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Non-invasive ventilation (NIV) is an evidenced based treatment of alveolar hypoventilation in patients with hypercapnic respiratory failure (HRF). Volume assured pressure support (VAPS) is a new mode of NIV that aims to maintain alveolar ventilation (VA) by autotitration of the pressure support (PS) delivered to a patient in response to changes in respiratory physiology. The overall aim of this thesis was to investigate the use of VAPS ventilation in patients with chronic HRF during wakefulness and sleep, specifically in the detection and treatment of acute exacerbations. Specific aims were to: a) determine if VA was maintained during VAPS ventilation in patients, with obstructive and restrictive pathologies, specifically during during exacerbations, and sleep (Chapters 3 and 4). b) determine the mechanism(s) of presumed maintenance of VA (Chapters 3 and 4). c) determine whether changes in the ventilator-measured respiratory parameters can be used to identify or predict exacerbations (Chapter 3). d) determine if VAPS can be used clinically to treat ventilatory failure as effectively as standard PS NIV in acute hypercapnic exacerbations of chronic respiratory disease, and in patients naive to NIV therapy (Chapters 5 and 6). I have concluded that VAPS ventilation provides an alternative ventilatory mode to standard PS ventilation, and can effectively maintain VA during sleep, and during exacerbations, when lung characteristics are changing. The mechanism of VA maintenance is likely to be the integration of complex patient-ventilator interactions, with large variability between patients, independent of diagnosis. Further studies of patient-ventilator interaction and its impact on the target ventilation may be aided by measuring respiratory drive or diaphragm work. Changes in ventilator-measured parameters were not predictive of impending exacerbation. Clustering may help to understand the physiological characteristics of exacerbations and individual ventilatory responses, and also to determine whether an autotitrating iVAPS improves outcomes of exacerbations, including survival.

The use of instructional multimedia, particularly video, within education is steadily increasing although the evidence-base regarding its usage typically only indicates that it is equivalent to or as effective as live demonstration or traditional teaching methods. The current study undertook a longitudinal quasi-experimental crossover study, over three consecutive academic years to evaluate the efficacy of instructional video to teach cognitive, affective and psychomotor skills to level 5 undergraduate sports therapy students. Through the use of a crossover design students undertook both the video and control conditions, they were assessed formatively on a weekly basis to provide a consistent measure of performance throughout the eighteen weeks of data collection within each year. The instructional videos used within the study were based upon (as far as possible) the multimedia principles proposed by Mayer to reduce extraneous cognitive load and maximise essential intrinsic and germane cognitive load. The results from the study were analysed with the use of effect size statistics and interpreted though the use of magnitude based inferences, an emerging alternative to the traditional use of null hypothesis testing. The findings of the study indicate that the use of the instructional videos was beneficial to the vast majority of the students, which builds upon the current evidence-base as it demonstrates that they can be used to enhance academic practice rather than be used as an equivalent resource.

Clinical reasoning is essential for effective physiotherapy practice, but its complexity makes it difficult to teach and learn. The literature suggests it is learnt within the practice environment and improves with patient-centred experience. However, physiotherapy education has a diminishing availability of practice-based learning. Patient simulation is used within medicine to counteract the decline in practice-based learning and to ease the theory-practice gap. This thesis explores the use of patient simulation to ease the theory-practice gap within physiotherapy. The literature relating to clinical reasoning, technology enhanced learning, simulation and virtual patients was reviewed. An institutional focus study was undertaken which explored the implementation of technology enhanced learning in physiotherapy education and detailed the development of a virtual patient simulation. A case study approach was used to explore the usability of virtual patient simulation to facilitate clinical reasoning and ease the theory-practice gap. Twenty-six physiotherapy students participated. Three virtual patients were made available for three months for self-directed learning. Data was collected using focus groups and the think-aloud method was employed to capture the verbalised thought processes of nine participants while assessing a virtual patient. This was supported by electronic data capture methods within the virtual patient software. Thematic analysis was used to interpret the qualitative data sets. Findings showed the fidelity of virtual patients facilitated clinical reasoning and eased the theory-practice gap. Participants perceived the virtual patient concept had merit and should be used in peer learning as part of their curriculum. Usability issues were identified and improvements suggested The think-aloud method revealed the value of educators supervising physiotherapy students verbalise their clinical reasoning, to identify errors and improve learning.

The intent of external beam radiotherapy is to deliver as high a radiation dose as possible to tumour volume whilst minimizing the dose to surrounding normal tissues. Recent development of techniques such as intensity modulated radiation therapy (IMRT) and stereotactic ablative body radiotherapy (SABR) aim to extend this capability. The main feature of these techniques is to use beams which often contain small fields and very steep dose gradients. These present several dosimetric challenges including loss of charge particle equilibrium (CPE), partial occlusion of the direct-beam source and steep fall-off in dose in the penumbra. Dosimeters which are small in size relative to the radiation field dimensions are recommended for such conditions. The particular glass beads studied herein have several potentially favourable physical characteristics; they are small in size (1 to 3 mm diameter), chemically inert, inexpensive, readily available and reusable. The dosimetric characterisation of glass beads has been obtained by irradiating them in various radiotherapy beams of kilo-voltage and mega-voltage photons, megavoltage electrons, protons and carbon ions. They exhibit minimal fading compared with commercial LiF thermo-luminescent (TL) dosimeters, have high TL light transparency, high sensitivity and a large dynamic dose range that remains linear from 1 cGy to 100 Gy They have also been shown to be independent of dose rate and beam incidence angle, as well as having a low variation in response with energy over a range of megavoltage photon and electron beams. The latter characteristic is of importance, where spectral changes may occur as a function of field size and off axis location and for the use of dosimeters in postal audit situations where each institution may have slightly different quality index (QI) for their respective photon energies thus ensuring that the calibration is still valid. These properties suggest their practical use as TL dosimeters for radiotherapy dosimetry. Investigations have been performed to evaluate the feasibility of using glass beads in treatment plan verification, small field radiation dosimetry and postal dosimetry audit.

Background: A rise in life expectancy has increased the likelihood of complex co-morbidities and disability resulting in a change in the make-up of hospitalised older adults and their rehabilitative requirements, including physiotherapy. Studies to date of the impact of physiotherapy on older adults admitted to hospital have investigated the intervention in isolation from context and have resulted in inconsistent outcomes. There remains a lack of evidence and theory regarding why physiotherapy is effective in some instances and not in others. Purpose: The thesis aims to examine the mechanisms might or might not work for patients, the influence of context on the actions of stakeholders to impact on outcomes and finally the appropriate methodology with which to investigate physiotherapy intervention. Method: Realistic evaluation (RE) was used as a framework for the study. Initial theories about the impact of physiotherapy on medically unwell older adults were expressed terms of context-mechanism-outcomes configurations and developed into hypotheses with stakeholders. Testing of hypotheses utilised a sequential mixed methods design including quantitative and qualitative measures, obtained from a convenience sample of older medically unwell patients (n=75) and a purposive sample of physiotherapists (n=6), patients and carers (n=8) respectively. Outcomes included measures of physiotherapy intervention, patient health status and hospital performance. Descriptive data analysis with subgroup comparison (frail/non-frail or cognitive impairment/cognitive impairment) was undertaken for outcome measures using Mann-Whitney U and Spearman’s correlation co-efficient. Qualitative data were analysed using framework analysis. Quantitative and qualitative study findings were reviewed, integrated and context-mechanism-outcome threads identified. Initial theories were refined in light of study outcomes. Findings: The sample mean age was 84.8 years (SD±7.1), 73% of individuals were identified as frail and 52% had cognitive impairment. Median hospital length of stay was 14 days (9-26). Median (IQR) physiotherapy interventions were 5 (3-10), total amount of physiotherapy 3.5 hours (1.8-7.21 hours) and frequency of physiotherapy intervention was 0.4 interventions/day (0.3-0.5). Subgroup analysis revealed patients had no between group differences in physiotherapy interventions. Moderate to large associations relating to a positive effect of physiotherapy on change in health status outcomes were present in unimpaired subgroups only. Physiotherapist and patient accounts indicated that organisational commitment to physiotherapy service provision, patient presentations of frailty and cognitive impairment and the priority of rehabilitation activities in the clinical ward setting triggered specific actions in frontline staff and patients. Patient and staff actions influenced by contextual factors affected the dose of physiotherapy and independent patient activity on the ward and contributed to explanation of patient health status outcomes in this study. Conclusion: The use of RE has resulted in the emergence of important elements related to context and stakeholder actions, which act as barriers or facilitators to physiotherapy implementation and effects of physiotherapy on medically unwell older adults admitted to hospital. Further testing of revised theories is required to enhance understanding of the impact of physiotherapy in terms of what works or doesn’t work for older adults. However, the in-depth knowledge revealed in this study has utility for informing models of physiotherapy and rehabilitation provision in the acute setting to best meet the needs of patients.

Radiotherapy is currently employed in the treatment of 50% of cancer patients. Cancer's heterogeneous nature mean optimal use of radiotherapy will be through combination and targeted therapies. Studies investigating the radiosensitising potential of solid gold nanoparticles have reported successful radiosensitisation only in combination with low kV radiation sources, but not with high kV or MV radiation. HGNs have been employed in photothermal ablation therapy, little work has been performed to investigate their potential as radiosensitisers, despite the superior physical properties, compared to solid AuNPs. The aims of this study were to investigate the radiosensitising potential of solid AuNPs and HGNs in combination with kV external beam radiation (XBR) and high kV β and γ radiation from ¹³¹I, from [¹³¹I]-MIBG. The study then aimed to investigate the effect of solid gold nanoparticles (AuNPs), hollow gold nanoparticles (HGNs), XBR and [¹³¹I]-MIBG alone and in combination on the growth of 3D MTS models. Radiosensitisation was measured by a decrease in clonogenic cell survival and quantified using the linear quadratic model. Association of radiosensitisation with changes in the cell cycle, dynamics of DNA double strand break (DSB) formation and repair and apoptotic cell death was assessed. The growth of spheroids was examined by assessing changes in spheroid volume. Significant radiosensitisation was observed in UVW/NAT and SK-N-BE cells, when solid AuNPs and HGNs were combined with [¹³¹I]-MIBG which was associated with an increase in DNA DSB formation. Solid AuNPs in combination with XBR induced minimal radiosensitisation, compared to significant radiosensitisation observed with HGNs. Solid AuNPs and HGNs alone and in combination with XBR and [¹³¹I]-MIBG had no significant effect on the growth of multicellular tumour spheroids (MTS), whereas exposure to XBR and [¹³¹I]-MIBG induced a dose dependant decrease in spheroid growth.

Electronic assistive technology (EAT) is prescribed by different professionals. Little is known regarding how these professionals make prescription decisions or their perceptions of their specialist knowledge and role in the assessment process. Study Aims: • to explore the participants’ perceptions of their specialist knowledge and role (Study 1); • to investigate the similarities and differences in the content and process of clinical decision making (CDM) during assessment and prescription of EAT for adults with an acquired brain injury (Study 2). Design: A cross-sectional design employing concurrent think-aloud method and semi-structured interviews. Methods: Two standardised case scenarios were presented to participants asked to think aloud their assessment of the patient (Study 2). A semi-structured interview followed (Study 1). Verbal data underwent thematic and analytic coding. The analytic coding underwent statistical analysis to explore the usage differences of the decision making processes between the professions. Decision process graphs (DPG) were drawn to explore whether there were patterns of use of the CDM processes according to level of expertise. Subjects: A purposive sample of 60 participants (BE, n=20; OT, n=20; SLT n=20) from assistive technology centres and brain injury units across England. Results: The CDM content was similar across the professions. The hypothetico-deductive model of decision making was used and two further stages, “cue implication” and “hypothesis implementation” emerged from the data. Patterns were observed in the DPG, which may be associated with differences in the CDM process according to levels of expertise. Participants’ reported profession-specific differences in their specialist knowledge and role, which were not clearly evident from the Study 2 results. Conclusions: The content and process of clinical decision making was similar across the three professions, though profession-specific specialist knowledge and role differences were reported by the participants. Level of expertise may affect the CDM process but did not affect the final prescription.

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Using Francis and Bessant (2005)'s concept of positional innovation, this thesis investigates how the natural environment is positioned as a health and well-being resource, and in addition how this can apply to market creation. The thesis encompasses pilot data and two ethnographic case studies that were collected through semi-structured interviews, ethnographic interviews and ethnography. The research was sited primarily in Cornwall, UK but also a month long international comparison was made in a secondment to Finland. The data suggests that the natural environment is being positioned to replicate mental states used in treatment of specific conditions, e.g. the calmness of an estuary is used to facilitate and replicate meditative and mindfulness practises. The natural environment and activities chosen were mapped to the individuals under therapy in a highly specific manner. This then offers a vast range of possible therapies through the plethora of natural environments found in the UK. In addition, the thesis tested the application of Pierre Bourdieu's meta-theory of the general theory of economic practices as a means for describing the phenomena of Positional Innovation, as well as contributing to the literature on this topic. It was found that the general theory of economic practices was extremely effective at describing the health and well-being service innovation process, far more in the author's opinion than most other innovation theories. Which are more focused on larger, corporate organisations and are therefore of less use in a health related contexts.