Photodynamic therapy (PDT) has been used as a clinical treatment since the early 1990s and utilizes a photosensitising drug (PS), molecular oxygen and light of a specific wavelength, (usually visible light below 700nm) to generate singlet oxygen and other reactive oxygen species which are highly cytotoxic. Originally used as a treatment for superficial skin cancer it is now emerging as a treatment for other forms of cancer such as head, neck, lung and prostate cancers. There are however, several limitations which have prevented PDT obtaining wide spread clinical use. For example currently approved PS drugs absorb light in the visible region limiting tissue depth penetration to a few mm rendering the treatment unsuitable for deep seated tumours. Secondly, PS molecules also tend to be hydrophobic and can aggregate in aqueous solutions, leading to a reduction in singlet oxygen production. The focus of this PhD seeks to take advantage of the photophysical properties of conventional cadmium selenide quantum dots (QDs) (chapter 3) and the relatively new carbon based nano material known as carbon quantum dots (CQDs) (chapter 4), to address some of the difficulties currently faced with the use of conventional PS drugs in PDT. This strategy shall involve the synthesis, in vitro and in vivo evaluation of suitable nano-particlePS conjugates. In addition to the synthesis of conjugates for PDT implications, microbubblesensitiser conjugates were also developed for use in sonodynamic therapy (SDT). SDT refers to the ultrasound dependent cytotoxic effect of certain compounds (sonosensitisers). Ultrasound having far superior tissue dept penetration than light, overcoming the major limitation of poor tissue depth penetration observed in PDT. However there are still some undesirable characteristics associated with SDT. The accumulation of sonosensitisers in healthy tissue has been one such drawback, as sonosentisers (SS) are generally also PS this can lead to photosensitivity of the skin. In order to achieve a greater degree of selectivity the use of microbubble-SS conjugates was investigated (chapter 5). Lipid based microbubbles (MBs) are currently approved for use as contrast agents in diagnostic ultrasound applications and have also been investigated as potential drug / gene delivery vehicles. In chapter 5 Rose Bengal, a well known SS, was covalently attached to the surface of a lipid coated MB. The overall objective of this strategy was to investigate the potential of this MB-SS conjugate as a therapeutic for highly targeted, minimally invasive treatment of deep seated tumours.

Introduction: Internship for physiotherapists is recognised as necessary and beneficial in preparing graduated students to enter the workforce at a desired level of proficiency. The training model should provide the intern with quality learning experiences in the real-world context to develop the necessary knowledge, skills, attitudes and behaviours that supports their transition to independent practice. Recent regulatory developments in Singapore have required that physiotherapy graduates undergo compulsory supervised practice before registration. My organization has launched the formal internship program recently to align with regulatory and administrative requirements. As a hospital leader, it is expedient that I conduct an action-oriented research to better understand and address the organisational issues surrounding clinical internship, an area that has not been fully explored in my organization and country. Understanding what successful learning or effective training looks is vital in providing an internship program that would optimally train interns or novice physiotherapists to be clinically competent and ready for professional practice. Objective: The research objective was to gain insights on what makes for an effective physiotherapy internship; to evaluate my organization's current internship program and to formulate actionable strategies that can be implemented to progressively improve our current program. Method: Different research methods were adopted in this action-oriented research. Based on a conceptual framework of the clinical learning environment theorised from existing literature, a survey questionnaire was designed to collect data from stakeholder groups on their perception of factors influencing the effectiveness of current internship program. Focus groups were conducted to obtain rich qualitative data and to draw insights on the lived experiences of stakeholder-participants. Subsequent discussion of results with influential leaders support the triangulation of data and the needed buy-in from them to effect recommended change actions to improve practice. Results: Six (6) major factors were found to influence the effectiveness of physiotherapy internship. These factors or themes that emerged from the data grounded in our practice were: coaching activity, intern (learner) factors, supervisor (teacher) factors, intern-supervisor relationship, environmental factors and program factors. The research found that intern-supervisor relationship was ranked most important in influencing the effectiveness of internship training by clinical supervisors, recent interns and the community of physiotherapists. The overall effectiveness of our current internship program was rated average by all stakeholder groups. Strategies to improve current internship were developed and assessed by physiotherapy leaders for their implementation ability. These improvement strategies include clear definitions and articulation of supervised practice (internship) and coaching practice, specific guidance for interns and supervisors in preparing for their roles and responsibilities, and recommendations for capacity and capability development. Conclusion: Through action research, I, the scholarly manager-leader, was able to collaboratively formulate actionable strategies with key physiotherapy leaders to make improvements to our internship program for physiotherapists. This research study has value-added both in informing and improving practice. The knowledge and insights gained serve the purposes of the local physiotherapy community in which it was carried out. The knowledge produced may also provide academic insights and concepts of social and organizational behaviour for the interests of the bigger research community.

Balance dysfunction and the resultant falls and injuries, loss of confidence, alterations to lifestyle and overall health costs are a major problem to older people in Australia. The magnitude of these problems highlights the need for improved identification of those who may be at risk of falls, and for evaluation of the effectiveness of management programs which target both these individuals, and those who have established balance dysfunction. At the commencement of these studies, there was a need for validation or modification of several key balance related measures. These are reviewed in Chapter 2. The Chattecx Balance System was selected as a tool to measure postural stability under both static and dynamic conditions. Retest reliability of the test protocol on the Chattecx Balance System was evaluated in a group of healthy older women tested at weekly intervals. Intraclass Correlation Coefficients (ICC’s) were high for the dynamic test conditions (ICC>0.81), but poor for static test conditions (ICC<0.55). A learning effect was evident, necessitating the incorporation of a practice session on the Chattecx Balance System before formal measurements were undertaken. In addition the Nicholas Manual Muscle Tester, a hand held dynamometer used to evaluate leg muscle strength, was found to have acceptable levels of retest reliability.

Shoulder Impingement Syndrome is prevalent in sportsmen and can end sporting careers. The Acromio-Humeral distance (AHD) is a measure taken with ultrasound (US) and used to quantify the space in which structures in the shoulder become impinged. This space is normally reduced as the arm elevates. Factors identified in the literature that could further reduce this space, are explored in this thesis. Correlation analysis between factors (Scapula rotation in the coronal plane, Pectoralis Minor length, Thoracic kyphosis, Glenohumeral rotation and load) with the AHD was done to confirm or refute some of these associations. To accomplish the research: a) reliability of tools and stability of the measure was established; b) data was collected in elite sportsmen and controls to verify variance in the independent variables; c) correlation analysis between independent variables and the AHD was carried out to determine association. In summary, the results of this thesis demonstrated that factors influencing the Acromio-Humeral distance are multifactorial, including Pectoralis Minor length, Glenohumeral rotation ranges, and load. The strength of the association between variables is population dependant. Scapula rotation in the coronal plane, and Thoracic kyphosis were not found to influence the AHD when modified in isolation.

Occupational therapists are experts in analysing the transaction between the person and the home environment and they use design and construction methods to redress any imbalance caused by the ageing process or disability. This skill is recognised by many, including governments, who utilise the expertise of occupational therapists to deliver housing modification programmes. However, the role of the occupational therapist within housing modifications services has been criticised. It is claimed that therapists' professional practice is disorganised and not founded on theoretical principles and concepts underpinning the profession. This thesis explores the development of, and a proof of concept for, a design and construction process protocol for home modifications, which seeks to address the issues highlighted above. Using a multi-method research design, the study involved three distinct phases. The first phase involved an on-line survey which was completed by 135 occupational therapists practising in the field of home modifications in the UK. Through a series of open and closed questions, the existing home modification process used by occupational therapists was explored. The second phase comprised a directed content analysis of the qualitative data generated from the online survey. Using the Occupational Therapy Intervention Process Model (Fisher, 2009) and the Design and Construction Process Protocol (Cooper et al., 2008) as the theoretical frameworks, the Home Modification Process Protocol was developed. To identify the benefits of using the Home Modification Process Protocol in occupational therapy practice, the final phase of the study used a single holistic case study design to test the concept of using the protocol in practice. The results of the first phase revealed that existing home modification processes used by occupational therapists throughout the UK lack the theoretical framework that underpins their professional practice, which is evident in other areas of clinical practice. The second part of the study revealed that a 4 phase, 9 sub-phase design and construction process protocol for home modifications could be developed using an inductive and deductive approach to the thematic analysis of the qualitative data, collected during the first phase of the study. The final phase revealed that as a concept, the Home Modification Process Protocol improved participants' understanding of their intervention as a design and construction process and importantly, it provided a theoretical framework for them to understand and articulate their practice as occupational therapists. Overall, the study found that the Home Modification Process Protocol potentially provides occupational therapists working in this area / field with a design and construction process to guide their professional practice. As the Protocol is underpinned by a combined occupational therapy and design and construction theoretical framework, it also has the potential to offer other professionals involved in modifying home environments a more systematic and effective approach to designing and delivering services for older and disabled people in their own homes.

Falling increases with age. Increasing falls incidence and associated injuries sustained by the growing older adult population contributes towards an increasing strain placed on local health services. Long-term exercise interventions have elicited signi cant reductions in falls incidence in community-dwelling older adults, and may be used in a preventative manner to reduce fall incidence in older adult populations. However, the e ectiveness of shorter interventions is less well-known. Study One of this thesis identi ed that an 18-week postural stability instruction (PSI) programme is e ective in reducing fall prevalence in frail older adults by 33%, and may improve health-related quality of life, con dence, and clinic-based strength and balance measures. However, gait performance and whole body lean mass remain unchanged. Study Two established that proprioceptive neuromuscular facilitation (PNF) stretching does not cause acute de cits in strength or muscle activation in the plantar exors and is safe for use by healthy older adults as a exibility training component of PSI interventions. Study Three found chronic strength and exibility gains following completion of a 4-week PNF stretching intervention at the ankle in old and young adults, without any acute strength de cits. Chronic strength gains during higher velocity contractions were demonstrated in dorsi exion in the older group, while exibility gains demonstrated during knee exion suggests a training e ect on the soleus muscle. These ndings indicate that and 18-week PSI programme reduces falls risk and prevalence, and that PNF training at the ankle may be used safely and e ectively by healthy older adults to improve strength and exibility. Re nement of individual PSI components to ensure implementation of the most e ective and age-appropriate strength, balance and exibility training methods is warranted. Speci cally there is a need for research to examine changes in falls incidence and risk factors following completion of an 18-week PSI intervention that incorporates PNF stretching.

Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) are devices used to deliver therapeutic agents to the lungs. Typically, inhaled active pharmaceutical ingredients (APIs) are electrically resistive materials and are prone to accumulating electrostatic charge. The build-up of charge on inhaled therapeutics has traditionally been viewed as a nuisance as it may result in problems such as weighing errors, agglomeration, adhesion to surfaces and poor flow. Energetic processing steps such as micronisation, blending, blister/capsule filling as well as fluidisation of the dose will result in a large number of particulate collisions which can result in charge transfer. Charge present on aerosol particles may also affect the in vivo performance by altering the inhaler delivery efficiency and promoting electrostatic precipitation within the lung. This study aimed to develop and assess repeatable and reliable methods of performing electrostatic measurements of particles for inhalation and to understand the relationship of charge with environmental relative humidity. A powder ladle was constructed to perform net charge measurements of inhalation grades of lactose and used to assess the extent of triboelectrification during low shear turbula blending. Results demonstrated the importance of the method of addition used to transfer a sample to a net charge measurement device. The electrical properties of DPI formulations were investigated using a Charge Decay Time Analyser. It was determined that both API concentration and relative humidity play an essential role in governing the extent to which a DPI formulation can become electrostatically charged and the subsequent rate of charge decay. Finally, the bipolar Next Generation Impactor (bp-NGI) was developed and assessed as a tool to measure the bipolar charge to mass ratios of therapeutic aerosol particles in order to address the unmet need of combining a bipolar charge measurement system with an industry standard aerosol particle size classifier.

The dosimetry of small (= < 40mm width) x-ray beams, such as those used in stereotactic radiotherapy, is much more complex than that of those used in routine clinical treatments. A thorough understanding of the properties of both small beams and small detectors is necessary to determine the optimum detector to use in each measurement situation. Accurate and reproducible experimental methods must also be developed to measure absolute and relative doses, obtain precise beam data and subsequently verify the delivered treatment dose. This work is an investigation of the above aspects of small beam dosimetry, with particular reference to the types of small fields used for stereotactic radiotherapy in the Edinburgh Cancer Centre. These are fields formed by circular stereotactic collimators (12.5 to 40mm diameter), used in conjunction with arc therapy for the treatment of small brain lesions. Several detectors were compared in the measurement of percentage depth doses, tissue maximum ratios, off axis ratios, head scatter and relative output factors, on a 6MV linac. This included the testing of three new, commercially available detectors. Clinical beam data were obtained via detector comparison and recommendations made as to the best methodology for each measurement parameter. The most accurate and reproducible technique for head scatter factors was extended to smaller stereotactic collimators (5 to 10mm diameter) and square fields with widths 10 to 20mm. These were shaped with both the movable linac collimators and the multileaf collimator and the results will be applied to the measurement of the small sub-fields used in intensity modulated radiotherapy (IMRT). A verification phantom was designed to be compatible with the stereotactic head frame and the properties of various small detectors were investigated for use in the phantom to measure point doses in both single arcs and multiple non-coplanar plans. The recommendations on beam data acquisition and dose verification were applied to two additional linacs. On all machines, the dose to the isocentre was verified in several typical treatment plans to within 2% of the calculated dose, for all clinical collimators. The results confirm the accuracy of the measurement processes used. The verification technique also provides the basis for a proposed audit of dosimetry in all stereotactic centres in the UK.

No description available.

Occupational therapy is broadly about the experience of ‘doing’ as the basis of human participation. This requires access to the means of participation: space, facilities and resources for different forms of human action. People who have experienced disability are frequently prevented from engaging in activities which other people can access, and can benefit from. Their rights to social participation at all levels are restricted, and this is a political aspect of their impairment - something that is recognized in feminist discourse in the recognition of the relationship between the personal and the political. Consequently rehabilitation has a dimension which is not just about restoring or adapting function, but also about addressing the social and political circumstances which produce barriers to occupation. The submitted works discuss a rights based approach to human occupation, which in turn derives from a narrative understanding of ‘doing’ as an individual and collective expression of actions. My most significant and original contributions to occupational therapy and occupational science concern the development of an argument for the understanding of a political dimension to human occupation. These works are accompanied by research papers which evidence some aspects of my theories. In its concentration on clinical and medically led objectives the profession has infrequently recognized the relationship between health conditions and the wider issues of social and economic disparities. Part of my work has called attention to the systematic nature of exclusions which prevent access to meaningful and purposeful occupation, and calls for therapists to work with their clients not only in terms of traditional intervention, but to address them through political alliance.