A quantitative study of the pathological changes in the cortical white matter in variant Creutzfeldt-Jakob disease (vCJD)

The objective of this study was to determine the degree of white matter pathology in the cerebral cortex in cases of variant Creutzfeldt-Jakob disease (vCJD) and to study the relationships between the white matter and grey matter pathologies. Hence, the pathological changes in cortical white matter were studied in individual gyri of the frontal, parietal, occipital, and temporal cortex in eleven cases of vCJD. Vacuolation (‘spongiform change’), deposition of the disease form of prion protein (PrPsc) in the form of discrete PrP deposits, and gliosis were observed in the white matter of virtually all cortical regions studied. Mean density of the vacuoles in the white matter was greater in the parietal lobe compared with the frontal, occipital, and temporal lobes but there were fewer glial cells in the occipital lobe compared with the other cortical regions. In the white matter of the frontal cortex, vacuole density was negatively correlated with the density of both glial cell nuclei and the PrP deposits. In addition, the densities of glial cells and PrP deposits were positively correlated in the frontal and parietal cortex. In the white matter of the frontal cortex and inferior temporal gyrus, there was a negative correlation between the densities of the vacuoles and the number of surviving neurons in laminae V/VI of the adjacent grey matter. In addition, in the frontal cortex, vacuole density in the white matter was negatively correlated with the density of the diffuse PrP deposits in laminae II/III and V/VI of the adjacent grey matter. The densities of PrP deposits in the white matter of the frontal cortex were positively correlated with the density of the diffuse PrP deposits in laminae II/III and V/V1 and with the number of surviving neurons in laminae V/V1. The data suggest that in the white matter in vCJD, gliosis is associated with the development of PrP deposits while the appearance of the vacuolation is a later development. In addition, neuronal loss and PrP deposition in the lower cortical laminae of the grey matter may be a consequence of axonal degeneration within the white matter.

A study of liquid-liquid extraction in a sieve plate column

The literature relating to sieve plate liquid extraction columns and relevant hydrodynamic phenomena have been surveyed. Mass transfer characteristics during drop formation, rise and coalescence, and related models were also reviewed. Important design parameters i.e. flooding, dispersed phase hold-up, drop size distribution, mean drop size, coalescence/flocculation zone height beneath a plate and jetting phenomena were investigated under non-mass transfer and mass transfer conditions in a 0.45m diameter, 2.3m high sieve plate column. This column had provision for four different plate designs, and variable plate spacing and downcomer heights, and the system used was Clairsol `350' (dispersed) - acetone - deionised water (continuous) with either direction of mass transfer. Drop size distributions were best described by the functions proposed by Gal-or, and then Mugele-Evans. Using data from this study and the literature, correlations were developed for dispersed phase hold-up, mean drop size in the preferred jetting regime and in the non-jetting regime, and coalescence zone height. A method to calculate the theoretical overall mass transfer coefficient allowing for the range of drop sizes encountered in the column gave the best fit to experimental data. This applied the drop size distribution diagram to estimate the volume percentage of stagnant, circulating and oscillating drops in the drop population. The overall coefficient Kcal was then calculated as the fractional sum of the predicted individual single drop coefficients and their proportion in the drop population. In a comparison between the experimental and calculated overall mass transfer coefficients for cases in which all the drops were in the oscillating regime (i.e. 6.35mm hole size plate), and for transfer from the dispersed(d) to continuous(c) phase, the film coefficient kd predicted from the Rose-Kintner correlation together with kc from that of Garner-Tayeban gave the best representation. Droplets from the 3.175mm hole size plate, were of a size to be mainly circulating and oscillating; a combination of kd from the Kronig-Brink (circulating) and Rose-Kintner (oscillating) correlations with the respective kc gave the best agreement. The optimum operating conditions for the SPC were identified and a procedure proposed for design from basic single drop data.

A quantitative study of the pathological changes in the cortical white matter in variant Creutzfeldt-Jakob disease (vCJD).

Objective: To quantify cortical white matter pathology in variant Creutzfeldt-Jakob disease (vCJD) and to correlate white and grey matter pathologies. Methods: Pathological changes were studied in immunolabeled sections of the frontal, parietal, occipital, and temporal cortex of eleven cases of vCJD. Results: Vacuolation ("spongiform change"), deposition of the disease form of prion protein (PrPsc), and a glial cell reaction were observed in the white matter. The density of the vacuoles was greatest in the white matter of the occipital cortex and glial cell density in the inferior temporal gyrus (ITG). Florid-type PrPsc deposits were present in approximately 50% of white matter regions studied. In the white matter of the frontal cortex (FC), vacuole density was negatively correlated with the densities of both glial cell nuclei and PrPsc deposits. In addition, in the frontal and parietal cortices the densities of glial cells and PrPsc deposits were positively correlated. In the FC and ITG, there was a negative correlation between the densities of the vacuoles in the white matter and the number of surviving neurons in laminae V/VI of the adjacent grey matter. In the FC, vacuole density in the white matter was negatively correlated with the density of the diffuse PrPsc deposits in laminae II/III and V/VI of the adjacent grey matter. In addition, the densities of PrPsc deposits in the white matter of the FC were positively correlated with the density of the diffuse PrPsc deposits in laminae II/III and V/VI and with the number of surviving neurons in laminae V/VI. Conclusion: The data suggest significant degeneration of cortical white matter in vCJD; the vacuolation being related to neuronal loss in the lower cortical laminae of adjacent grey matter, PrPsc deposits the result of leakage from damaged axons, and gliosis a reaction to these changes.

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.

A morphometric study of the spatial patterns of TDP-43 immunoreactive neuronal inclusions in frontotemporal lobar degeneration (FTLD) with progranulin (GRN) mutation

Mutations of the progranulin (GRN) gene are a major cause of familial frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). We studied the spatial patterns of TDP-43 immunoreactive neuronal cytoplasmic inclusions (NCI) and neuronal intranuclear inclusions (NII) in histological sections of the frontal and temporal lobe in eight cases of FTLD-TDP with GRN mutation using morphometric methods and spatial pattern analysis. In neocortical regions, the NCI were clustered and the clusters were regularly distributed parallel to the pia mater; 58% of regions analysed exhibiting this pattern. The NII were present in regularly distributed clusters in 35% of regions but also randomly distributed in many areas. In neocortical regions, the sizes of the regular clusters of NCI and NII were 400-800 µm, approximating to the size of the modular columns of the cortico-cortical projections, in 31% and 36% of regions respectively. The NCI and NII also exhibited regularly spaced clustering in sectors CA1/2 of the hippocampus and in the dentate gyrus. The clusters of NCI and NII were not spatially correlated. The data suggest degeneration of the cortico-cortical and cortico-hippocampal pathways in FTLD-TDP with GRN mutation, the NCI and NII affecting different clusters of neurons.

A study of load support and other criteria appropriate to the selection of industrial conveyor belts

A study of conveying practice demonstrates that belt conveyors provide a versatile and. much-used method of transporting bulk materials, but a review of belting manufacturers' design procedures shows that belt design and selection rules are often based on experience with all-cotton belts no longer in common use, and are net completely relevant to modern synthetic constructions. In particular, provision of the property "load support", which was not critical with cotton belts, is shown to determine the outcome of most belt selection exercises and lead to gross over specification of other design properties in many cases. The results of an original experimental investigation into this property, carried out to determine the belt and conveyor parameters that affect it, how the major role that belt stiffness plays in its provision; the basis for a belt stiffness test relevant to service conditions is given. A proposal for a more rational method of specifying load support data results from the work, but correlation of the test results with service performance is necessary before the absolute toad support capability required from a belt for given working conditions can be quantified. A study to attain this correlation is the major proposal for future work resulting from the present investigation, but a full review of the literature on conveyor design and a study of present practice within the belting industry demonstrate other, less critical, factors that could profitably be investigated. It is suggested that the most suitable method of studying these would be a rational data collection system to provide information on various facets of belt service behaviour; a basis for such a system is proposed. In addition to the work above, proposals for simplifying the present belt selection methods are made and a strain transducer suitable for use in future experimental investigations is developed.

Nations and organizations:a comparative study of English and Indian work-related attitudes and values in matched manufacturing firms

This thesis reports a cross-national study carried out in England and India in an attempt to clarify the association of certain cultural and non-cultural characteristics with people's work-related attitudes and values, and with the structure of their work organizations. Three perspectives are considered to be relevant to the objectives of the study. The contingency perspective suggests that a 'fit' between an organization's context and its structural arrangements will be fundamentally necessary for achieving success and survival. The political economy perspective argues for the determining role of the social and economic structures within which the organization operates. The culturalist perspective looks to cultural attitudes and values of organizational members for an explanation for their organization's structure. The empirical investigation was carried out in three stages in each of the two countries involved by means of surveys of cultural attitudes, work-related attitudes and organizational structures and systems. The cultural surveys suggested that Indian and English people were different from one another with regard to fear of, and respect and obedience to, their seniors, ability to cope with ambiguity, honesty, independence, expression of emotions, fatalism, reserve, and care for others; they were similar with regard to tolerance, friendliness, attitude to change, attitude to law, self-control and self-confidence, and attitude to social differentiation. The second stage of the study, involving the employees of fourteen organizations, found that the English ones perceived themselves to have more power at work, expressed more tolerance for ambiguity, and had different expectations from their job than did the Indian equivalents. The two samples were similar with respect to commitment to their company and trust in their colleagues. The findings also suggested that employees' occupations, education and age had some influences on their work-related attitudes. The final stage of the research was a study of structures, control systems, and reward and punishment policies of the same fourteen organizations which were matched almost completely on their contextual factors across the two countries. English and Indian organizations were found to be similar in terms of centralization, specialization, chief executive's span of control, height and management control strategies. English organizations, however, were far more formalized, spent more time on consultation and their managers delegated authority lower down the hierarchy than Indian organizations. The major finding of the study was the multiple association that cultural, national and contingency factors had with the structural characteristics of the organizations and with the work-related attitudes of their members. On the basis of this finding, a multi-perspective model for understanding organizational structures and systems is proposed in which the contributions made by contingency, political economy and cultural perspectives are recognized and incorporated.

Marital counselling: follow-up study of marriage guidance clients: perceptions of the agency, the process and outcomes. Available in 2 volumes.

This study is a consumer-survey conducted with former Marriage Guidance Council clients. The objectives were to identify and examine why they chose the agency, what their expectations and experiences were of marital counselling and whether anything was achieved. The material was derived from tape recorded interviews with 51 former M.G. clients (17 men and 34 women) from 42 marriages and with 21 counsellors; data from written material and a card-sort completed by the research sample; and the case record sheets of the research population (174 cases). The results from the written data of clients showed that 49% were satisfied with counselling, 25.5% were satisfied in some ways but not in others, and 25.5% were dissatisfied. Forty-six percent rated they had benefited from counselling, either a great deal or to some degree, 4% were neutral and 50% recorded they had not benefited. However the counsellors' assessments were more optimistic. It was also ascertained that 50% of the research sample eventually separated or divorced subsequent to counselling. A cross-check revealed that the majority who rated they were satisfied with counselling were those who remained married, whilst dissatisfied clients were the ones who unwillingly separated or divorced. The study then describes, discusses and assesses the experiences of clients in the light of these findings on a number of dimensions. From this it was possible to construct a summary profile of a "successful" client describing the features which would contribute to "success". Two key themes emerged from the data. (1) the discrepancy between clients expectations and the counselling offered, which included mis­ match over the aims and methods of counselling, and problem definition; and (2) the importance of the client/counsellor relationship. The various implications for the agency are then discussed which include recommendations on policy, the training of counsellors and further research.

Social psychological aspects of rape: a study of recorded rape and images of rape victimisation

This thesis is organised into four parts. In Part 1 relevant literature is reviewed and presented in three chapters. Chapter 1 examines legal and cultural factors in identifying the. boundaries of rape. Chapter 2 discusses idiographic features· and causal characteristics of rape suspects and victims. Chapter 3 reviews the evidence relating to attitudes toward rape,. attribution of responsibility to victims and the routine management of rape cases by the police. Part II comprises an experimental investigation of observer perception of the victims of violent crime. The experiment, examined the processes by which impressions were attributed to victims of personal crime. The results suggested that discrepancies from observers' stereotypes were an important factor in their polarisation of victim ratings. The relevance of. examining . both the structure and process of' impression, formation was highlighted. Part III describes an extensive field study in which the West. Midlands police files on rape for an eight year period (1071-1978) were analysed. The study revealed a large number of interesting findings related to a wide range of relevant features of the crime. Further, the impact .of common misconceptions and "myths" of rape were investigated across the legal and judicial processing of rape cases. The evidence suggests that these "myths" lead·to differential biasing effects at different stages in the process. In the final part of this thesis,. salient issues raised by the experiment and field study .are discussed·within the framework outlined in Part 1. Potential implications for future developments and research: are presented.

A study of the role of the community pharmacist in responding to symptons

Factors affecting the current role of the community pharmacist in responding to symptoms are investigated. Communication and collaboration with general medical practitioners (GPs), and the competency of pharmacists and counter assistants to perform the role of responding to symptoms, are examined. A national survey of GPs, conducted by postal questionnaire, explores attitudes towards the role of the community pharmacist in the treatment of patients' symptoms, and towards future extension of such a role. A majority (over 90%) of respondents thought that the counter prescribing activities of the pharmacist should be maintained or increased. Doctors supported treatment of most minor illnesses by pharmacists, but there was relatively little support for the deregulation of selected Prescription Only Medicines. Three quarters of respondents were in favour of joint educational meetings for pharmacists and doctors. Most GPs (85%) expressed support for a formal referral route from pharmacists to doctors, using a "notification card". A pilot study of the use of a notification card was conducted . Two thirds of the patients who were advised to see their doctor by the pharmacist subsequently did so. In most cases , the GP rated the patients' symptoms " significant" and the card "helpful". Pharmacists' and counter assistants' competency in responding to symptoms was assessed by a programme of pharmacy visits, where previously-defined symptoms were presented. Some pharmacists' questioning skills were found to be inadequate, and their knowledge not sufficiently current. Counter assistants asked fewer and less appropriate questions than did pharmacists, and assistants ' knowledge base was shown to be inadequate. Recommendations are made in relation to the education and training of pharmacists and counter assistants in responding to symptoms .

Theoretical study of Talbot-like bands observed using a laser diode below threshold

We report on a theoretical study of an interferometric system in which half of a collimated beam from a broadband optical source is intercepted by a glass slide, the whole beam subsequently being incident on a diffraction grating and the resulting spectrum being viewed using a linear CCD array. Using Fourier theory, we derive the expression of the intensity distribution across the CCD array. This expression is then examined for non-cavity and cavity sources for different cases determined by the direction from which the slide is inserted into the beam and the source bandwidth. The theoretical model shows that the narrower the source linewidth, the higher the deviation of the Talbot bands' visibility (as it is dependent on the path imbalance) from the previously known triangular shape. When the source is a laser diode below threshold, the structure of the CCD signal spectrum is very complex. The number of components present simultaneously increases with the number of grating lines and decreases with the laser cavity length. The model also predicts the appearance of bands in situations not usually associated with Talbot bands.

The development of discourse in a discourse of development:a case study of a group constructing a new discourse.

This thesis is a qualitative case study drawing on discourse analysis and ethnographic traditions. The aim of the study is to provide a description of the discourse consciously constructed by a group of six TESOL professionals in the interests of their own development. Once a week, the group met for one hour and took turns to act as 'Speaker'. The other five individuals acted as Understanders. The extra space given to the Speaker allowed a fuller articulation of a problem or focus than would normally be possible in other professional talk. The Understanders contributed moves to support this articulation. The description covers a two-year period (1998-2000) of this constructed discourse. Data, collected during this period, are drawn from several different sources: recordings, interviews, diaries and critical incident journals. The main recordings are of the actual Group Development Meetings (GDMs). Discussion of six transcribed GDMs demonstrates which discourse choices and decisions were important. In particular, the study looks at the key role played by 'Reflection' in this process. It is argued that Reflection is the key element in supporting the Speaker. The analysis of Reflection, which is considered from four perspectives (values, purpose, form and outcomes) draws on data from the featured cases. Issues relating to the transfer to other groups of this discourse-based approach to professional development are considered.

Exporting to Eastern Europe : principles and practice, including a case study of the market for fire fighting equipment

East-West trade has grown rapidly since the sixties, stimulating a parallel expansion in the literature on the subject. An extensive review of this literature shows how: (i) most of the issues involved have at their source the distinctions between East and West in political ideology and/or economic management, and (ii) there has been a tendency to keep theoretical and practical perspectives on the subject too separate. This thesis demonstrates the importance of understanding the fundamental principles implied in the first point, and represents an attempt to bridge the gap identified in the second. A detailed study of the market for fire fighting equipment in Eastern Europe is undertaken in collaboration with a medium-sized company, Angus Fire Armour Limited. Desk research methods are combined with visits to the market to assess the potential for the company's products, and recommendations for future strategy are made. The case demonstrates the scope and limitations of various research methods for the East European market, and a model for market research relevant to all companies is developed. Tne case study highlights three areas largely neglected in the literature: (i) the problems of internal company adaptation to East European conditions; (ii) the division of responsibility between foreign trade organisations; and (iii) bribery and corruption in East-West trade. Further research into the second topic - through a survey of 36 UK exporters - and the third - through analysis of publicised corruption cases - confirms the representativeness of the Angus experience, and reflects on the complexity of the Bast European import process, which does not always function as is commonly supposed. The very complexity of the problems confronting companies reaffirms the need to appreciate the principles underlying the subject, while the detailed analysis into questions of, originally, a marketing nature, reveals wider implications for East-West trade and East-West relations.

Strategic development of transport systems: a study of the physical constraints on planning processes

Investment in transport infrastructure can be highly sensitive to uncertainty. The scale and lead time of strategic transport programmes are such that they require continuing policy support and accurate forecasting. Delay, cost escalation and abandonment of projects often result if these conditions are not present. In Part One the physical characteristics of infrastructure are identified as a major constraint on planning processes. The extent to which strategies and techniques acknowledge these constraints is examined. A simple simulation model is developed to evaluate the effects on system development of variations in the scale and lead time of investments. In Part Two, two case studies of strategic infrastructure investment are analysed. The absence of a policy consensus for airport location was an important factor in the delayed resolution of the Third London Airport issue. In London itself, the traffic and environmental effects of major highway investment ultimately resulted in the abandonment of plans to construct urban motorways. In both cases, the infrastructure implications of alternative strategies are reviewed with reference to the problems of uncertainty. In conclusion, the scale of infrastructure investment is considered the most important of the constraints on the processes of transport planning. Adequate appraisal of such constraints may best be achieved by evaluation more closely aligned to policy objectives.