Volitional target-selecting eye movements, such as saccades or smooth pursuit, are frequently considered distinct and separate from automatic gaze-stabilising eye movements like optokinetic nystagmus or the vestibulo-ocular reflex. This difference is regularly mapped onto brain anatomy, with distinctions made between subcortical, automatic processes; and cortical, volitional ones. However gaze-stabilising and target-selecting eye movements must work together when a moving observer views natural scenes. Yet such co-ordination would not be possible if automatic and volitional actions are sharply divided. This thesis focuses upon interactions between gaze-stabilising and target-selecting eye movements, and how these interactions can aid our understanding of the relationship between automatic and volitional processes. For a saccade executed during optokinetic nystagmus to accurately land on target, it must compensate for the ongoing optokinetic movement. It was found that targeting saccades can partially compensate for concomitant optokinetic nystagmus. The degree of compensation during optokinetic nystagmus was indistinguishable from compensation due to voluntary smooth pursuit displacements. A subsequent experiment found that locations are similarly misperceived during optokinetic nystagmus and smooth pursuit. Furthermore, saccade end-points are subject to the same perceptual mislocalisations. The next experiment established that fast-phases of optokinetic nystagmus can act like competitive saccades and cause curvature in targeting saccades. Moreover, optokinetic nystagmus fast-phases are delayed by irrelevant visual distractors in the same way as saccades (the saccadic inhibition effect). Lastly, it was established that the fast-phases of Infantile Nystagmus Syndrome also show the saccadic inhibition effect. In conclusion, target-selecting and gaze-stabilising eye movements show substantial co-ordination. Furthermore these results demonstrate considerable commonalties between ‘automatic’ and ‘volitional’ eye movements. Such commonalities provide further evidence there is no sharp distinction between automatic and volitional processes. Instead it is likely there are substantial interconnections between automatic and volitional mechanisms, and volition has a graded influence upon behaviour.

No description available.

The multifocal electroretinogram (mfERG) provides spatial and temporal information on the retina’s function in an objective manner, making it a valuable tool for monitoring a wide range of retinal abnormalities. Analysis of this clinical test can however be both difficult and subjective, particularly if recordings are contaminated with noise, for example muscle movement or blinking. This can sometimes result in inconsistencies in the interpretation process. An automated and objective method for analysing the mfERG would be beneficial, for example in multi-centre clinical trials when large volumes of data require quick and consistent interpretation. The aim of this thesis was therefore to develop a system capable of standardising mfERG analysis. A series of methods aimed at achieving this are presented. These include a technique for grading the quality of a recording, both during and after a test, and several approaches for stating if a waveform contains a physiological response or no significant retinal function. Different techniques are also utilised to report if a response is within normal latency and amplitude values. The integrity of a recording was assessed by viewing the raw, uncorrelated data in the frequency domain; clear differences between acceptable and unacceptable recordings were revealed. A scale ranging from excellent to unreportable was defined for the recording quality, first in terms of noise resulting from blinking and loss of fixation, and secondly, for muscle noise. 50 mfERG tests of varying recording quality were graded using this method with particular emphasis on the distinction between a test which should or should not be reported. Three experts also assessed the mfERG recordings independently; the grading provided by the experts was compared with that of the system. Three approaches were investigated to classify a mfERG waveform as ‘response’ or ‘no response’ (i.e. whether or not it contained a physiological response): artificial neural networks (ANN); analysis of the frequency domain profile; and the signal to noise ratio. These techniques were then combined using an ANN to provide a final classification for ‘response’ or ‘no response’. Two methods were studied to differentiate responses which were delayed from those within normal timing limits: ANN; and spline fitting. Again the output of each was combined to provide a latency classification for the mfERG waveform. Finally spline fitting was utilised to classify responses as ‘decreased in amplitude’ or ‘not decreased’. 1000 mfERG waveforms were subsequently analysed by an expert; these represented a wide variety of retinal function and quality. Classifications stated by the system were compared with those of the expert to assess its performance. An agreement of 94% was achieved between the experts and the system when making the distinction between tests which should or should not be reported. The final system classified 95% of the 1000 mfERG waveforms correctly as ‘response’ or ‘no response’. Of those said to represent an area of functioning retina it concurred with the expert for 93% of the responses when categorising them as normal or abnormal in terms of their P1 amplitude and latency. The majority of misclassifications were made when analysing waveforms with a P1 amplitude or latency close to the boundary between normal and abnormal. It was evident that the multilayered system has the potential to provide an objective and automated assessment of the mfERG test; this would not replace the expert but can provide an initial analysis for the expert to review.

The use of amniotic membrane (AM) as a dressing for ocular surface injuries has attracted the interest of the military ophthalmological community. First applied in the 1930s, the tissue is widely used today, although clinical indications for treatment are incompletely defined. While AM is most commonly stored frozen and thawed before use, dried AM is preferred for logistical reasons. Optimal preservation of the tissue is necessary to preserve its quality. The effect of drying on the physical and biological properties of the tissue are unknown. A systematic review of the evidence of AM treatment of acute chemical injuries was conducted. A framework was proposed for optimising the dried tissue through thermal, moisture sorption and surface analytical techniques. The physical properties of AM preparations were compared by mechanical testing and mathematical modelling, and an attempt was made to cross-link the AM collagen. Inflammatory aspects of the tissue were assessed by immunological techniques, zymography and macrophage assays. There is a lack of high quality evidence to support the clinical application of AM for acute burns. Complex interactions were demonstrated between the dried tissue, its excipients and moisture, suggesting novel ways of optimising the product. The mechanical properties of the dried membrane indicated that the process adversely affected the tissue, and artificial cross-linking could not be achieved. While the presence of antimicrobial peptides was not clearly established, the elution of collagenolytic enzymes was shown in therapeutic preparations of AM. The production of tumour necrosis factor by macrophages, which adhere to the spongy layer of AM, was suppressed. This project makes original contributions relevant to the use of dried AM as a biomaterial in ophthalmic surgery. Further refinements of this work, animal model experimentation and clinical trials may support its future acceptance as a clinical application.

Engineering Design Re-use refers to the utilisation of any knowledge gained from the design activity to support future design. As such, Engineering Design Re-use approaches are concerned with the support, exploration and enhancement of design knowledge prior, during and after a design activity. Modular Design is a product structuring principle whereby products are developed with distinct modules for rapid product development, efficient upgrades, and possible re-use (of the physical modules). The benefits of Modular Design centre of a greater capacity for structuring component parts to better manage the relation between market requirements and the designed product. This work explores the capabilities of Modular Design principles to provide improved support for the Engineering Design Reuse concept. The Modular Design principle is extended to structure not only the artefact's components but also their associated knowledge, to support, explore and enhance the knowledge genera ted during the evolution of the design process. A novel modular design approach, termed a Multi-Viewpoint Modular Design Methodology, is developed to address identified requirements including; support for evolutionary design knowledge, exploration and identification of inherent modularity and maintenance of the modular solution. The overall concept of the Methodology is to support the designer in evolving a modular artefact whilst utilising the principles of modularity to structure the artefact knowledge to enhance its potential applicability for re-use, the concept is termed knowledge modularity. Based on the results of a state of the art review deficiencies of existing approaches are identified including; insufficient support of evolutionary design knowledge, insufficiencies in the modelling, exploration, identification and representation of knowledge modularity, limitations in the module identification process. Declarative and procedural knowledge is developed to define a novel Modular Design Methodology to address these deficiencies. As such, the Methodology presents a formalised approach to support the modelling, optimisation and identification of modularity, both within and across viewpoints (function, working principle and structure) of the product structure, and evolutionary design knowledge. The core phenomena of a knowledge module is formalised in terms of the knowledge of design concepts and their dependencies. The formalism supports the identification of inherent modularity. An alternative model, termed the Modular Structure Matrix is developed as part of the Methodology to represent this inherent modularity. In addition, the Methodology has been developed, through a 12-month industrial residency, to address the requirements of practising designers. The Methodology is applied throughout a design activity to formalise and represent (in a matrix formalism) knowledge of the concepts embodied by a design artefact. The resulting model provides the basis to determine and represent interdependency knowledge between design concepts. The modelled concept and dependency knowledge can be utilised to support a modular analysis of the product structure both within and across design viewpoints. An optimisation and module identification mechanism can then be applied to the model and, based on the dependency data, identify inherent modularity within individual viewpoints of the product structure. Further, a mapping methodology has been developed to support the maintenance of the modular solution, and its associated artefact knowledge, across multiple viewpoints of design. The new methodology can be applied in a cyclic and iterative manner to support modularisation of the artefact design knowledge through the evolution of the design. A computational implementation has been developed to aid the evaluation of the Methodology. The functionality ofthe Methodology has been illustrated through two literature based case studies and two industrial implementation evaluations. An implementation and evaluation methodology was formalised through the rationalisation of the activities carried out during the first, and further utilised as the basis to support the second, industrial implementation. The two literature based studies evaluate the functionality of the methodologies optimisation and module identification mechanisms. These evaluations result in the identification of modular hierarchies that were not evident in the findings of the original publications. In addition, both industrial implementations result in the identification of potential improvements in the design. The evaluations illustrate the functionality of the Methodology in identifying and maintaining modularity, structuring design knowledge, supporting decision-making, learning, and improving design understanding. In addition, the evaluators outlined further potential Methodology application fields such as team design, manufacturing design and technology life-cycle management. Further the strengths and weaknesses of the Methodology, the computational implementation, and the research methodology utilised to facilitate the work presented in this thesis, are discussed. Finally, future work required to enhance the capabilities of the Multi- Viewpoint MD methodology and the functionality of the computational implementation have been identified, including; the development of more advanced modular clustering criterions, the introduction of constraints and constraint management, and the development of module costing mechanisms/metrics.

The ability to examine the appearance of the retina is of paramount importance for the diagnosis and monitoring of ophthalmic disease and for the evaluation of treatment outcomes. Direct cross-sectional imaging of retinal structure could be useful for early diagnosis and more sensitive monitoring of a variety of retinal conditions such as macular oedema and glaucoma. The view of the fundus given by ophthalmoscopy provides very limited depth information and clinicians will often have to resort to additional techniques such as flourescein angiography or visual field testing for information on structural abnormalities within the retina. Other currently available imaging techniques do not provide sufficient depth resolution to produce useful cross-sectional images of retinal structure. Optical coherence tomography (OCT) is a new imaging technique which is capable of producing cross-sectional images of the retina with a resolution that surpasses that of conventional imaging techniques. This new technique has axial resolution of around 1 O.tm and can resolve individual retinal layers, thus providing information on retinal structure. In principle, OCT is very similar to ultrasound however it makes use of a light source rather than an acoustic one. The technique is non-contact and non-invasive and is generally well tolerated by patients. This thesis describes the evaluation of this new imaging technique with regards to its potential within routine clinical practice. A number of investigations were performed to fuffil this evaluation. Tests were carried out to experimentally measure the system's resolution and the accuracy and precision of measurements made from the OCT scans. A number of factors that could affect the quality of the scans were identified and their effects were minimised wherever possible. The software provided with the system was rigorously tested and potential sources of error were identified. Various studies were undertaken to quantify the repeatability and reproducibility of measurements made from scans and normative values were established. These results were used to assess the ability of the technique to detect and quantify several retinal disorders. The potential of the technique for corneal imaging was investigated - a scanning protocol was established and customised software for processing cornea! scans was developed. The relationship between OCT bands and retinal morphology was investigated by correlating scans from canine retina with corresponding light microscopy images and by observing the position of retinal abnormalities on scans from patients with a variety of conditions that affected different parts of the retina. Finally the clinical potential of OCT was investigated by carrying out various studies on a number of retinal conditions. Further clinical studies which combine anatomical information from OCT with functional information from electrophysiology are currently underway. Current developments are aimed at improving the imaging processing features and user interface so as to provide a more robust, user-friendly system for routine clinical use.

Proliferative vitreoretinopathy, a potentially blinding condition, involves excessive proliferation of retinal pigment epithelium (RPE) cells and is the main complication following retinal detachment (RD). Complicated cases of RD are treated with silicone oil (SiO) tamponades which can potentially be used as drug reservoirs. The aim of this study was to investigate different methodologies to develop a sustained and controlled drug release of anti-proliferative and anti inflammatory drugs from SiO tamponades using all-trans retinoic acid (atRA) and ibuprofen (Ibu). In detailed studies of atRA and Ibu, including atRA degradation behaviour, the drugs were found to be non-toxic to an adult RPE cell line (ARPE 19) below 10-5 M. The solubility of both drugs in SiO was assessed using radioisotope techniques. Prodrugs of atRA and Ibu were synthesised via conjugation to polyethylene oxide (PEO), and cleavage of the resulting ester bond, toxicity towards RPE cells, solubility in SiO and release into media were assessed. Prodrug cleavage was successful in vitro for Ibu but not achieved in the case of atRA due to its highly conjugated nature. Cytotoxicity assays showed PEO attachment had no effect on cytotoxicity and PEO prodrug solubility in SiO followed the expected trend of decreasing solubility with increased PEO chain length. Overall the saturation concentration of drug in SiO achieved through the use of PEO-prodrugs was too low for an effective therapy. Lipophilic prodrugs with a poly(dimethylsiloxane) (PDMS) pro-moiety were synthesised and investigated. Their cleavage was problematic due to PDMS being highly hydrophobic and cleavage could only be achieved in vitro when a small hydrophilic spacer was added between PDMS and the drug. The effects of PDMS prodrugs as additives in SiO were investigated and the presence of PDMS-atRA in SiO was shown to have a positive effect on both atRA solubility and longevity of release. The clinically-relevant release period (6-8 weeks) was independent of atRA starting concentration but dependant on the PDMS-atRA concentration within the blend. This has potential for further development into tamponade drug reservoirs for future patient benefits. A series of linear and branched amphiphilic copolymer architectures were also evaluated as additives for SiO. Monomer selection included oligoethylene oxide methacrylate (OEGMA), 2-hydroxyethyl methacrylate, PDMS-methacrylate (PDMSMA) and the brancher PDMS-dimethacrylate (PDMSDMA). SiO solubility of p(OEGMA-co-PDMSDMA) was investigated and copolymers which contained the smallest hydrophilic and largest lipophilic components only achieved small solubility (0.1 % v/v). To overcome these solubility issues, hydrophobic PDMSMA monomer was utilised. Both linear p(PDMSMA-co-OEGMA) and branched p(PDMSMA-co-OEGMA-co-PDMSDMA) were successfully synthesised and displayed high solubility within SiO, up to 40-50 % v/v. The potential for SiO tamponades as long-acting drug reservoirs has been demonstrated after inclusion of a novel end-modified PDMS additive leading to long term release of atRA. The formation of novel polymer architectures that show considerable miscibility with SiO also shows the scope of the opportunity for further additive development to tailor release profiles.

This thesis combines theoretical, computational and experimental techniques in the study of reanalysis in human sentence comprehension. We begin by surveying the main claims of existing theories of reanalysis, and identify representation preservation as a key concept. We show that the models which most obviously feature representation preservation are those which have been formulated with in the monotonicity framework, which assumes that there are aspects of representation which are updated monotonically (i.e.non-destructively) from state to state, and that any reanalysis which requires a non-monotonic update is predicted to cause processing disruption. Next, we present a computational implementation, based on the monotonic theory of Gorrell (1995b). We argue that in constructing such a model of reanalysis, it is essential to consider not only declarative constraints, but also the computational processes through which reanalysis routines explicit, leading to novel predictions in cases where there exist more than one alternative for structural revision. I show why preferences for such reanalysis ambiguities may differ between predominantly head initial languages such as English, and head final languages such as Japanese. After this, we consider the empirical consequences of the implemented model, in particular in relation to recent experimental data concerning modifier attachment. We shoe that the model is too restrictive, and we argue that the appropriate way to expand its coverage is to apply the monotonicity constraints not directly to phrase structure, but to thematics structure. We provide a general framework which allows such non-phrase structural models to be defined, maintaining the same notion of monotonicity that was employed in the previous model. We go on to provide solutions to some computational problems which accompany this change. Finally, we present two experimental studies. The first of these considers the issue of reanalysis ambiguity, and specifically the existence of a recency preference is confirmed in off-line tasks, such as comprehension accuracy and a questionnaire experiment, but is not confirmed in self-paced reading. We discuss some possible reasons for this dissociation between the on-line and off-line results. The second experimental study considers the effect of modifier attachment in Japanese relative clause ambiguities. In this study, we confirm the influence of thematic structure on the resolution of Japanese relative clause ambiguities, and we argue that this effect should be interpreted in terms of a constraint on reanalysis.

The eye is a glucocorticoid target tissue which orchestrates expression of target genes through the glucocorticoid receptor (GR). The classical function of GR involves its interaction with glucocorticoid to influence transcription of genes involved in numerous physiological processes which include inflammation. The first line of defence in the ocular tissues includes the mucosal barrier and expression of receptors that recognise pathogen. These mechanisms activate the innate immune response during inflammation, however, in the ‘normal’ eye, immunomodulatory components exist to promote immune privilege. 11beta hydroxysteroid dehydrogenase 1 (11β-HSD1) regulates cortisol locally in tissues and has already been localised to to some ocular surface and intraocular tissues. The aim of this thesis is to evaluate the functional role of 11β-HSD1 in the eye and the orbit and whether the 11β-HSD1 can be targeted to modify various disease processes in the eye. An animal model was used to characterise the pre-receptor regulation of glucocorticoids and this was further characterised in human ocular and orbital tissues and cells. The results showed that 11β-HSD1 is functional in certain ocular (corneal epithelial, fibroblast and conjunctival fibroblast) and orbital (orbital preadipocyte) cells. The data therefore emphasises the putative role of 11β-HSDs in the ocular and orbital microenvronment.

Syftet med denna uppsats var att undersöka om det finns behov av re-designade kläder och accessoarer för yogautövare i Göteborg. Den uppsamlade informationen användes för att bedöma möjligheten till att starta ett företag vars verksamhet bygger på försäljning av yogakläder- och accessoarer genom re-design av secondhandvaror. I den teoretiska referensramen beskrivs vad marknadsföringsmix innebär, vilken inkluderar konkurrensmedel som är viktiga när man vill starta ett nytt företag, nämligen de fyra p:na. Vi har fått fram resultatet av vår marknadsundersökning genom intervjuer med sex olika yogautövare. Genom att intervjua dessa personer har vi undersökt deras köpvanor, köpbeteende, kunskaper samt inställning till re-design och secondhand samt inställning till olika prisklasser. Genom vår studie har vi kommit fram till att det finns en för liten marknad i Göteborg för försäljning av re-designade yogakläder och accessoarer. De flesta föredrar vanliga sportkläder framför yogakläder och vad gäller accessoarer så anser de flesta att de inte slits så mycket och därför köps väldigt sällan. Däremot har vi kommit fram till att man kan fundera på att i sitt företag satsa på unika re-designade yogaaccessoarer av hög kvalitet som kan fungera som en imageskapare för företaget samtidigt som man breddar ut sitt sortiment med andra relaterade varor vilka troligen köps oftare och kan generera vinst, vilket dock måste undersökas närmare. / Program: Butikschef, textil och mode