This study presents three single case investigations of sentence processing disorders in aphasia. Assessment of the subjects was guided by models of normal sentence production and comprehension, and involved several new tests which were developed to investigate particular aspects of processing. The assessment phase generated hypotheses about where the processing system was breaking down for each patient. Although all three subjects showed disordered verb retrieval and use, different processing impairments were identified. The first subject had a deficit in the connections between verbs' semantic and phonological representations. The second subject had a hypothesised deficit in the early message level processes. The third subject had a semantic verb deficit which particularly impaired access to verbs' thematic information. Therapies were developed in the light of these hypotheses. Post therapy evaluation showed that all subjects made significant gains, although the nature and extent of their gains varied. These treatment responses are interpreted against the presumed cognitive models. The concluding discussion addresses a number of theoretical questions about the nature of the language processing system and how therapy may influence the workings of that system. Possible future directions for research are proposed.

The aims of this work were to assess the effects of different stimulus parameters on chromatic sensitivity, with particular emphasis on the effect of retinal illumination, and to investigate aspects of suprathreshold visual performance under mesopic conditions. All investigations were performed using visual psychophysical techniques. Chromatic thresholds were obtained using dynamic luminance contrast noise to isolate responses to colour signals. The effects of stimulus size and spatial distribution were examined in normal trichromats, dichromats and subjects with acquired colour vision deficiency. The chromatic sensitivity of normal trichromats was investigated with reduction in light level. Measurements were also performed to assess the possible involvement of rods in chromatic processing at threshold. Suprathreshold performance in the mesopic range was assessed in terms of the relative contributions of colour and luminance contrast to a measure of stimulus conspicuity and to visual search time. The conspicuity of a stimulus defined by colour and luminance contrast was defined as the value of achromatic contrast of a similar stimulus with an equal perceived conspicuity. An empirical model was developed from an extensive data set of conspicuity matches, to enable prediction of conspicuity for a wide range of coloured stimuli. Visual search performance for both achromatic and coloured stimuli was investigated under mesopic conditions, and results for the coloured stimuli were compared to the measure of stimulus conspiculty combined with an achromatic search time calibration. The results revealed that chromatic sensitivity is dependent on stimulus size, spatial distribution, eccentricity of presentation and level of illumination. These factors are suggested to reflect changes in cone performance and the relative cone contributions to the postreceptoral chromatic channels. Chromatic sensitivity was found to be independent of rod activity in the mesopic range, suggesting separate processing of rod signals and threshold colour signals under mesopic conditions. Measurements of stimulus conspicuity under mesopic conditions revealed individual variations in response to both luminance contrast and chromatic signals indicative of individual differences in gain control of postreceptoral mechanisms. Conspicuity was successfully modelled as a function of photopic contrast, scotopic contrast, chromatic difference to the background and the level of illumination. The nonlinear relationship between search time and luminance contrast was found to change with reduction in light level, reflecting increased contrast thresholds and diminishing effectiveness of unit physical contrast. Mesopic visual search was also found to depend on the photopic contrast, scotopic contrast and chromatic content of the stimulus, but with an apparent greater emphasis on scotopic contrast and reduced emphasis on colour compared to the measure of stimulus conspicuity. Conspicuity was successfully used to predict visual search times, and was found to be an improved indicator of search performance than either photopic or scotopic contrast.

A number of industries involved with coloured products were surveyed to assess the role of visual colour judgement in the processes and determine the industrial handicap of defective colour vision. The colour vision testing policies of the individual companies were investigated and an attempt was made to discover the industrial mistakes which could be attributed to defective colour vision. Visits were made to selected Industries to supplement information obtained from a postal survey. Discussions with Employment Medical Advisers and Industrial Medical Officers proved to be valuable. A field trial to determine the performance of paper colour matchers at standard colour vision tests was undertaken. A number of industrial jobs involving colour judgement were simulated in the laboratory. One hundred colour defective observers and a group of colour normals took part in the tasks, and an analysis of their performance is presented. In particular, comparisons are drawn between performance at these tasks and scores on standard colour vision tests. An enquiry into the colour vision tests used in school medical examinations was made and the career guidance given to colour defective children throughout England and Wales was studied. A list of occupations, jobs and careers which are likely to cause difficulty to the colour defective are presented. Finally recommendations concerning colour vision testing in industry are given.

This study aims to redesign and measure patient satisfaction and treatment of the patient flow process. Based on ontology, it will redesign the core patient flow processes with the simultaneous introduction of a patient-oriented model that will conceptualise and implement this ontological framework. A gap regarding scientific, patient-oriented, measurable frameworks has been discovered and demonstrates the need for a new healthcare management framework. As the need for this new framework is identified, this study aims at fulfilling the following objectives:  A novel redesign of core transactions of the patient flow process, based on ontology, and its supporting patient-oriented information system, from being healthcare oriented to being patient oriented.  Implement this study’s conceptualisation (patient-oriented flow) in a novel beyond any doubt, way through the function of the supporting information system as well as its measures used for the ontological process redesign.  Improve efficiency in the healthcare system through competent management of institutional resources by providing a fertile framework for strategic cooperation among patients and healthcare providers.  Assist in the development and maintenance of measurable activity-based driven results that improve patient quality value added services, turning everyday healthcare acts into healthcare facts relevant to this study’s concept. Concluding, scientific contributions of this study include the discovery and redesign of the contemporary both conceptual and structural gaps in the patient flow process and the introduction of a measurable scientific, not practical, redesign through the enterprise ontology methodology. Finally, the implementation of a novel patient-oriented framework (OS), based on universal characteristics, that results to effective GP appointment, proper diagnosis and referral, economically traceable and structurally measurable, both qualitative and quantitative, hospital inflow-outflow as well as patient awareness and patient relations management.

Tendon disorders - tendinopathies - are the primary reason form musculoskeletal consultation in primary care in the UK and the US. The molecular pathophysiology of tendinopathy remains difficult to interpret while inflammation and its role in tendinopathy have been historically ignored due to its absence in human surgical specimens. This thesis explores the role of inflammation in human tendinopathy and dissects potential molecular pathways involved in its initiation and perpetuation. Firstly I characterize inflammatory cell subtypes within a model of human tendinopathy highlighting a distinct inflammatory infiltrate particularly of mast cells and macrophages. Hypoxia and hypoxic cell death have been a long considered aetiology of tendon degeneration. In this thesis I demonstrate that hypoxia related proteins are present in early tendinopathy biopsies and thereafter in mechanistic studies demonstrate that hypoxia regulates inflammatory and apoptotic mediators in tendon cells associated with a significant shift in collagen matrix synthesis. The cytokines, interleukins 17 and 33 are emerging inflammatory mediators known to play key roles in fibroblast biology. I explored the cellular sources of IL- 17A in human tendinopathy with experiments revealing the majority of IL17A colocalised to mast cells. Moreover IL-17A induced proinflammatory cytokines and apoptosis in vitro and again resulted in a significant switch in collagen extracellular matrix production. IL 33 is a new member of the IL-1 superfamily that signals through the ST2 receptor. Herein I demonstrate that IL-33 expression is up regulated in human tendinopathic biopsies whilst rhIL-33 promotes proinflammatory cytokine release and significantly shifts matrix production toward a collagen III phenotype. WT mice undergoing a tendon injury model showed significant up regulation of IL-33 and ST2 while ST2-/- mice exhibit a reduced collagen response and biomechanical tendon strength at early time points post injury Addition of rh-IL33 increased type III collagen production and reduced the biomechanical strength of WT tendons. Furthermore mechanistic investigations has highlighted a key role for the microRNA 29 family in the modulation of collagen regulation in tendinopathy but also in controlling IL-33 induced changes as a direct target of sST2. Based on these experiments I propose IL-33 as an important and influential alarmin in early tendon injury and tendinopathy, which may be influential in the balance between reparation and degeneration in tendon disease.

In the last two decades an abundance of contact lens materials with unknown surface properties have been introduced as well as new contact lens design. Recent studies have identified the importance of physical and chemical interactions between materials and liquids. The purpose of this experimental research work was to investigate the relationship between a contact lens surface and a liquid. The wettability and hydrophilicity of both soft and rigid contact lens surfaces were determined using two novel techniques and an established method. The two novel techniques were the un-separated adherent quid/laser method and the adherent liquid/ maximum force method whereas the established technique involved monitoring the receding wetting angle and interface are a diameter of a sessile drop. Contact lens surface preparation and the method of removing a liquid from hydrated surfaces were found to be important variables when determining wettability or hydrophilicity. Experiments showed that the use of surface tension to remove liquid from hydrated surfaces significantly improved the reproducibility of subsequent measurements. Variation of the sessile drop wetting angle and interface area diameter with evaporation time demonstrated different values for different contact lenses. The clinical consequence of monitoring the receding values would be; if a material to spread tear break up time occurs the dry patches will be advanced on PMMA, rather than Paraperm contact lens. Surface hydrophilicity, if defined in terms of the maximum adherent force, describes the ability of a lens surface to attract a liquid, whereas wettability may be defined as the ability of a liquid to spread on a contact lens surface. The wettability and hydrophilicity, therefore, are two different issues. When a wetting angle is 01, or close to 0" the surface is described as wettable. Results demonstrated that Equalens had a greater surface wettability and hydrophilicity than the PMMA for pre-wear, but the post-wear hydrophilicity for PMMA was greater than Equalens. The use of each measurement method, therefore, resulted in a value that is intrinsically related to measurement method and definition. The clinical consequenceo f the valuesi s to help practitioners prescribea lens material either on wettability or hydrophilicity values. In contact lens practice, a lens surface is required to maintain a stable tear film and produce a long tear film break up time. A combination of hydrophilicty and wetting angle values can help to determine the requirement of wettability and hydrophilicity in the contact lens industry and also in practice. It can be concluded that no single test can fully describe the surface properties of contact lens surface materials, but it is proposed that information and results from a series of tests provides the most useful clinical description.

Anopheles gambiae s.l. species are reported as the most important vectors due to their ability to spread and exploit both temporary and man-made breeding sites. These factors combined with their capacity to transmit malaria, make them wide-open subject for researchers to find alternative different methods to control malaria disease. Historically, there were many attempts to limit or eradicate malaria disease by controlling the mosquitoes. The control methods varied between using insecticide-treated bed nets and indoor residual spraying, in addition to other methods that based on sterile insect technique (SIT) or genetic modification techniques. However, the success of any attempts to eliminate malaria depends on our understanding of the genetic diversity of the vectors in field. In this regard, two distinct sibling species Anopheles coluzzii and Anopheles gambiae s.s. were defined in An. gambiae complex based on single nucleotide polymorphisms intergenic spacer (IGS) near the centromere of the X chromosome. These species were found to mate assortatively even within mixed swarms. Moreover, genetic differences between them were limit to three regions that were 2L, 3L and X chromosome near the centromere regions. Several studies tried to explain the sympatric speciation process between the An. gambiae s.l. sibling species based on these islands of speciation and their role in assortative mating behaviour, but no full explanation was concluded so far. Therefore, two objectives were taken into consideration in this thesis. The first was genetic objective that aims to identify the islands of speciation that more likely responsible for assortative mating. The second was behavioural objective that aims to identify the mechanisms of assortative mating using recombinant and parental strains. These studies were important step for trying to explain the speciation process within An. gambiae s.l. species that in turn important for malaria control strategies.

No description available.

Research into acupuncture has shown that individuals continue to report favourable clinical effects despite the lack of systematic evidence supporting a point specific therapeutic effect for real acupuncture treatment. This thesis presents a qualitative study, nested within a large randomised controlled trial of acupuncture specifically designed to investigate both specific and non-specific effects of western acupuncture for osteoarthritis pain. The aim was to explore the non specific effects of acupuncture in a trial context from the participants’ perspective, in particular the therapeutic relationship and any additional influences on the patient experience that might lead to non-specific effects on outcomes. Participants were recruited from hip or knee joint replacement waiting lists and randomised to one of three treatments (real acupuncture or 2 placebo controls) and one of two consultation conditions (empathic or non- empathic). The qualitative methodology was grounded theory. Data collection combined 27 post trial audio taped, semi structured interviews with post treatment debriefing, participant and non participant observation and personal reflections. The findings of this study identified a core category of ‘forging a conviction’ and a substantive theory of ‘active trial participation’ was developed. Participants gave reasons for entering the trial and for maintaining their commitment to it, despite numerous barriers. These experiences helped to forge convictions about the trial interventions and their effects. As a result a combination of specific and non specific influences appeared to impact on the participants’ reporting of outcomes, leading to discrepancies between the quantitative and qualitative data. This theory of ‘active participation’ in clinical trials challenges some of the basic assumptions of randomized controlled trials, most notably that participants are passive recipients of an intervention and report its effects factually.

No description available.