Three-dimensional modeling of the human eye based on magnetic resonance imaging

PURPOSE. A methodology for noninvasively characterizing the three-dimensional (3-D) shape of the complete human eye is not currently available for research into ocular diseases that have a structural substrate, such as myopia. A novel application of a magnetic resonance imaging (MRI) acquisition and analysis technique is presented that, for the first time, allows the 3-D shape of the eye to be investigated fully. METHODS. The technique involves the acquisition of a T2-weighted MRI, which is optimized to reveal the fluid-filled chambers of the eye. Automatic segmentation and meshing algorithms generate a 3-D surface model, which can be shaded with morphologic parameters such as distance from the posterior corneal pole and deviation from sphericity. Full details of the method are illustrated with data from 14 eyes of seven individuals. The spatial accuracy of the calculated models is demonstrated by comparing the MRI-derived axial lengths with values measured in the same eyes using interferometry. RESULTS. The color-coded eye models showed substantial variation in the absolute size of the 14 eyes. Variations in the sphericity of the eyes were also evident, with some appearing approximately spherical whereas others were clearly oblate and one was slightly prolate. Nasal-temporal asymmetries were noted in some subjects. CONCLUSIONS. The MRI acquisition and analysis technique allows a novel way of examining 3-D ocular shape. The ability to stratify and analyze eye shape, ocular volume, and sphericity will further extend the understanding of which specific biometric parameters predispose emmetropic children subsequently to develop myopia. Copyright © Association for Research in Vision and Ophthalmology.

The molecular biology of senile plaques and neurofibrillary tangles in Alzheimer’s disease

Since the earliest descriptions of the disease, senile plaques (SP) and neurofibrillary tangles (NFT) have been regarded as the pathological 'hallmarks' of Alzheimer's disease (AD). Whether or not SP and NFT are sufficient cause to explain the neurodegeneration of AD is controversial. The major molecular constituents of these lesions, viz., beta-amyloid (Ass) and tau, have played a defining role both in the diagnosis of the disease and in studies of pathogenesis. The molecular biology of SP and NFT, however, is complex with many chemical constituents. An individual constituent could be the residue of a pathogenic gene mutation, result from cellular degeneration, or reflect the acquisition of new proteins by diffusion and molecular binding. This review proposes that the molecular composition of SP and NFT is largely a consequence of cell degeneration and the later acquisition of proteins. Such a conclusion has implications both for the diagnosis of AD and in studies of disease pathogenesis.

An investigation into the use of knowledge representation in computer-integrated manufacturing

In a certain automobile factory, batch-painting of the body types in colours is controlled by an allocation system. This tries to balance production with orders, whilst making optimally-sized batches of colours. Sequences of cars entering painting cannot be optimised for easy selection of colour and batch size. `Over-production' is not allowed, in order to reduce buffer stocks of unsold vehicles. Paint quality is degraded by random effects. This thesis describes a toolkit which supports IKBS in an object-centred formalism. The intended domain of use for the toolkit is flexible manufacturing. A sizeable application program was developed, using the toolkit, to test the validity of the IKBS approach in solving the real manufacturing problem above, for which an existing conventional program was already being used. A detailed statistical analysis of the operating circumstances of the program was made to evaluate the likely need for the more flexible type of program for which the toolkit was intended. The IKBS program captures the many disparate and conflicting constraints in the scheduling knowledge and emulates the behaviour of the program installed in the factory. In the factory system, many possible, newly-discovered, heuristics would be awkward to represent and it would be impossible to make many new extensions. The representation scheme is capable of admitting changes to the knowledge, relying on the inherent encapsulating properties of object-centres programming to protect and isolate data. The object-centred scheme is supported by an enhancement of the `C' programming language and runs under BSD 4.2 UNIX. The structuring technique, using objects, provides a mechanism for separating control of expression of rule-based knowledge from the knowledge itself and allowing explicit `contexts', within which appropriate expression of knowledge can be done. Facilities are provided for acquisition of knowledge in a consistent manner.

A comparative study of 'joined-up' working in three regeneration programme case studies

This research concerns the development of coordination and co-governance within three different regeneration programmes within one Midlands city over the period from 1999 to 2002. The New Labour government, in office since 1997, had an agenda for ‘joining-up’ government, part of which has had considerable impact in the area of regeneration policy. Joining-up government encompasses a set of related activities which can include the coordination of policy-making and service delivery. In regeneration, it also includes a commitment to operate through co-governance. Central government and local and regional organisations have sought to put this idea into practice by using what may be referred to as network management processes. Many characteristics of new policies are designed to address the management of networks. Network management is not new in this area, it has developed at least since the early 1990s with the City Challenge and Single Regeneration Budget (SRB) programmes as a way of encouraging more inclusive and effective regeneration interventions. Network management theory suggests that better management can improve decision-making outcomes in complex networks. The theories and concepts are utilised in three case studies as a way of understanding how and why regeneration attempts demonstrate real advances in inter-organisational working at certain times whilst faltering at others. Current cases are compared to the historical case of the original SRB programme as a method of assessing change. The findings suggest that: The use of network management can be identified at all levels of governance. As previous literature has highlighted, central government is the most important actor regarding network structuring. However, it can be argued that network structuring and game management are both practised by central and local actors; Furthermore, all three of the theoretical perspectives within network management (Instrumental, Institutional and Interactive), have been identified within UK regeneration networks. All may have a role to play with no single perspective likely to succeed on its own. Therefore, all could make an important contribution to the understanding of how groups can be brought together to work jointly; The findings support Klijn’s (1997) assertion that the institutional perspective is dominant for understanding network management processes; Instrumentalism continues on all sides, as the acquisition of resources remains the major driver for partnership activity; The level of interaction appears to be low despite the intentions for interactive decision-making; Overall, network management remains partial. Little attention is paid to the issues of accountability or to the institutional structures which can prevent networks from implementing the policies designed by central government, and/or the regional tier.

A longitudinal study of Chinese managerial behaviour:an inside view of decision-making under the economic reform

This research compared decision making processes in six Chinese state-owned enterprises during the period 1985 to 1988. The research objectives were: a) To examine changes in the managerial behaviour over a period of 1985 to 1988 with a focus on decision-making; b) Through this examination, to throw light on the means by which government policies on economic reform were implemented at the enterprise level; c) To illustrate problems encountered in the decentralization programme which was a major part of China's economic reform. The research was conducted by means of intensive interviews with more than eighty managers and a survey of documents relating to specific decisions. A total of sixty cases of decision-making were selected from five decision topics: purchasing of inputs, pricing of outputs, recruitment of labour, organizational change and innovation, which occurred in 1985 (or before) and in 1988/89. Data from the interviews were used to investigate environmental conditions, relations between the enterprise and its higher authority, interactions between management and the party system, the role of information, and effectiveness of regulations and government policies on enterprise management. The analysis of the data indicates that the decision processes in the different enterprises have some similarities in regard to actor involvement, the flow of decision activities, interactions with the authorities, information usage and the effect of regulations. Comparison of the same or similar decision contents over time indicates that the achievement of decentralization varied according to the topic of decision. Managerial authority was delegated to enterprises when the authorities relaxed their control over resource allocation. When acquisition of necessary resources is dependent upon the planning system or the decision matter is sensitive, because it involves change to the institutional framework (e.g. the Party), then a high degree of centralization was retained, resulting in a marginal change in managerial behaviour. The economic reform failed to increase decision efficiency and effectiveness of decision-making. The prevailing institutional frameworks were regarded as negative to the change. The research argues that the decision process is likely to be more contingent on the decision content than the organization. Three types of decision process have been conceptualized, each of them related to a certain type of decision content. This argument gives attention to the perspectives of institution and power in a way which facilitates an elaboration of organizational analysis. The problems encountered in the reform of China's industrial enterprises are identified and discussed. General recommendations for policies of further reform are offered, based on the analysis of decision process and managerial behaviour.

Real options and multinational investments : an empirical study of risk, performance and organisational awareness

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT This thesis is a cross-disciplinary study of the empirical impact of real options theory in the fields of decision sciences and performance management. Borrowing from the economics, strategy and operations research literature, the research examines the risk and performance implications of real options in firms’ strategic investments and multinational operations. An emphasis is placed on the flexibility potential and competitive advantage of multinational corporations to explore the extent to which real options analysis can be classified as best practice in management research. Using a combination of qualitative and quantitative techniques the evidence suggests that, if real options are explored and exploited appropriately, real options management can result in superior performance for multinational companies. The qualitative findings give an overview of the practical advantages and disadvantages of real options and the statistical results reveal that firms which have developed a high awareness of their real options are, as predicted by the theory, able to reduce their downside risk and increase profits through flexibility, organisational slack and multinationality. Although real options awareness does not systematically guarantee higher returns from operations, supplementary findings indicate that firms with evidence of significant investments in the acquisition of real options knowledge tend to outperform competitors which are unaware of their real options. There are three contributions of this research. First, it extends the real options and capacity planning literature to path-dependent contingent-claims analysis to underline the benefits of average type options in capacity allocation. Second, it is thought to be the first to explicitly examine the performance effects of real options on a sample of firms which have developed partial capabilities in real options analysis suggesting that real options diffusion can be key to value creation. Third, it builds a new decision-aiding framework to facilitate the use of real options in projects appraisal and strategic planning.

Export memory: a preliminary investigation of its quality, its use, and its link to export performance

Exporting is one of the main ways in which organizations internationalize. With the more turbulent, heterogeneous, sophisticated and less familiar export environment, the organizational learning ability of the exporting organization may become its only source of sustainable competitive advantage. However, achieving a competitive level of learning is not easy. Companies must be able to find ways to improve their learning capability by enhancing the different aspects of the learning process. One of these is export memory. Building from an export information processing framework this research work particularly focuses on the quality of export memory, its determinants, its subsequent use in decision-making, and its ultimate relationship with export performance. Within export memory use, four export memory use dimensions have been discovered: instrumental, conceptual, legitimizing and manipulating. Results from the qualitative study based on the data from a mail survey with 354 responses reveal that the development of export memory quality is positively related with quality of export information acquisition, the quality of export information interpretation, export coordination, and integration of the information into the organizational system. Several company and environmental factors have also been examined in terms of their relationship with export memory use. The two factors found to be significantly related to the extent of export memory use are acquisition of export information quality and export memory quality. The results reveal that export memory quality is positively related to the extent of export memory use which in turn was found to be positively related to export performance. Furthermore, results of the study show that there is only one aspect of export memory use that significantly affects export performance – the extent of export memory use. This finding could mean that there is no particular type of export memory use favored since the choice of the type of use is situation specific. Additional results reveal that environmental turbulence and export memory overload have moderating effects on the relationship between export memory use and export performance.

Dyslexia - towards diagnosis : the implications of corical laterality for children's reading difficulties

Dyslexia as a concept is defined and reviewed in a context of psychological, neurological and educational processes. In the present investigation these processes are recognised but emphasis is placed on dyslexia as a phenomenon of a written language system. The type of script system involved in the phenomenon is that of an alphabetic code representing phonological elements of language In script form related to meaning. The nature of this system is viewed In the light of current linguistic and psycholinguistic studies. These studies based as they are on an analysis of underlying written language structures provide a framework for examining the arbitrary and rule-governed system which a young child is expected to acquire. There appear to be fundamental implications for reading, spelling and writing processes; for example an alphabetic system requires recognition of consistent script-phonetic relationships, 'mediated word identification' and in particular uni-directional sensory and motor modes of perceiving. These are critical maturational factors in the young learner. The skills needed by the child for decoding and encoding such a phonemic script are described in a psychological and neuropsychological framework. Evidence for individual differences in these skills is noted and the category of the dyslexic-type learner emerges. Incidence is related to the probabilities of individual differences in lateralisation of brain function not favouring the acquisition of our script system In some cases. Dyslexia is therefore regarded as a primary difficulty consequent upon the incompatibility between:the written language system itself and the intrinsic, developmental skills of an individual's perceptual/motor system. It is recognised that secondary stresses e.g. socio-cultural deprivation, low intellectual potential or emotional trauma can further inhibit the learning process. Symptomology of a dyslexic syndrome is described.. The symptomology is seen by the writer to constitute a clinical entity. a specific category of learning difficulty for which predictive and diagnostic procedure could be devised for classroom use. Consequently an index of relevant test items has been compiled, based upon key clinical experiences and theoretical writings. This instrument knovn as the Aston Index is presented and discussed. The early stages of validation are reported and the proposed longtitudinal studies are described. The aim is to give teachers in the classroom the power and understanding to plan more effectively the earliest stages of teaching and learning; in particular to provide the means of matching the nature of the skill to be acquired with the underlying developmental patterns of each individual learner.

Studies of the mechanism of antitumour activity of N-methylformamide

NMF induces the terminal differentiation or acquisition of more benign characteristics in certain malignant cells in vitro and has good antitumour activity against murine tumours in vivo. This study was concerned with a comparison of the mechanism of antitumour activity of NMF in vitro and in vivo against the murine TLX5 lymphoma, which is sensitive to NMF in vivo. TLX5 cells incubated continuously with NMF in vitro showed a concentration and time dependent decrease in cell growth rate, which was associated with an increase in membrane permeability, a decrease in cell size and at the higher NMF concentrations, cell death. Analysis of the cell cycle after incubation with NMF indicated an early G1 phase arrest. TLX5 cells were incubated with NMF and washed free of the drug. Analysis of clonogenicity and tumourigenicity showed that all viable cells retained their proliferative potential and malignancy. Therefore, TLX5 cells exposed to NMF in vitro are not terminally differentiated, but reside in a quiescent substate which was reversed on drug removal. The intracellular GSH levels of TLX5 cells was decreased in a concentration and time dependent fashion by NMF. GSH depletion of TLX5 cells was not however a prerequisite for growth arrest, unlike the reported data for human colon carcinoma cell lines. A single administration of NMF caused a dose dependent regression of the TLX5 lymphoma in tumour bearing mice. Cell death occurred by apoptosis and necrosis. The antitumour activity of NMF was dependent on formyl C-H bond fission, with the parent drug or metabolites reaching all parts of the tumour 4h after dosing. There was a non-dose dependent increase in the S phase population, which was due to an increase in DNA synthesis, 24h after administration of NMF. NMF administration caused a decrease in GSH levels of the TLX5 lymphoma, which did not correlate with the antitumour response. However, the GSH depleting agent, BSO, marginally increased the antitumour activity of NMF.

IN VIVO analysis of ocular morphological changes during phakic accommodation

The principal theme of this thesis is the in vivo examination of ocular morphological changes during phakic accommodation, with particular attention paid to the ciliary muscle and crystalline lens. The investigations detailed involved the application of high-resolution imaging techniques to facilitate the acquisition of new data to assist in the clarification of aspects of the accommodative system that were poorly understood. A clinical evaluation of the newly available Grand Seiko Auto Ref/ Keratometer WAM-5500 optometer was undertaken to assess its value in the field of accommodation research. The device was found to be accurate and repeatable compared to subjective refraction, and has the added advantage of allowing dynamic data collection at a frequency of around 5 Hz. All of the subsequent investigations applied the WAM-5500 for determination of refractive error and objective accommodative responses. Anterior segment optical coherence tomography (AS-OCT) based studies examined the morphology and contractile response of youthful and ageing ciliary muscle. Nasal versus temporal asymmetry was identified, with the temporal aspect being both thicker and demonstrating a greater contractile response. The ciliary muscle was longer in terms of both its anterior (r = 0.49, P <0.001) and overall length (r = 0.45, P = 0.02) characteristics, in myopes. The myopic ciliary muscle does not appear to be merely stretched during axial elongation, as no significant relationship between thickness and refractive error was identified. The main contractile responses observed were a thickening of the anterior region and a shortening of the muscle, particularly anteriorly. Similar patterns of response were observed in subjects aged up to 70 years, supporting a lensocentric theory of presbyopia development. Following the discovery of nasal/ temporal asymmetry in ciliary muscle morphology and response, an investigation was conducted to explore whether the regional variations in muscle contractility impacted on lens stability during accommodation. A bespoke programme was developed to analyse AS-OCT images and determine whether lens tilt and decentration varied between the relaxed and accommodated states. No significant accommodative difference in these parameters was identified, implying that any changes in lens stability with accommodation are very slight, as a possible consequence of vitreous support. Novel three-dimensional magnetic resonance imaging (MRI) and analysis techniques were used to investigate changes in lens morphology and ocular conformation during accommodation. An accommodative reduction in lens equatorial diameter provides further evidence to support the Helmholtzian mechanism of accommodation, whilst the observed increase in lens volume challenges the widespread assertion that this structure is incompressible due to its high water content. Wholeeye MRI indicated that the volume of the vitreous chamber remains constant during accommodation. No significant changes in ocular conformation were detected using MRI. The investigations detailed provide further insight into the mechanisms of accommodation and presbyopia, and represent a platform for future work in this field.

International technology transfer and development of capabilities in Chinese state-owned manufacturing enterprises:lessons from 20 years of case research

Technological capabilities in Chinese manufacturing have been transformed in the last three decades. However, the extent to which domestic market oriented state owned enterprises (SOEs) have developed their capabilities is not clear. Six SOEs in the automotive, steel and machine tools sectors in Beijing and Tianjin have been studied since the mid-1990s to assess the capability levels attained and the role of external sources and internal efforts in developing them. Aided by government policies, acquisition of technology and their own efforts, the case study companies appear to be broadly following the East Asian late industrialisation model. All six enterprises demonstrate competences in operating established technology, managing investment and making product and process improvements. The evidence suggests that companies without foreign joint venture (JV) collaborations have made more progress in this respect.

Developing the practice of educational psychologists through theory and research

Recent research in literacy acquisition has generated detailed programs for teaching phonological awareness. The current paper will address three issues that follow from this research. Firstly, much of the past research has been conducted under conditions that are divorced from the classroom. As a result, it is not known whether the suggested teaching strategies will lead to an increase in children’s attainments when integrated into a broad reading curriculum implemented by teachers in mainstream classrooms. Secondly, these phonological interventions have been designed either to prevent the occurrence of reading difficulties or to meet the needs of failing readers. Therefore, it is not known whether the same methods would advantage all children. Thirdly, teaching children to read takes a minimum of two to three academic years. We herefore need to develop a reading curriculum that can provide the progression and differentiation to meet a wide range of needs over several academic years. We report two studies that have addressed these issues through monitoring the impact of a reading curriculum, implemented by teachers, which integrated children’s acquisition of phonological skills with broader aspects of teaching reading over three academic years. The attainments of children at all levels of ability in the experimental group were raised relative to controls, and importantly, these gains were maintained after the intervention was withdrawn. These results demonstrate that phonological awareness training can be successfully integrated into real classroom contexts and that the same methods raised the attainments of normally developing children, as well as those at risk of reading failure.

Utilisation of analogous climate locations to produce resilient biodiversity plantings for infrastructure developments

Developers have an obligation to biodiversity when considering the impact their development may have on the environment, with some choosing to go beyond the legal requirement for planning consent. Climate change projections over the 21st century indicate a climate warming and thus the species selected for habitat creation need to be able to withstand the pressures associated with these forecasts. A process is therefore required to identify resilient plantings for sites subject to climate change. Local government ecologists were consulted on their views on the use of plants of non-native provenance or how they consider resilience to climate change as part of their planting recommendations. There are mixed attitudes towards non-native species, but with studies already showing the impact climate change is having on biodiversity, action needs to be taken to limit further biodiversity loss, particularly given the heavily fragmented landscape preventing natural migration. A methodology has been developed to provide planners and developers with recommendations for plant species that are currently adapted to the climate the UK will experience in the future. A climate matching technique, that employs a GIS, allows the identification of European locations that currently experience the predicted level of climate change at a given UK location. Once an appropriate location has been selected, the plant species present in this area are then investigated for suitability for planting in the UK. The methodology was trialled at one site, Eastern Quarry in Kent, and suitable climate matched locations included areas in north-western France. Through the acquisition of plant species data via site visits and online published material, a species list was created, which considered original habitat design, but with added resilience to climate change.

The impact of flash intensity on retinal vessel oxygen saturation measurements using dual wavelength oximetry

PURPOSE. To establish the optimal flash settings for retinal vessel oxygen saturation parameters using dual-wavelength imaging in a multiethnic group. METHODS. Twelve healthy young subjects (mean age 32 years [SD 7]; three Mediterranean, two South Asian, and seven Caucasian individuals) underwent retinal vessel oxygen saturation measurements using dual-wavelength oximetry, noncontact tonometry, and manual sphygmomanometry. In order to evaluate the impact of flash intensity, we obtained three images (fundus camera angle 30°, ONH centered) per flash setting. Flash settings of the fundus camera were increased in steps of 2 (initial setting of 6 and the final of 22), which reflect logarithmic increasing intensities from 13.5 to 214 Watt seconds (Ws). RESULTS. Flash settings below 27 Ws were too low to obtain saturation measurements, whereas flash settings of more than 214 Ws resulted in overexposed images. Retinal arteriolar and venular oxygen saturation was comparable at flash settings of 27 to 76 Ws (arterioles' range: 85%-92%; venules' range: 45%-53%). Higher flash settings lead to increased saturation measurements in both retinal arterioles (up to 110%) and venules (up to 92%), with a more pronounced increase in venules. CONCLUSIONS. Flash intensity has a significant impact on retinal vessel oxygen saturation measurements using dual-wavelength retinal oximetry. High flash intensities lead to supranormal oxygen saturation measurements with a magnified effect in retinal venules compared with arteries. In addition to even retinal illumination, the correct flash setting is of paramount importance for clinical acquisition of images in retinal oximetry. We recommend flash settings between 27 to 76 Ws. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Sucrose cryo-protection facilitates imaging of whole eye sections by MALDI mass spectrometry

Sucrose is used as a cryo-preservation agent on large mammalian eyes post formalin fixation and is shown to reduce freezing artefacts allowing the collection of 12-μm thick sections from these large aqueous samples. The suitability of this technique for use in MALDI imaging experiments is demonstrated by the acquisition of the first images of lipid distributions within whole sagittal porcine eye sections. © 2012 John Wiley & Sons, Ltd.