Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

Institutional change and the challenge of policy coordination in the English regions

By contrast to major constitutional reforms elsewhere in the UK, in England's eight regions beyond London New Labour has favoured administrative decentralisation. This paper examines these institutional arrangements and assesses their capacity to develop a more integrated approach to territorial development. It confirms a growing awareness of the need to ensure greater coherence between policies to promote economic, social and environmental wellbeing. Nonetheless, a complex regional institutional architecture, inconsistent sector-based strategies, a lack of strategic leadership and blurred accountabilities hamper moves towards policy integration and the delivery of joint outcomes. Moreover, despite ongoing reforms, the absence of a clear regional agenda in a functionally designed Whitehall raises fundamental questions about the ability of sub-national bodies to work collectively to develop and implement a more coherent approach to regional policy.

Organised for inward investment? Development agencies, local government, and firms in the inward investment process

Inward investment promotion and aftercare remain central aspects of local economic development for English Regional Development Agencies, Scottish and Welsh development bodies, and local authorities in Britain. In many cases, partnership and consultation mechanisms have become integral to attracting inward investment and providing aftercare. Inward investment is thus an important area in which to explore interinstitutional relations between agents operating along diverse spatial boundaries and with different responsibilities. In this paper we analyse the local and regional institutional structures and relations characterising the inward investment process in Britain using new survey data from local authorities, regional bodies, and inward investors. We find that promotional activities have clearly defined structures which are chiefly led by the regional level. Aftercare is characterised by more collaborative arrangements involving both regional bodies and local government. However, many bodies are little used, with competition and tension between partners remaining frequent within English regions, regardless of recent institutional changes designed to reduce such problems. In Scotland and Wales, however, their national institutions are not only widely used, but they create high levels of satisfaction from firms. Hence, England has yet to respond to the effective challenges of Scotland and Wales. The analysis also highlights the limited importance of all national, regional, and local public institutions in attracting inward investors and their subsequent aftercare. The critical inputs to business decisions appear to be driven chiefly by more general supply-side conditions (for example, general skills versus local public packages) and the general attractions of a particular location.

Regional interests in Europe:Wales and Saxony as modern regions in Europe

The question of how to organize and manage sustainable regional development has recently come to the fore in many places across the industrialized countries of Central and Western Europe, and especially within the European Union (EU).This book looks at the home-grown natural, economic and social, socio-political, political and administrative conditions which policy makers face, while also being subjected to numerous external influences. Political actors in less important EU regions The question of how to organize and manage sustainable regional development has recently come to the fore in many places across the industrialized countries of Central and Western Europe, and especially within the European Union (EU).This book looks at the home-grown natural, economic and social, socio-political, political and administrative conditions which policy makers face, while also being subjected to numerous external influences. Political actors in less important EU regions attempt to create and implement strategies of regional development in the context of regional policy-making by EU institutions, national governments and the globalization process

Regional competitiveness, economic growth and stages of development

This paper positions the concept of regional competitiveness within theories concerning regional economic growth and stages of economic development. It examines the sources of regional competitiveness encompassing an analysis based on the particular stage of economic development that the nations within which regions are situated have reached. As a means to achieve this, the paper undertakes an empirical analysis of data stemming from the World Competitiveness Index of Regions, and identifies regional competitiveness as a dual concept that explains relative differences in rates of economic development across regions, as well as an understanding of the future economic growth trajectories of regions at a similar stage of economic development. As with endogenous growth and development theory, the notion of regional competitiveness presented here places knowledge, innovation and entrepreneurship at the forefront of conceptualisations of regional economic differentiation.

The global competitiveness of regions

The aim of this book is to consider theoretically the notion of the global competitiveness of regions, as well as giving attention as to how such competitiveness may be empirically measured. With this in mind, the book has three specific objectives: first, to place the concept of regional competitiveness within the context of regional economic development theory; second, to present a rationale and method for quantifying the global competitiveness of regions; and, third, to undertake the most geographically widespread analysis of regional competitiveness differences across the globe. With regard to the third goal, the analysis incorporates more than 500 regions across Europe, North and South America, Asia-Pacific, the Middle East, and the so-called BRIC economies of Brazil, Russia, India, and China. The importance of the concept of competitiveness has increased rapidly in recent years, with the issues surrounding it becoming, at the same time, more empirically refined and theoretically complex. The focus on regions reflects the growing consensus that they are the primary spatial units that compete to attract investment, and it is at the regional level that knowledge is circulated and transferred, resulting in agglomerations, or clusters, of industrial and service sector enterprises. This growing acknowledgement of the region’s role as a key spatial unit of organisation has led to attention turning to competitiveness at a more regional level. The book explores the results of the World Competitiveness Index of Regions (WCIR), covering the rankings and results of the 2014 edition. The WCIR provides a tool for analysing the development of a range of regional economies across the globe. It enables an illustration of the changing patterns of regional competitiveness on the international stage to be generated. In fundamental terms, the WCIR aims to produce an integrated and overall benchmark of the knowledge capacity, capability, and sustainability of each region, and the extent to which this knowledge is translated into economic value and transferred into the wealth of the citizens of each region.

The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor γ:evidence that retinoic acid receptor γ functions to maintain stem/progenitor cells in the absence of retinoic acid

Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)-RARα, RARβ, and RARγ-is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state.

A study of the regulatory role of retinoic acid receptor gamma in Zebrafish development

Retinoic acid (RA) is thought to signal through retinoic acid receptors (RARs), i.e. RARα, β, and γ to play important roles in embryonic development and tissue regeneration. In this thesis, the zebrafish (Danio rario) was used as a vertebrate model organism to examine the role of RARγ. Treatment of zebrafish embryos with a RARγ specific agonist reduced the axial length of developing embryos, associated with reduced somite number and loss of hoxb13a expression. There were no clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist disrupted the formation of anterior structures of the head, the cranial bones and the anterior lateral line ganglia, associated with a loss of sox9 immunopositive cells in the same regions. Pectoral fin outgrowth was blocked by treatment with the RARγ agonist; however, this was not associated with loss of tbx5a immunopositive lateral plate cells and was reversed by wash out of the RARγ agonist or co-treatment with a RARγ antagonist. Regeneration of the transected caudal fin was also blocked by RARγ agonist treatment and restored by agonist washout or antagonist co-treatment; this phenotype was associated with a localised reduction in canonical Wnt signalling. Conversely, elevated canonical Wnt signalling after RARγ treatment was seen in other tissues, including ectopically in the notochord. Furthermore, some phenotypes seen in the RARγ treated embryos were present in mutant zebrafish embryos in which canonical Wnt signalling was constitutively increased. These data suggest that RARγ plays an essential role in maintaining neural crest and mesodermal stem/progenitor cells during normal embryonic development and tissue regeneration when the receptor is in its non-ligated state. In addition, this work has provided evidence that the activation status of RARγ may regulate hoxb13a gene expression and canonical Wnt signalling. Further research is required to confirm such novel regulatory roles.