severity is not understood. Furthermore, the standard method of documenting bruising with colour photography is known to have limitations which in turn influence the already subjective analysis of bruise age and severity. Following ethical approval, this research aimed to address these problems through characterisation of a standardised blunt impact which was delivered to 18 volunteers. The resulting bruise was then imaged using 3 different photography techniques (colour, cross polarised (CP) and infrared (IR)) to determine if colour photography could be improved upon, whilst colour patterns using the L*a*b* colour model were taken from both colour and CP images to determine whether a measured colour timeline could be created to aid bruise age determination. Results showed that although no photography technique held any significant advantage over any other, CP provided greater image contrast than colour photography whilst IR imaging produced a clearer image of bruising over the initial stages of bruise formation. Although a general trend was seen for the measured colour patterns, they could not be characteristically attributed to any group of people, thus no colour timeline could be produced. Impact results demonstrated a characteristic tissue response which was strongly influenced by anthropometric features. These features also appeared to influence the severity of resultant bruising observed. It was concluded that both the photography and colour pattern methods assessed may not be the most appropriate for future research, whilst the potential variability of bruise severity between individuals was successfully visualised Therefore to gain a complete understanding of bruising, a detailed approach which combines impact, tissue response and the resulting bruise appearance is required.

Background : Heart failure is one of the principal causes of death and disability. The causes of heart failure are many, and a number of technologies have been developed to address this issue by providing support to the failing heart, both as a permanent solution and as a bridge to recovery. These options are called Mechanical Circulatory Support Devices, a particular branch of these devices is the Ventricular Assist Devices, which have been under intense development over the recent years offering a promising solution for this major problem. However, these devices are still bulky, and heavy designed to support failing hearts in the adult population. On the other hand, little has been done in recent times on the development of implantable solutions for heart failure or insufficiency in children. There are many reasons for this, but primarily the relatively small number of children requiring these procedures, the challenges associated with growth, and the lack of physical space for such implantable circulatory support technologies in children are fundamental limitations to the development and deployment of these technologies. Aims of the project : The primary purpose of this project was to investigate the development of a new miniaturised self-power VAD that is suitable for paediatrics implantation. This project suggested the use of the newly developed Artificial Muscles to create a mesh that envelops the heart and works as an external assisting circulation mechanism. The same materials could be used to generate electricity when deformed, which can be used to power the proposed device. Critically, the project was to focus on optimising the materials with regard to their operating efficiency to ascertain whether they represent a viable option for VAD production. Materials and Methods : A full review of the current available Artificial Muscles was performed to choose the most suitable type for this project. Then different fabrication protocols were developed to make IPMC Artificial Muscles using platinum and palladium coatings. A series of characterization tests were conducted on the fabricated Ionic Polymeric Metal Composites (IPMC) to ensure their quality. Finally, the mechanical and electrical properties were tested and compared with the proposed device requirements. Results : The review of Artificial Muscles showed that IPMC would be the best candidate to use in this application. The characterisation tests showed as well that the produced IPMC Artificial Muscles were fabricated to the same standards as those commercially available, and the reported by other investigators. However, these materials showed very low mechanical output with high electrical power consumption, which made them far from practical and not suitable for the proposed application. On the other hand, IPMCs showed promising results as an option to generate electricity to power low consumption implantable devices.

Introduction: Osteoarthritis is one of the leading causes of disability, and the knee joint is the most commonly affected site in the body. The last resort for treatment of end-stage knee osteoarthritis is total knee arthroplasty surgery. Despite the plethora of implant designs, the current evidence on which bearings give the most natural movement and function is still scarce. Aims: the aim of this study was to compare the functional performance of fixed and mobile bearings, with different degrees of congruency. Methods: participants underwent 3D motion capture analysis during two activities of daily living. Patient participants were recorded before, four to six weeks after, and a year after the operation. Pain and satisfaction levels were also surveyed using bespoke questionnaires and the Oxford knee score. Participants’ functional performance was accessed by means of an innovative statistical procedure (i.e. hierarchical clustering), that fruitfully classified movement patterns, and discerned healthy from unhealthy movement behaviours. Results: osteoarthritic participants used different movement strategies compared to healthy individuals. Patient participants’ arm and feet behaviour was often categorised as asymmetrical, indicating the presence of compensation mechanisms due to weakness of the affected join. Post-operational behaviour tends to converge to the controls’ performance. No differences were observed due to knee implant allocation, or anthropometric characteristics. Questionnaire analysis revealed significant improvement post-operatively in the self-assessment of patient participants, but with no eminent correlation between implant design and outcome measures. Conclusion: the proposed hierarchical clustering procedure managed to adequately, rapidly and reliably evaluate changes in the movement habits of patients after total knee arthroplasty, and access their improvement throughout their rehabilitation process.

Hernia repairs are among the most common surgical procedures performed, with more than 20 million hernias estimated to be repaired every year around the world. Mesh insertion is the most common method of treatment, with the mesh typically being made from polypropylene (PP). Significant complications can arise from PP meshes that include chronic infection, inflammation and pain. Electrospinning, a technique that utilises electric forces to create micro- and nanofibres, was used to fabricate a new-generation of hernia mesh (drug-loaded polymeric mesh). Solutions of polycaprolactone (PCL) or polylactic acid (PLA), two aliphatic polymers commonly used in various clinical applications, were individually mixed with irgasan (IRG) (an antibacterial agent) or levofloxacin (LEVO) (a broad-spectrum antibiotic). Type I collagen was later included into the polymer-drug solutions in order to increase the biocompatibility of the samples. Electrospun samples were subsequently analysed for mechanical, physicochemical, drug release and biological characteristics. Electrospinning was useful in creating micro- and nano- fibres for polymer-drug combinations. IRG-loaded scaffolds displayed a sustained release behaviour, whilst LEVO-loaded scaffolds showed a burst release. The addition of type I collagen modified the release rate of PLA-LEVO scaffolds from burst to sustained release, and modified surface characteristics from hydrophilic to hydrophobic. Biological studies demonstrated smooth muscle cells affinity to LEVO-loaded scaffolds, with high adhesion and proliferation, whilst also demonstrating significant resistance to bacterial growth (E. coli and S. aureus).

Knee arthroplasty surgeries have become an increasingly common procedure in orthopaedics, especially for younger patients. New robotic technology has been introduced into the orthopaedic surgery with good results. The robotic technology is versatile to use and it then opens up the development of potential novel prosthetic designs. This project investigates one type of knee arthroplasty - the unicondylar knee arthroplasty (pseudonyms: unicondylar (or unicompartmental) knee arthroplasty (or replacement) abbreviated to UKA or UKR); and how it can be improved by robotic technology. The project followed a design process applying a range of methods to generate as many different prosthesis concepts, and then to organise and evaluate the concepts in a systematic manner. The strongest ideas were highlighted and, where possible, were developed into experiments. Some of the experiments were conducted practically in the lab while others were carried out by computer simulations. The project was able to provide constructive insight into novel prosthesis features and provide two prosthesis prototypes fashioned from the concepts. From the final two concepts, the BQ concept was picked due to the overall performance in the experimentation.