This thesis summarises a selection of forty-two studies [1-42], published by the author during the period 2000-2012, investigating the conceptual basis of Insomnia Disorder, and its evaluation and treatment, principally using cognitive and behavioural interventions. The work reflects a range of research methodologies including experimental, psychometric, qualitative and population-based studies, and randomised controlled trials. Important theoretical contributions to the literature published in this period are also included and reference is made to major textbooks, position papers, and influential chapter contribution.

It is a widely debated subject whether a patient with a diagnosis of major depression and a history of psychosis is able to use and comprehend metaphors. There are a number of studies that indicate that metaphor comprehension with this population is very reduced. However, within the context of psychotherapy metaphor is poorly defined and the concept is often applied inconsistently in academic literature. This thesis examines a commonly reported occurrence of metaphor formation in art psychotherapy and in particular, examines a type of metaphor that offers a novel perspective about interpersonal relationships called the creative relationship metaphor. This thesis aims to develop a definition of a form of metaphor that is helpful in clinical practice and understand the clinical formation of this metaphor in art psychotherapy. The first part of the thesis develops a new metaphor type, called the ‘creative relationship metaphor’ (CRM), beginning with a psycholinguistic perspective. 2 3 In summary, the key characteristics of the CRM being developed is that it is: • An interpersonal event • An image based representation which is cognitively mapped • Context dependent • A novel way of perceiving the person, thing or event The hypothesis that patients diagnosed with severe mental health issues can produce CRMs is tested through two analyses. The first analysis focuses on the defining features of the creative relationship metaphor and the second analysis focuses on the therapist’s influence on metaphor formation. In the clinical examples, the increased capacity to reflect on significant relationships is linked to the formation of the CRM. These results offer preliminary evidence suggesting that there are specific in-session interventions that support the development of the CRM in the assessment context.

Volume one represents the research component of the qualification, and is comprised of a conceptual literature review and a qualitative research paper. The conceptual review analysed a small sample of the qualitative literature on couplehood and dementia. The analysis used Dialogic/Performance Analysis (Reissman, 2008) to provide critical commentary about the implications of participant voice, linguistic features and context in research papers, and how these may uncover possible narratives that are embedded in the literature. Implications of embedded narratives have been discussed. The research portion is a piece of qualitative research that used Interpretative Phenomenological Analysis. The theoretical underpinning is that of Systemic psychology. Three couples were recruited (the husbands were all diagnosed with dementia). The couples have been presented as case studies showing themes that emerged between the partners in the couples. The discussion focuses on the perceptions of continuity/discontinuity in the relationship and shared and unshared narratives. Clinical implications and directions for future research have been proposed. Volume two represents the clinical aspects of this qualification and is comprised of five clinical case reports: A case study using dual formulation, a small scale service-related research (service evaluation), single-case experimental design, case study and the abstract from an oral presentation.

Due to concerns about international differences in treatment effectiveness, many countries are reluctant to extrapolate overseas clinical data to form the basis of guideline recommendations and intervention approval processes. The evidence on which these concerns are based, however, comes from a limited dataset, with few studies directly assessing international differences in treatment effectiveness. This study aims to assess differences in the results of cardiovascular trials between Europe, North America, and Asia using the panoramic meta-analysis approach. All meta-analyses containing randomised control trials for the treatment or prevention of cardiovascular diseases were searched for in The Cochrane Library (2000 to 2008) and Medline (2005-2008). Analysis was then conducted within and over the included meta-analyses by performing pair-wise comparisons of the trial results between Europe and North America, Europe and Asia, and North America and Asia and a universal comparison of all three continents’ trial results together. All analyses were conducted over fatal and non-fatal endpoints. The findings suggested that for both endpoints, interventions performed best in Asian trials. For fatal endpoints, a high proportion of positive trial results were observed for Japan. Further investigation showed that between-continent differences in treatment effect could be explained by between-continent differences in trial quality. However, the types of intervention prone to inter-continental differences could not be identified for fatal or non-fatal endpoints. These findings suggest that those developing guidelines and approving interventions should be cautious when extrapolating overseas data. In particular, this study highlights the importance of taking trial quality into account when extrapolating and interpreting clinical trial data from different regions.

Interpretations of osteological remains from mainland Greece during the 1960-1980s led to the suggestion that the most virulent form of malaria, Plasmodium falciparum, was prevalent between the Mesolithic and Late Bronze Age (c. 8700 cal. BC-1100 cal. BC). Although disregarded over the past decade, the theory has regained support in recent years from osteological, epidemiological, environmental and DNA studies. However, the presence of this strain of malaria in prehistoric Greece remains controversial. This thesis evaluates 1) the palaeoclimatic conditions of the Aegean between the Mesolithic and Late Bronze Age and 2) the palaeoenvironmental conditions of three archaeological settlements, with the aim of ascertaining whether the climatic and environmental conditions were as conducive for P. falciparum and the mosquito vectors as the osteological evidence suggested. Equal consideration is given to the so-called ‘lesser strains’ of malaria, P. vivax and P. malariae, the significance of which is considered to have been underestimated in previous studies.

Applicants to Medical School must be academically successful to secure a place at university. Despite their success in secondary education and the stringent entry criteria, a significant number of students fail summative assessments at the end of their First Year. This gives rises to the following question: “Why do previously high achieving students fail in the university system?” Existing models seek to distinguish between voluntary and involuntary withdrawal from university and to explain academic withdrawal in the context of an individual’s academic and social integration into a new educational environment, their commitment to the institution and their commitment to Medicine as a career. However, much of the existing literature on failure in the early years at Medical School has focused on pre-university academic ability, as demonstrated by grade achievement at the end of secondary education, and/or faculty’s perspectives of student failure. This dissertation adopts a qualitative approach to understanding success and failure in the first year at Medical School from the perspective of medical students themselves. Their perspectives are explored within the model of withdrawal and persistence proposed by Tinto (1975) and interpreted in the context of existing literature on failure in the early years of higher education in general and in Medicine in particular. These findings are further reframed within an analysis based upon Bourdieu’s Theory of Practice. This analysis considers the students’ field of operation, the relative positions of agents within the field and the capitals which allow them to hold those positions, and the habitus of the agents and the institution itself. Through this analysis, factors that students believe may predispose to success and failure are identified and discussed. This in turn leads to a consideration of how my own understanding and professional practice have developed and might develop in the future.

The present thesis is an enquiry into the nature and consistency of the idea of music as a metaphor throughout the works of the English philosopher and physician Robert Fludd (1573/4-1637). Fludd was very fond of a view of the world in which man is made of the same elements and the same proportions of the cosmos. Though this idea was slowly losing credit amongst the intellectuals of the time, Fluddean thought made some impact in the British Isles, and even more so on the continent: Johannes Kepler, for instance, wrote extensively about Fludd’s use of numerical symbolism, and stressed the differences between his own idea of harmony of the spheres and Fludd’s. After Fludd’s death, his ideas were still taken seriously amongst certain intellectual circles, e.g. in England (John Webster) and Poland (John Amos Comenius), and Fluddean thought influenced German musico-theoretical writers such as Athanasius Kircher, Andreas Werckmeister, and Johann Walther. But the subsequent centuries witnessed a general obliviousness towards Fludd. His figure began to re- emerge only in the second half of the 20th century in an increasing number of essays, papers, articles and a few books dedicated to him. What is still lacking, though, is a reassessment relying upon a more organic approach, which takes into account the entirety of Fludd’s publications and the wide range of topics covered in them. My work attempts to address this issue. The musical metaphor is one of the strongest leitmotifs in Fluddean publications, thanks to its being fit for representing man, the cosmos, and their interrelationship. Indeed the monochord, which well before Fludd was the preeminent practical and philosophical demonstration of the Pythagorean ‘divine’ proportions, rules the pages of Fludd’s earlier volumes. In later volumes, though, a new instrument takes its place: the more up-to-date weather-glass, surprisingly also linked to musical proportions. I argue that the new scientific instrument retains some of the monochord’s traits, thus representing an original re-arrangement of ‘ancient’ music; in fact, Fludd even applies it to the human pulse – an under-studied topic that I survey in detail. Following the whole Fluddean opera omnia is a task that gives one a glimpse of Fludd’s reactions to the deep changes that the intellectual and scientific world was undergoing from a perspective that has been, so far, largely neglected. This opens up to new fascinating outlooks on music, medicine and science at the beginning of the seventeenth century.

Data collected in life sciences studies mostly include a genotype description of the organism, a phenotype characterisation of the organism, and experiment-specific covariates including a description of experimental procedures and laboratory (environmental) conditions. Here, phenotype measurements are taken for Neurospora crassa (wild type) growing on agar in the standard laboratory conditions. I define a phenotype as a set of traits including apical extension velocity, branching angle, and branching distance. I use the above measures (traits) to model (estimate) biologically complex filamentous fungi network as a simplified 'In Silico Fungus' consisting of series of straight lines. Phenotype data, under the central limit theorem, is often characterized by means and standard deviations. Subsequently, P values are used to show statistical validity. Here, I question whether making normality assumption based on the popularity of such approach is always justified. Therefore, I test three different scenarios by making different assumptions about the data collected. (1) Firstly, I use the most popular approach: I assume the phenotype data comes from the continuous, normal (Gauss) distribution. Thus, I predict the future measurement outcomes by using normal (Gauss) parametric approximation. (2) Secondly, I use the most intuitive approach: I do not make any assumptions about the data collected and use it to predict the future measurement outcomes by withdrawing values pseudo randomly from the actual, raw, and discrete dataset. (3) Finally, I use the strategy balanced between the previous two: I construct a customised, continuous, and non-parametric distribution based on the data collected. Thus, I predict the future measurement outcomes by using kernel density estimation method. Subsequently, I implement all of the strategies above: (1), (2), and (3) in the in silico fungus programme to compare the computer simulation outcomes. More specifically, I compare the surface coverage, expressed as the proportion of the surface occupied by the fungus. Obtained results show that the differences between different data regimes (1), (2), and (3) are significant. Therefore, I conclude that the correct assessment of the data normality is crucial for the correct interpretation and implementation of scientific observations. I suspect the described data classification process determines successful implementation of biological findings especially in the fields such as medicine and engineering.

Infectious diseases continue to kill millions of people every year and are a significant burden on the socio-economic development of developing countries. After many years of international policy aimed at containing diseases, it has recently become an explicit aim to move towards elimination of infectious diseases. However, if this is to occur, it will be necessary to have highly eficacious diagnostic tools to ensure infected individuals are identified and treated. However, the diagnosis of infectious diseases in the developed and developing world requires the full integration of complex assays in easy-to-use platforms with robust analytical performances at low cost. Many relevant bioanalytical technologies have been developed for use in laboratories and clinics, including the current gold standard for the diagnosis of tuberculosis and malaria. The miniaturization and integration of complex functions into lab-on-a-chip (LOC)technologies using microfluidics have only had limited success in translating diagnosis assays out of a centralized laboratory to point-of-care (POC) settings, because they still remain constrained due to chip interconnection and they are either not likely to go out of research laboratories or are not appropriate for low resource settings. In this thesis, a new microfluidic platform was developed that reduced the dependency of the diagnostic procedure on large laboratory instruments providing simplicity of use, enabling the patient sample to be processed and diagnosed on a low cost, disposable biochip. Surface acoustic wave (SAW) devices, which are commonly used in mobile phone technologies, were adapted to provide controlled microfluidic functions by shaping the SAW using particular designs of electrodes and phononic structures. The control of lateral positioning of the SAW was demonstrated using a slanted finger interdigitated transducer (IDT) in a frequency tuneable manner allowing microfluidic functions such as mixing, moving and merging, sequentially performed using a single IDT both on the substrate and on a disposable chip. Alternatively, phononic bandgaps were designed to break the symmetry of the SAW in a tuneable manner and gradient index phononic crystals (GRIN-PC) lenses were designed to focus the SAW and successfully increased the amplitude of the wave by a factor 3 while the focal position could be tuned with the frequency. The potential of these techniques was demonstrated by controlling the amplitude and direction of water jet towers by the use of a phononic horn structure that allowed the enhancement of energy at defined positions and by propelling and directing a macrometer scale object in water using a slanted IDT. As proof of concepts of diagnostic devices for the developing world, an immunoassay for tuberculosis using only mobile phone technologies (SAW, light-emitting diode(LED) and complementary metaloxidesemiconductor (CMOS) camera) was demonstrated with a limit of detection of 1 pM, which is the limit required in an interferon-release assay. This limit of detection was only achievable because of the ability of SAW to increase the mixing and to reduce the non-specific binding. Furthermore, a method to enrich malaria infected cells, based on SAW and isopycnic gradient, was also demonstrated and showed an enrichment up to 100x in the equivalent of a fingerprick of blood in 3 seconds. This technique will allow to reduce the limit of detection of the current gold standard. This platform not only opens a clear road toward POC diagnostics due to its size, cost, versatility and ease in integration, but has also the potential to provide useful tools in laboratory settings for large scale, high throughput technologies.