Patello-femoral joint syndrome (PFJS) is a common problem that is challenging to treat. The dominant theory of its aetiology is „patellar malalignment‟, in which the vastus medialis oblique (VMO) muscle is ineffective in controlling patellar position but this is based on assumption. The Q-angle, a frontal plane measure, indicates patellar position relative to the pelvis and tibia; however, there is no standardised measurement protocol and it is assumed to be a fixed value. The work reported highlights the tension between measurement rigour and clinical utility. Valid measurement of the Q-angle and VMO muscle were established using: motion analysis, magnetic resonance imaging (MRI) and ultrasound imaging, in recreationally active healthy participants, then applied in various experiments involving people with PFJS, with the following conclusions: The Q-angle: * varied over 60 seconds in relaxed standing * exhibited differences in movement patterns of the three markers which form the Q-angle between healthy and PFJS groups during the stance phase of gait * was generally at its maximum at the beginning of the stance phase of gait and at its minimum at the end * did not correlate with pronation at the sub-talar joint VMO muscle size: * linear and CSA measures of the VMO muscle correlated well * measures of VMO muscle size from ultrasound were shown to be valid when compared with MRI and were equally reliable No correlation between the Q-angle and VMO muscle size was found. These results increase our understanding of the usefulness of the Q-angle, particularly its natural variation of between 30 and 40 in static standing and its different movement pattern during gait in PFJS. It was established that ultrasound imaging provides valid measures of VMO muscle size and the relationships between its CSA and linear dimensions were characterised.

The knee is a complex joint, prone to instability and damage, meaning a complicated architecture of soft tissues is necessary to ensure any stability of the joint. These structures are innervated, and play an important role in both proprioception, the sensing of a body’s own limb positions, and nociception, the sensing of painful stimuli. The purpose of this project has been to develop a computational model that can replicate the behaviour of the mechanical sensing nerve endings in the knee joint. An adapted Hodgkin-Huxley model has been developed and used to simulate the behaviour of the nerve endings. These models have been coupled with a three dimensional finite element model of a feline knee joint, which has been built with use of x-ray CT and MRI scans of a cat’s hind limb, allowing neural responses to be predicted as the position of the knee joint changes. Once the behaviour of the complete model has been verified, through comparisons with recordings of neural responses in the literature, it was possible to observe the effect of removing a soft tissue structure on the neural response. The anterior cruciate ligament (ACL) was removed from the model, and a series of tests run to determine the effect of ligament damage on neural response. It was predicted that removing the ACL from the knee joint can increase the neural responses to changes in knee position, agreeing with data in the literature. This could indicate an increase in pain at the joint, and could help with understanding the causes of pain and changes proprioception experienced by patients with damaged ACL.

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.

Over the last few years, there has been an increase in the clinical methods targeting the human tracheobronchial tree, both for therapeutic and diagnostic purposes. For these methods to be effective, a good understanding of the lung structure is necessary. This knowledge can be attained through the use of medical imaging protocols such as CT and MRI, and can in turn be used to predict aerosol deposition for particles employed for inhalation therapy via the simultaneous use of radionuclide imaging. However, due to limitations imposed by the technologies currently available, not enough information can be gathered in-vivo about the respiratory tract. Consequently, widespread use of anatomical models of the lung is being made by clinicians in order to enable them to fill this gap in information. The thesis is concerned with the improvement of such models and the introduction of new, more advanced ones in an effort to accurately describe the human lung using mathematical and physical principles. A method is developed for improving the Conceptual Model constructed in the Nuclear Medicine Department of Southampton General Hospital by incorporating to it real, patient-specific data obtained through CT imaging. A model of the bronchopulmonary segments of the lung is also created and an atlas that can be used for the identification of these sub-structures in any lung space is formed. An algorithm for the generation of a fully-descriptive 3D model of the airway tree is then designed and implemented, the morphometry of which is assessed to confirm that it is a realistic representation of the target organ. The deterministic algorithm reveals the 3D geometry and orientation of the lung airways, thus enabling aerosol deposition and flow-pattern studies to be performed in a comprehensive way in previously inaccessible regions of the lung.

No description available.

This thesis consists of an investigation of the current use of visual representations, and drawing in particular, when teaching and assessing within anatomy education in medical studies. Although we know a lot about teachers’ use of visual representations and increasingly drawing, especially in the context of science education, less is known about the use of those tools by educators in the anatomical domain. Drawing is not currently systematically being used within assessment in anatomy education in UK medical schools, and its potential in assessment has not been investigated in depth. Four studies were conducted to answer the research questions set for this thesis. The first study investigated the way in which the teaching staff understand the use of visual representations in teaching, learning and assessment in anatomy. To answer this, observations of seven anatomy demonstrators were conducted within Year 1 dissection sessions, and interviews were conducted with the same demonstrators. The second study employed a real-world experimental design to explore if students’ drawings reveal changes in their understanding after dissection. Drawings from 98 Year 1 medical students were analysed in a within-subject crossover design, where students in the first condition drew the exterior of the heart before dissection in Week 1 and drew the superior mediastinum after dissection in Week 2. The order was reversed for students in the second condition. All drawings were analysed for their content and form with an extensive coding scheme that was developed for this thesis, as the existing coding approaches towards drawings were judged as inappropriate. The third study investigated the use of drawing to reveal changes in understanding as the medical degree progresses. Drawings of the exterior of the heart from 46 Year 3 students were analysed and compared to drawings from the Year 1 students. Finally, the fourth study investigated the way in which anatomy demonstrators understand drawing in the assessment of anatomical knowledge; eight artefact-based interviews were conducted with anatomy demonstrators. The findings offer important insights into the way in which visual representations and drawing in particular are being used by anatomy demonstrators within anatomy education and their perspectives on the use of drawing in teaching, learning and assessment. A significant contribution is also made to the knowledge regarding the use of drawing to assess understanding in spatially intensive domains, such as the anatomical one. This thesis also contributes to our knowledge of dissection as a method of teaching anatomy and the need for drawing training within this domain. Finally, the scheme for drawing analysis that was developed, evaluated and employed in this thesis can be considered a methodological contribution to the approaches of analysing drawings in the current literature.

Monitoring blood perfusion and oxygenation changes is of vital importance and for this reason many different techniques have been developed over the decades. Photoplethysmography (PPG) is an optical technique that measures blood volume variations in vascular tissue and it is well known for its utilisation in pulse oximetry for the estimation of arterial blood oxygen saturation (SpO2). In pulse oximetry, mainly the pulsatile component of the signal (AC PPG) is used while the continuous DC component is mostly excluded. Near Infrared Spectroscopy (NIRS) is another optical technique that measures changes in the concentration of oxygenated (ΔHbO2), deoxygenated (ΔHHb), and total haemoglobin (ΔtHb) from the variations in light attenuations at different wavelengths. The main motivation of this research is to explore the capability of Photoplethysmography in assessing tissue perfusion and oxygenation similarly as NIRS. The hypothesis underlining this research is that the DC component of the PPG signal contains information on the overall absorbed light and this part of the PPG signal, acquired at least two wavelengths, may be used to obtain ΔHbO2, ΔHHb, and ΔtHb as performed in NIRS. Therefore, DC PPG attenuations may be related to haemoglobin concentrations by the modified Beer-Lambert law (MBLL). In order to investigate this, novel reflectance, custom-made PPG sensors and measurement systems, including advanced signal processing algorithms, have been developed for the acquisition and analysis of raw PPG signals (AC + DC) from different anatomical locations. Three in vivo studies on healthy volunteers were carried out in order to investigate if ΔHbO2, ΔHHb, and ΔtHb estimated from PPG could indicate changes in blood perfusion and oxygenation. The studies consisted of vascular occlusions on the forearm, negative bed tilting, and whole body cold exposure. Raw PPG signals were acquired from different locations such as the forearm, fingers, and forehead, whereas simultaneous NIRS signals were used as a reference. The results showed that ΔHbO2, ΔHHb, and ΔtHb could be effectively estimated from PPG signals. These parameters indicated the changes in blood volumes and/or oxygenation, whereas comparison with NIRS signals showed good levels of correlation and trending. These promising results showed that DC PPG signals could be used to monitor changes in blood perfusion and oxygenation, extending the range of applications of Photoplethysmography.

The differentiation of human endometrial stromal cells (HESCs) into specialised decidual cells prepares the endometrium for embryonic implantation. The biochemical and morphological transformation of these cells is highly temporally regulated in order to define a transient period of endometrial receptivity. Currently, the involvement of circadian machinery, and clock dependent pathways in this process are not fully understood. Firstly, analysis of circadian rhythms in HESCs revealed a consistent loss of oscillations in clock components upon decidualization. Down-regulation of Period 2 (PER2) expression, apparent in the early stages of differentiation, was shown to be sufficient to cause this aperiodicity. In turn, temporal suppression of PER2 expression was achieved via reduced CLOCK binding to a non-canonical Ebox enhancer in the PER2 promoter. RNA sequencing analysis upon premature PER2 knockdown revealed a disorganised decidual phenotype in which cell cycle and mitotic regulators were perturbed. As such, PER2 acts to uncouple the endometrium from circadian oscillations during decidualization. Secondly, the gene PRIP-1 was shown to be PER2 dependent in undifferentiated HESCs. Endometrial expression of PRIP-1 was induced and maintained upon decidualization by the post-ovulatory rise in progesterone. Analysis of Ca2+ fluxes demonstrated the ability of PRIP-1 to act as a chelator of IP3 signalling. Additionally, PRIP-1, via its regulation of the AKT pathway, is shown to be an anti-apoptotic regulator in decidual HESCs. Together, these results indicate PRIP-1 functions as a molecular switch in response to progesterone signalling. High PRIP-1 levels during differentiation enable AKT and IP3 mediated cell survival, whilst declining levels upon P4 withdrawal leads to decidual apoptosis. In summary, I provide a novel paradigm whereby both PER2 and PRIP-1 act to uncouple the endometrium from various signalling inputs, enabling an autonomous decidual response. Asynchrony in these pathways can lead to a cascade of events resulting in an array of adverse pregnancy complications.

Background: People with diabetes and peripheral neuropathy have been reported to show alterations in lower limb joint function compared to healthy non-diabetic people. Specifically the maximum angular movement available at certain joints can be reduced during static, non-weight bearing tasks. Limited joint range of motion has the potential to compromise balance and stability thereby increasing the risk of falling. It is unclear whether a reduction in the extent of movement available at the joints is reflected by a reduction in the amount of angular movement actually utilised during a functional task such as stair negotiation. The aim of this study was to determine if people with diabetes show reduced dynamic range of motion at the ankle, knee and hip joints during stair ascent and descent in comparison to controls. Falls risk during stair negotiation was calculated by measuring the degree of variability in dynamic joint range of motion. Methods: Data were generated from three groups: subjects with diabetes and peripheral neuropathy (DPN), diabetes without peripheral neuropathy (DM), and healthy controls (Ctl). The study was conducted in a gait laboratory using motion capture and related 3D software for analysis. Joint range of motion for the ankle, knee, and hip were captured during level walking, stair ascent, and descent. A seven step, bespoke staircase was fabricated for this purpose. Analysis of Variance (ANOVA) and Newman-Keuls tests were used to analyse the data. Results: Significantly reduced ankle range of motion, in the sagittal plane, was observed in the DPN group during stair ascent when compared to the controls. For stair descent, the DPN group demonstrated a significant increase in knee and hip ROM in the frontal plane, and also hip ROM in the transverse plane. No significant differences between the groups were identified for joint variability. Conclusions: People with DPN demonstrate alterations in dynamic range of motion at the lower limb joints during stair ascent and descent. The degree of angular movement utilised for both stair tasks was decreased at the ankle joint and this has the potential to undermine balance and stability. In contrast, angular movement at the knee and hip joints was increased in the frontal and transverse planes. This may compensate for impaired balance and stability by increasing the base of support to maintain balance and assist in foot clearance and placement. The specific combination of increased angular movement at the knee and hip may represent a compensatory stair gait strategy in response to reduced angular movement at the ankle joint.

Tendon injuries continue to be a financial burden on the health care system of many western countries, whilst also remaining common and a significant challenge within the orthopaedic discipline with no consensus of opinion on the best therapeutic regime to be employed. Many polymers have been investigated for use in tendon repair. A range of polymers have shown good integration with limited immune response. However, to date no implant has been capable of delivering the physical properties observed in native undamaged tendon. Many of the polymers implanted have resulted in re-rupture or reduced mechanical function. Therefore, improvements are required in the choice of polymer and mechanical properties of the polymer are required. One means of achieving such improvements is to utilise co-polymers such as PHBHHx, which have shown favourable elastic properties when the ratio of HHx to PHB has been increased. Therefore, a PHBHHx polymer based scaffold was investigated as a potential scaffold for tendon repair. Whilst, also investigating the potential of FGF-4, FGF-6 and FGF-8 to differentiate both human embryonic and mesenchymal stem cells towards a tenocyte-like lineage. Finally, an investigation into whether a controlled production of PHBHHx based nanoparticles could produce different nanoparticles sizes that can be predicted and result in differing release profiles. This may allow for the synthesis of size controlled nanoparticles capable of delivering differing drug concentrations and sustained release properties.