Progressive supranuclear palsy (PSP):A quantitative study of the pathological changes in cortical and subcortical regions of eight cases

In eight cases of progressive supranuclear palsy (PSP), neurofibrillary tangles (NFT) were numerous in the substantia nigra (SN), red nucleus (RN), locus caeruleus (LC), pontine nuclei (PN), and inferior olivary nucleus (ION) and abnormally enlarged neurons (EN) in the ION, LC and PN. Loss of Purkinje cells was evident in the cerebellum. Tufted astrocytes (TA) were abundant in the striatum, SN and RN and glial inclusions ('coiled bodies') (GI) in the midbrain (SN, RN) and pons (LC). Neuritic plaques were frequent in one case. NFT, GI, and TA densities were uncorrelated in most areas. NFT and EN densities were positively correlated in the midbrain and surviving neurons and disease duration in several areas. These results suggest: 1) predominantly subcortical pathology in PSP with widespread NFT while TA and GI have a more localized distribution, 2) little correlation between neuronal and glial pathologies, and 3) shorter duration cases may be more likely to develop cortical pathology. © 2007 Springer-Verlag.

Spatial topography of the neurofibrillary tangles in cortical and subcortical regions in progressive supranuclear palsy

Objective: To study the topography of neurofibrillary tangles (NFT) in cortical and subcortical areas in progressive supranuclear palsy (PSP). Methods: Pattern analysis was carried out on tau-positive NFT in eight PSP cases. Results: Of the areas studied, NFT were randomly distributed in 68%, regularly distributed in 3%, and clustered in 29%. A regular distribution of clusters was more frequent in cortical than subcortical areas. Conclusion: NFT topography in subcortical areas was similar to inclusions in the synucleinopathy multiple system atrophy (MSA) but in cortical areas was comparable to other tauopathies. © 2006 Elsevier Ltd. All rights reserved.

High growth firms, jobs and peripheral regions:the case of Scotland

Enterprise policy is increasingly favouring support for high growth firms (HGFs). However, this may be less effective in promoting new jobs and economic development in peripheral regions. This issue is addressed by a study of HGFs in Scotland. Scottish HGFs differ in a number of respects from the stylised facts in the literature. They create less employment than their counterparts elsewhere in the UK. Most have a significant physical presence outside of Scotland, thereby reducing their Scottish 'footprint' and domestic job creation. Scottish HGFs appear to have a high propensity to be acquired, increasing the susceptibility of the head office to closure. The evidence suggests that the tendency towards 'policy universalism' in the sphere of entrepreneurship policy is problematic.

Vortex-density fluctuations, energy spectra, and vortical regions in superfluid turbulence

Measurements of the energy spectrum and of the vortex-density fluctuation spectrum in superfluid turbulence seem to contradict each other. Using a numerical model, we show that at each instance of time the total vortex line density can be decomposed into two parts: one formed by metastable bundles of coherent vortices, and one in which the vortices are randomly oriented. We show that the former is responsible for the observed Kolmogorov energy spectrum, and the latter for the spectrum of the vortex line density fluctuations.

Corporate Social Reporting (CSR) in emerging economies: a review and future direction

Purpose – Previous reviews of Corporate Social Reporting (CSR) literature have tended to focus on developed economies. The aim of this study is to extend reviews of CSR literature to emerging economies. Design/methodology/approach – A desk-based research method, using a classification framework of three categories. Findings – Most CSR studies in emerging economies have concentrated on the Asia-Pacific and African regions and are descriptive in nature, used content analysis methods and measured the extent and volume of disclosures contained within the annual reports. Such studies provide indirect explanation of the reasons behind CSR adoption, but of late, a handful of studies have started to probe managerial motivations behind CSR directly through in-depth interviews finding that CSR agendas in emerging economies are largely driven by external forces, namely pressures from parent companies, international market and international agencies.

Hymer and uneven development revisited:Foreign Direct Investment and regional inequalities

Picking up on one of Hymer's key contributions, this paper examines the impact that inward foreign direct investment (FDI) into the UK has on the patterns of development, both within and across regions. Using a panel of data for the manufacturing sector, the paper illustrates that even where one isolates the effect on the domestic sector alone, inward investment acts to increase the demand for skilled, relative to unskilled labour, and also generates the expected agglomeration effects in terms of the demand for capital investment. The paper then goes on to draw certain policy comparisons between these findings and the desired aim of attracting FDI, notably to increase demand for labour in those regions suffering structural unemployment, and secondly to reduce the disparities between regions.

Intra-industry foreign direct investment, uneven development and globalization:the legacy of Stephen Hymer

This paper revisits the issue of intra-industry foreign direct investment (FDI). This issue was considered in Stephen Hymer's early work, but was not subsequently developed, and was largely ignored in the literature for some time. Using the example of the UK, this paper traces the patterns of intra-industry FDI, both across countries and industries, for both the manufacturing and service sectors. Despite the undoubted increase in the integration of goods and factor markets since the time of Hymer's writing, the analysis presented here shows that the pattern has changed little in the last 40 years. The paper then goes on to discuss the motives for intra-industry FDI, relating it to technology flows and factor cost differentials. Finally, we present some analysis relating intra-industry FDI to uneven development, both between developed and developing countries, and between regions of a developed country. It is clear that intra-industry FDI is still very much a developed country phenomenon, as Hymer suggested, with both developing countries and poorer regions of developed countries unlikely to reap any of the benefits. In this context, one-way and two-way FDI must be seen as different phenomena within the debate on globalisation. © The Author 2005. Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved.

The interaction of luminance and texture amplitude in surface depth perception

Previous studies have suggested separate channels for detection of first-order luminance modulations (LM) and second-order modulations of the local amplitude (AM) of a texture. Mixtures of LM and AM with different phase relationships appear very different: in-phase compounds (LM + AM) look like 3-D corrugated surfaces, while out-of-phase compounds (LM - AM) appear flat and/or transparent. This difference may arise because the in-phase compounds are consistent with multiplicative shading, while the out-of-phase compounds are not. We investigated the role of these modulation components in surface depth perception. We used a textured background with thin bars formed by local changes in luminance and/or texture amplitude. These stimuli appear as embossed surfaces with wide and narrow regions. Keeping the AM modulation depth fixed at a suprathreshold level, we determined the amount of luminance contrast required for observers to correctly indicate the width (narrow or wide) of 'raised' regions in the display. Performance (compared to the LM-only case) was facilitated by the presence of AM, but, unexpectedly, performance for LM - AM was as good as for LM + AM. Thus, these results suggest that there is an interaction between first-order and second-order mechanisms during depth perception based on shading cues, but the phase dependence is not yet understood.

The interaction of luminance and texture amplitude in depth perception

Previous studies have suggested separate channels for the detection of first-order luminance (LM) and second-order modulations of the local amplitude (AM) of a texture (Schofield and Georgeson, 1999 Vision Research 39 2697 - 2716; Georgeson and Schofield, 2002 Spatial Vision 16 59). It has also been shown that LM and AM mixtures with different phase relationships are easily separated in identification tasks, and (informally) appear very different with the in-phase compound (LM + AM), producing the most realistic depth percept. We investigated the role of these LM and AM components in depth perception. Stimuli consisted of a noise texture background with thin bars formed as local increments or decrements in luminance and/or noise amplitude. These stimuli appear as embossed surfaces with wide and narrow regions. When luminance and amplitude changes have the same sign and magnitude (LM + AM) the overall modulation is consistent with multiplicative shading, but this is not so when the two modulations have opposite sign (LM - AM). Keeping the AM modulation depth fixed at a suprathreshold level, we determined the amount of luminance contrast required for observers to correctly indicate the width (narrow or wide) of raised regions in the display. Performance (compared to the LM-only case) was facilitated by the presence of AM, but, unexpectedly, performance for LM - AM was even better than for LM + AM. Further tests suggested that this improvement in performance is not due to an increase in the detectability of luminance in the compound stimuli. Thus, contrary to previous findings, these results suggest the possibility of interaction between first-order and second-order mechanisms in depth perception.

The lateral and ventromedial prefrontal cortex work as a dynamic integrated system:evidence from FMRI connectivity analysis

Recent functional magnetic resonance imaging (fMRI) investigations of the interaction between cognition and reward processing have found that the lateral prefrontal cortex (PFC) areas are preferentially activated to both increasing cognitive demand and reward level. Conversely, ventromedial PFC (VMPFC) areas show decreased activation to the same conditions, indicating a possible reciprocal relationship between cognitive and emotional processing regions. We report an fMRI study of a rewarded working memory task, in which we further explore how the relationship between reward and cognitive processing is mediated. We not only assess the integrity of reciprocal neural connections between the lateral PFC and VMPFC brain regions in different experimental contexts but also test whether additional cortical and subcortical regions influence this relationship. Psychophysiological interaction analyses were used as a measure of functional connectivity in order to characterize the influence of both cognitive and motivational variables on connectivity between the lateral PFC and the VMPFC. Psychophysiological interactions revealed negative functional connectivity between the lateral PFC and the VMPFC in the context of high memory load, and high memory load in tandem with a highly motivating context, but not in the context of reward alone. Physiophysiological interactions further indicated that the dorsal anterior cingulate and the caudate nucleus modulate this pathway. These findings provide evidence for a dynamic interplay between lateral PFC and VMPFC regions and are consistent with an emotional gating role for the VMPFC during cognitively demanding tasks. Our findings also support neuropsychological theories of mood disorders, which have long emphasized a dysfunctional relationship between emotion/motivational and cognitive processes in depression.

Modelling and measurements on a condensing counter-flow heat exchanger

Experimental investigations and computer modelling studies have been made on the refrigerant-water counterflow condenser section of a small air to water heat pump. The main object of the investigation was a comparative study between the computer modelling predictions and the experimental observations for a range of operating conditions but other characteristics of a counterflow heat exchanger are also discussed. The counterflow condenser consisted of 15 metres of a thermally coupled pair of copper pipes, one containing the R12 working fluid and the other water flowing in the opposite direction. This condenser was mounted horizontally and folded into 0.5 metre straight sections. Thermocouples were inserted in both pipes at one metre intervals and transducers for pressure and flow measurement were also included. Data acquisition, storage and analysis was carried out by a micro-computer suitably interfaced with the transducers and thermocouples. Many sets of readings were taken under a variety of conditions, with air temperature ranging from 18 to 26 degrees Celsius, water inlet from 13.5 to 21.7 degrees, R12 inlet temperature from 61.2 to 81.7 degrees and water mass flow rate from 6.7 to 32.9 grammes per second. A Fortran computer model of the condenser (originally prepared by Carrington[1]) has been modified to match the information available from experimental work. This program uses iterative segmental integration over the desuperheating, mixed phase and subcooled regions for the R12 working fluid, the water always being in the liquid phase. Methods of estimating the inlet and exit fluid conditions from the available experimental data have been developed for application to the model. Temperature profiles and other parameters have been predicted and compared with experimental values for the condenser for a range of evaporator conditions and have shown that the model gives a satisfactory prediction of the physical behaviour of a simple counterflow heat exchanger in both single phase and two phase regions.

β-Amyloid (Aβ) deposition in elderly non-demented patients and patients with Alzheimer's disease

β-amyloid (Aβ) deposition in the medial temporal lobe (MTL) was studied in elderly non-demented (ND) cases and in patients with Alzheimer's disease (AD). In AD, Aβ deposits were present throughout the MTL although density was less in the hippocampus than the adjacent cortical regions. In the ND cases, no Aβ deposits were recorded in 6 cases and in the remaining 8 cases, Aβ deposits were confined to the cortical regions adjacent to the hippocampus. The mean density of Aβ deposits in the cortical regions examined was greater in AD than in the ND cases but there was a significant overlap between the two groups. The ratio of mature to diffuse Aβ deposits was greater in the ND than the AD cases. In both patient groups, Aβ deposits formed clusters in the cortex and many tissues exhibited a regular distribution of clusters along the cortex parallel to the pia. The mean dimension of the Aβ clusters was greater in AD than in the ND cases. Hence, few aspects of Aβ deposition appeared to consistently separate AD from ND cases. However, the spread of Aβ pathology between modular units of the cortex and into regions of the hippocampus could be factors in the development of AD. © 1994.

The interaction of fast neutrons with shielding and fusion blanket materials

In the present work the neutron emission spectra from a graphite cube, and from natural uranium, lithium fluoride, graphite, lead and steel slabs bombarded with 14.1 MeV neutrons were measured to test nuclear data and calculational methods for D - T fusion reactor neutronics. The neutron spectra measured were performed by an organic scintillator using a pulse shape discrimination technique based on a charge comparison method to reject the gamma rays counts. A computer programme was used to analyse the experimental data by the differentiation unfolding method. The 14.1 MeV neutron source was obtained from T(d,n)4He reaction by the bombardment of T - Ti target with a deuteron beam of energy 130 KeV. The total neutron yield was monitored by the associated particle method using a silicon surface barrier detector. The numerical calculations were performed using the one-dimensional discrete-ordinate neutron transport code ANISN with the ZZ-FEWG 1/ 31-1F cross section library. A computer programme based on Gaussian smoothing function was used to smooth the calculated data and to match the experimental data. There was general agreement between measured and calculated spectra for the range of materials studied. The ANISN calculations carried out with P3 - S8 calculations together with representation of the slab assemblies by a hollow sphere with no reflection at the internal boundary were adequate to model the experimental data and hence it appears that the cross section set is satisfactory and for the materials tested needs no modification in the range 14.1 MeV to 2 MeV. Also it would be possible to carry out a study on fusion reactor blankets, using cylindrical geometry and including a series of concentric cylindrical shells to represent the torus wall, possible neutron converter and breeder regions, and reflector and shielding regions.

Renal dopamine and salt-retaining states

Although generally regarded as a neurotransmitter, dopamine is also known to be secreted by the kidney whereby it promotes sodium excretion in its role as a natriuretic honnone. Peripheral dopamine may be formed by two alternative pathways; the decarboxylation of circulating L-Dopa by L-aromatic amino acid decarboxylase (LAAAD), and the desulphation of dopamine sulphate by arylsulphatase A (ASA), the latter being poorly represented in the literature. In many conditions and diseases with which sodium retention is associated, a reduced urinary excretion of dopamine has been noted implicating the involvement of dopamine in the maintenance of sodium homeostasis.This study investigates renal dopamine production via the desulphation of dopamine sulphate in a sample cohort during normal unregulated dietary sodium intake and following a low sodium regimen. After dietary salt restriction urinary dopamine sulphate levels were significantly increased, indicating that dopamine sulphate is indeed a physiological reservoir of active free dopamine, the necessity for which is reduced during self depletion. This confirmed the dopamine/dopamine sulphate pathway as one which may be relevant to the maintenance of sodium homeostasis. The activity of urinary ASA was investigated in diabetes mellitus as an example of a sodium-retaining state, and compared with that in a matched normal control group. A decreased ASA activity was anticipated, given the blunted dopamine excretion observed in many sodium-retaining states, however an unexpected increase in activity in the diabetic group was observed. Enzyme kinetic analysis of ASA showed that this was not due to the existence of an isoform having an altered affinity for dopamine sulphate. This rather paradoxical situation, that urinary-dopamine is decreased while ASA activity is increased, may be explained by the sequestering of free dopamine by autoxidation to 6-hydroxydopamine as has been hypothesised recently to occur in diabetes mellitus. To confirm the homogeneity of ASA in the normal and diabetic groups, four amplicons spanning the 3637bp intronic and exonic regions of the gene were generated by PCR. These were sequence utilising a fluorescent-dye terminator reaction using the forward PCR primer as sequencing primer. Although single nucleotide polymorphisms were observed between the two groups these occurred either in intronic regions or, when exonic, generated silent mutations, supporting the enzyme kinetic data. The expression of ASA was investigated to determine the basis of the increased activity observed in diabetes mellitus. Although a validated comparative RT-PCR assay was developed for amplification of arsa transcripts from fresh blood samples, expression analysis from archived paraffin-embedded renal tissue was complicated by the low yield and degradation of unprotected mRNA. Suggestions for the development of this work using renal cell-culture are discussed.

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.