Use of fundus imaging in quantification of age-related macular change

This review will discuss the use of manual grading scales, digital photography, and automated image analysis in the quantification of fundus changes caused by age-related macular disease. Digital imaging permits processing of images for enhancement, comparison, and feature quantification, and these techniques have been investigated for automated drusen analysis. The accuracy of automated analysis systems has been enhanced by the incorporation of interactive elements, such that the user is able to adjust the sensitivity of the system, or manually add and remove pixels. These methods capitalize on both computer and human image feature recognition and the advantage of computer-based methodologies for quantification. The histogram-based adaptive local thresholding system is able to extract useful information from the image without being affected by the presence of other structures. More recent developments involve compensation for fundus background reflectance, which has most recently been combined with the Otsu method of global thresholding. This method is reported to provide results comparable with manual stereo viewing. Developments in this area are likely to encourage wider use of automated techniques. This will make the grading of photographs easier and cheaper for clinicians and researchers. © 2007 Elsevier Inc. All rights reserved.

Indwelling catheters and medical implants with FXIIIa inhibitors:a novel approach to the treatment of catheter and medical device-related infections

Central venous catheters (CVCs) are being utilized with increasing frequency in intensive care and general medical wards. In spite of the extensive experience gained in their application, CVCs are related to the long-term risks of catheter sheath formation, infection, and thrombosis (of the catheter or vessel itself) during catheterization. Such CVC-related-complications are associated with increased morbidity, mortality, duration of hospitalization, and medical care cost [1]. The present study incorporates a novel group of Factor XIIIa (FXIIIa, plasma transglutaminase) inhibitors into a lubricious silicone elastomer in order to generate an optimized drug delivery system whereby a secondary sustained drug release profile occurs following an initial burst release for catheters and other medical devices. We propose that the incorporation of FXIIIa inhibitors into catheters, stents, and other medical implant devices would reduce the incidence of catheter sheath formation, thrombotic occlusion, and associated staphylococcal infection. This technique could be used as a local delivery system for extended release with an immediate onset of action for other poorly aqueous soluble compounds. © 2012 Elsevier B.V. All rights reserved.

Growth, uniformity, local responsiveness, and system-wide adaptation in multiunit franchising

Using the resource-based view framework, we investigate the link between multiunit franchising (MUF) and performance on four key challenges in franchise chain management: growth, uniformity, local responsiveness, and system-wide adaptation. Our findings support the assertion that system growth is positively related to MUF rate within a system, in particular in relation to geographic expansion. Interestingly, while uniformity does not seem to be related to MUF rate, we find marginal support for an inverted u-shaped relationship between system-wide adaptation and MUF rate. Furthermore, the data suggest that local responsiveness and MUF rate are related in a u-shaped function.

Reforming the Swedish employment-related social security system:activation, administrative modernization and strengthening local autonomy

The Swedish system of social security has often been regarded as comprehensive and comprehensive and inclusive. During major reforms in the 1990s and 2000s, it has maintained its essential character as a popular and well-endowed provider of social security and stability. Employment-related benefits are generous in financial terms, but come with the need for recipients to remain actively engaged in the economic or educational field. However, Sweden’s geographical and demographic diversity made it necessary to increase the role of local authorities in implementing active labour market policies. This article tracks these developments since the mid-1990s, both with regard to changing the benefits system and with regard to changing local government involvement. It argues that backed by broad political support, the Swedish system has achieved the necessary modernisation and adaptation to remain a viable alternative to more neo-liberal welfare retrenchment projects conducted in other European countries.

Dynamical local models for segmentation and prediction of financial time series

In the analysis and prediction of many real-world time series, the assumption of stationarity is not valid. A special form of non-stationarity, where the underlying generator switches between (approximately) stationary regimes, seems particularly appropriate for financial markets. We introduce a new model which combines a dynamic switching (controlled by a hidden Markov model) and a non-linear dynamical system. We show how to train this hybrid model in a maximum likelihood approach and evaluate its performance on both synthetic and financial data.

DVMS 1.5: A user manual (the data visualization and modeling system)

The data available during the drug discovery process is vast in amount and diverse in nature. To gain useful information from such data, an effective visualisation tool is required. To provide better visualisation facilities to the domain experts (screening scientist, biologist, chemist, etc.),we developed a software which is based on recently developed principled visualisation algorithms such as Generative Topographic Mapping (GTM) and Hierarchical Generative Topographic Mapping (HGTM). The software also supports conventional visualisation techniques such as Principal Component Analysis, NeuroScale, PhiVis, and Locally Linear Embedding (LLE). The software also provides global and local regression facilities . It supports regression algorithms such as Multilayer Perceptron (MLP), Radial Basis Functions network (RBF), Generalised Linear Models (GLM), Mixture of Experts (MoE), and newly developed Guided Mixture of Experts (GME). This user manual gives an overview of the purpose of the software tool, highlights some of the issues to be taken care while creating a new model, and provides information about how to install & use the tool. The user manual does not require the readers to have familiarity with the algorithms it implements. Basic computing skills are enough to operate the software.

Coloring random graphs and maximizing local diversity

We study a variation of the graph coloring problem on random graphs of finite average connectivity. Given the number of colors, we aim to maximize the number of different colors at neighboring vertices (i.e. one edge distance) of any vertex. Two efficient algorithms, belief propagation and Walksat are adapted to carry out this task. We present experimental results based on two types of random graphs for different system sizes and identify the critical value of the connectivity for the algorithms to find a perfect solution. The problem and the suggested algorithms have practical relevance since various applications, such as distributed storage, can be mapped onto this problem.

Creation of relational assets through the 'library of equipment' model:an industrial modernization approach of Japan's local technology centres

SMEs with a weak internal R&D capacity show the tendency to shy away from using external sources of technical expertise. The tendency deters providers of industrial modernization services from supporting such structurally weak SMEs. This paper examines how Japan's local technology centres - kosetsushi - remove the bottleneck and reach out to a significant proportion of SMEs with a weak R&D capacity in their localities. Kosetsushi centres sustain habitual interactions with client firms through 'low information gap' services solving immediate needs and lead the clients to a riskier and longer path toward innovation capacity building. This gives kosetsushi centres a position distinct from universities and consultancies in the regional innovation system. While long-term relationships between kosetsushi centres and their client firms can increase switching costs and produce lock-in effects, a case study of two kosetsushi centres illustrates the importance of 'low-information gap' services and relational assets created thereby to the modernization of SMEs with a weak internal R&D capacity. The paper calls for long-term commitment by the public sector if it addresses the issue through modernization services.

The missing ingredient:inter-municipal cooperation and central-local relations in the UK

The thrust of the argument presented in this chapter is that inter-municipal cooperation (IMC) in the United Kingdom reflects local government's constitutional position and its exposure to the exigencies of Westminster (elected central government) and Whitehall (centre of the professional civil service that services central government). For the most part councils are without general powers of competence and are restricted in what they can do by Parliament. This suggests that the capacity for locally driven IMC is restricted and operates principally within a framework constructed by central government's policy objectives and legislation and the political expediencies of the governing political party. In practice, however, recent examples of IMC demonstrate that the practices are more complex than this initial analysis suggests. Central government may exert top-down pressures and impose hierarchical directives, but there are important countervailing forces. Constitutional changes in Scotland and Wales have shifted the locus of central- local relations away from Westminster and Whitehall. In England, the seeding of English government regional offices in 1994 has evolved into an important structural arrangement that encourages councils to work together. Within the local government community there is now widespread acknowledgement that to achieve the ambitious targets set by central government, councils are, by necessity, bound to cooperate and work with other agencies. In recent years, the fragmentation of public service delivery has affected the scope of IMC. Elected local government in the UK is now only one piece of a complex jigsaw of agencies that provides services to the public; whether it is with non-elected bodies, such as health authorities, public protection authorities (police and fire), voluntary nonprofit organisations or for-profit bodies, councils are expected to cooperate widely with agencies in their localities. Indeed, for projects such as regeneration and community renewal, councils may act as the coordinating agency but the success of such projects is measured by collaboration and partnership working (Davies 2002). To place these developments in context, IMC is an example of how, in spite of the fragmentation of traditional forms of government, councils work with other public service agencies and other councils through the medium of interagency partnerships, collaboration between organisations and a mixed economy of service providers. Such an analysis suggests that, following changes to the system of local government, contemporary forms of IMC are less dependent on vertical arrangements (top-down direction from central government) as they are replaced by horizontal modes (expansion of networks and partnership arrangements). Evidence suggests, however that central government continues to steer local authorities through the agency of inspectorates and regulatory bodies, and through policy initiatives, such as local strategic partnerships and local area agreements (Kelly 2006), thus questioning whether, in the case of UK local government, the shift from hierarchy to network and market solutions is less differentiated and transformation less complete than some literature suggests. Vertical or horizontal pressures may promote IMC, yet similar drivers may deter collaboration between local authorities. An example of negative vertical pressure was central government's change of the systems of local taxation during the 1980s. The new taxation regime replaced a tax on property with a tax on individual residency. Although the community charge lasted only a few years, it was a highpoint of the then Conservative government policy that encouraged councils to compete with each other on the basis of the level of local taxation. In practice, however, the complexity of local government funding in the UK rendered worthless any meaningful ambition of councils competing with each other, especially as central government granting to local authorities is predicated (however imperfectly) on at least notional equalisation between those areas with lower tax yields and the more prosperous locations. Horizontal pressures comprise factors such as planning decisions. Over the last quarter century, councils have competed on the granting of permission to out-of-town retail and leisure complexes, now recognised as detrimental to neighbouring authorities because economic forces prevail and local, independent shops are unable to compete with multiple companies. These examples illustrate tensions at the core of the UK polity of whether IMC is feasible when competition between local authorities heightened by local differences reduces opportunities for collaboration. An alternative perspective on IMC is to explore whether specific purposes or functions promote or restrict it. Whether in the principle areas of local government responsibilities relating to social welfare, development and maintenance of the local infrastructure or environmental matters, there are examples of IMC. But opportunities have diminished considerably as councils lost responsibility for services provision as a result of privatisation and transfer of powers to new government agencies or to central government. Over the last twenty years councils have lost their role in the provision of further-or higher-education, public transport and water/sewage. Councils have commissioning power but only a limited presence in providing housing needs, social care and waste management. In other words, as a result of central government policy, there are, in practice, currently far fewer opportunities for councils to cooperate. Since 1997, the New Labour government has promoted IMC through vertical drivers and the development; the operation of these policy initiatives is discussed following the framework of the editors. Current examples of IMC are notable for being driven by higher tiers of government, working with subordinate authorities in principal-agent relations. Collaboration between local authorities and intra-interand cross-sectoral partnerships are initiated by central government. In other words, IMC is shaped by hierarchical drivers from higher levels of government but, in practice, is locally varied and determined less by formula than by necessity and function. © 2007 Springer.

Exercise agency? The role of elite actors in local democracy in English local government: the local democracy maker.

The way in which employed senior elites in English local government exercise their agency in the practice of local democracy and local governance is considered in this thesis. The research posits the notion that elite Officers act as Local Democracy Makers as they draw on their own traditions and ideologies in responding to the dilemmas of changing policy and politics in the public realm. The study is located in the latter part of New Labour?s term of office and applies an interpretive and reflexive approach to three studies of the exercise of well being powers. The approach is one of applied ethnography through the examination of literature reviews, interviews and observations of decisions taken in the exercise of the powers of economic, environmental and social well-being are used to examine how and why the Local Democracy Makers make sense of their world in the way that they do. The research suggests that, despite prevailing narratives, local governance arrangements depend on a system of hierarchy, employed elites and local politics. The challenges of re-configuring local democracy and attempts at "hollowing out" the state have secured an influential role for the non-elected official. How officials interpret, advise, mediate and manage the exercise of local governance and local democracy presents a challenge to assumptions that public services are governed beyond or without local government. New narratives and reflections on the role of the local government Officer and the marginalisation of the elected Councillor are presented in the research. In particular, how the senior elite occupy managerial, strategic and political roles as Local Democracy Makers, offers an insight into the agency of strategic actors in localities. Consequently, the success of changes in public policy is materially influenced by how the practitioner responds to such dilemmas. The thesis concludes by suggesting that integral to the design and success of public policy implementation is the role of the Officer, and especially those practitioners that advise governing arrangements and democratic practice.

Variations of local heat transfer coefficient in piped flow of viscous liquids

Measurements were carried out to determine local coefficients of heat transfer in short lengths of horizontal pipe, and in the region of an discontinuity in pipe diameter. Laminar, transitional and turbulent flow regimes were investigated, and mixtures of propylene glycol and water were used in the experiments to give a range of viscous fluids. Theoretical and empirical analyses were implemented to find how the fundamental mechanism of forced convection was modified by the secondary effects of free convection, temperature dependent viscosity, and viscous dissipation. From experiments with the short tube it was possible to determine simple empirical relationships describing the axial distribution of the local 1usselt number and its dependence on the Reynolds and Prandtl numbers. Small corrections were made to account for the secondary effects mentioned above. Two different entrance configurations were investigated to demonstrate how conditions upstream could influence the heat transfer coefficients measured downstream In experiments with a sudden contraction in pipe diameter the distribution of local 1u3se1t number depended on the Prandtl number of the fluid in a complicated way. Graphical data is presented describing this dependence for a range of fluids indicating how the local Nusselt number varied with the diameter-ratio. Ratios up to 3.34:1 were considered. With a sudden divergence in pipe diameter, it was possible to derive the axial distribution of the local Nusse1t number for a range of Reynolds and Prandtl numbers in a similar way to the convergence experiments. Difficulty was encountered in explaining some of the measurements obtained at low Reynolds numbers, and flow visualization techniques wore used to determine the complex flow patterns which could lead to the anomalous results mentioned. Tests were carried out with divergences up to 1:3.34 to find the way in which the local Nusselt number varied with the diameter ratio, and a few experiments were carried out with very large ratios up .to 14.4. A limited amount of theoretical analysis of the 'divergence' system was carried out to substantiate certain explanations of the heat transfer mechanisms postulated.

The design of a real-time nowcasting system for localised weather

National meteorological offices are largely concerned with synoptic-scale forecasting where weather predictions are produced for a whole country for 24 hours ahead. In practice, many local organisations (such as emergency services, construction industries, forestry, farming, and sports) require only local short-term, bespoke, weather predictions and warnings. This thesis shows that the less-demanding requirements do not require exceptional computing power and can be met by a modern, desk-top system which monitors site-specific ground conditions (such as temperature, pressure, wind speed and direction, etc) augmented with above ground information from satellite images to produce `nowcasts'. The emphasis in this thesis has been towards the design of such a real-time system for nowcasting. Local site-specific conditions are monitored using a custom-built, stand alone, Motorola 6809 based sub-system. Above ground information is received from the METEOSAT 4 geo-stationary satellite using a sub-system based on a commercially available equipment. The information is ephemeral and must be captured in real-time. The real-time nowcasting system for localised weather handles the data as a transparent task using the limited capabilities of the PC system. Ground data produces a time series of measurements at a specific location which represents the past-to-present atmospheric conditions of the particular site from which much information can be extracted. The novel approach adopted in this thesis is one of constructing stochastic models based on the AutoRegressive Integrated Moving Average (ARIMA) technique. The satellite images contain features (such as cloud formations) which evolve dynamically and may be subject to movement, growth, distortion, bifurcation, superposition, or elimination between images. The process of extracting a weather feature, following its motion and predicting its future evolution involves algorithms for normalisation, partitioning, filtering, image enhancement, and correlation of multi-dimensional signals in different domains. To limit the processing requirements, the analysis in this thesis concentrates on an `area of interest'. By this rationale, only a small fraction of the total image needs to be processed, leading to a major saving in time. The thesis also proposes an extention to an existing manual cloud classification technique for its implementation in automatically classifying a cloud feature over the `area of interest' for nowcasting using the multi-dimensional signals.

The role of the greens in the local politics of West Germany.

The study examines the contribution of the Greens to the changing nature of West Germany's local politics in the 1980s. The changes correspond broadly to the politicisation and parliamentarisation of a sphere of government traditionally perceived as being "unpolitical". Building upon theories of the New Politics, it is suggested that the varying pace of socio-economic change across the Federal Republic underlies the nonuniform development of its local party systems. The party systems of localities which have witnessed rapid social and economic change are found to be more susceptible to the emergence of a New Politics dimension than those of communities in which change has occurred less rapidly. The thesis continues by addressing aspects of the Greens' role in the development of local party systems across the Federal Republic. Despite the fact that marked differences in the Greens' approach to local political participation are registered in communities of varying socio-economic types, it is argued that the Greens are largely responsible for the introduction of a "New Local Politics" dimension into West Germany's local party systems. In a comprehensive study of the Greens' role in the Mainz party system, the conflicting styles and practices of the Greens and the established political parties in the city are depicted. The failure of the Green Party to form an alliance with the SPD in the city council is attributed to the cleavage between the Greens' New Politics and the SPD's Old Politics approaches. A detailed analysis of the parliamentary initiatives introduced by the four parties represented in the Mainz council between 1984 and 1987 also supports the contention that a New Politics dimension exists in the city's party system. This dimension is identified as representing a significant source of conflict during the period of analysis.

New technology, industrial relations and white collar trade unions : the case of the National and Local Government Officers Association

The decade since 1979 has seen the most rapid introduction of microelectronic technology in the workplace. In particular, the scope offered for the application of this new technology to the area of white collar work has meant that it is a sector where trade unions have been confronted with major challenges. However the application of this technology has also provided trade unions with opportunities for exerting influence to reshape traditional attitudes to both industrial relations and the nature of work. Recent academic research on the trade union response to the introduction of new technology at the workplace suggests that, despite the resources and apparent sophistication of modern trade unions, they have not in general been able to take advantage of the opportunities offered during this period of radical technological change,the argument being that this is due both to structural weaknesses and the inappropriateness of the system of collective bargaining where new technology issues are concerned. Despite the significance of the Public Sector in employment terms, research into the response of public sector white collar trade unions to technological change has been fairly limited. This thesis sets out the approach of the National and Local Government Officers Association (NALGO), the largest solely white collar union in the world with over three quarters of a million members employed in a wide range of public service industries. The thesis examines NALGO's response at national level and, through detailed case studies, at local level in respect of Local Government and Water Industry NALGO members. The response is then evaluated and conclusions drawn in terms of a framework based upon an assessment of the key factors relevant in judging the ability of NALGO to respond effectively to the challenges brought about by the technological revolution of the last ten years.

Interaction of peptides, peptidomimetics and other drug candidates with the DI/tripeptide transport system in intestinal epithelial cells, using the in vitro caco-2 cell culture system

An uptake system was developed using Caco-2 cell monolayers and the dipeptide, glycyl-[3H]L-proline, as a probe compound. Glycyl-[3H]L-proline uptake was via the di-/tripeptide transport system (DTS) and, exhibited concentration-, pH- and temperature-dependency. Dipeptides inhibited uptake of the probe, and the design of the system allowed competitors to be ranked against one another with respect to affinity for the transporter. The structural features required to ensure or increase interaction with the DTS were defined by studying the effect of a series of glycyl-L-proline and angiotensin-converting enzyme (ACE)-inhibitor (SQ-29852) analogues on the uptake of the probe. The SQ-29852 structure was divided into six domains (A-F) and competitors were grouped into series depending on structural variations within specific regions. Domain A was found to prefer a hydrophobic function, such as a phenyl group, and was intolerant to positive charges and H+ -acceptors and donors. SQ-29852 analogues were more tolerant of substitutions in the C domain, compared to glycyl-L-proline analogues, suggesting that interactions along the length of the SQ-29852 molecule may override the effects of substitutions in the C domain. SQ-29852 analogues showed a preference for a positive function, such as an amine group in this region, but dipeptide structures favoured an uncharged substitution. Lipophilic substituents in domain D increased affinity of SQ-29852 analogues with the DTS. A similar effect was observed for ACE-NEP inhibitor analogues. Domain E, corresponding to the carboxyl group was found to be tolerant of esterification for SQ-29852 analogues but not for dipeptides. Structural features which may increase interaction for one series of compounds, may not have the same effect for another series, indicating that the presence of multiple recognition sites on a molecule may override the deleterious effect of anyone change. Modifying current, poorly absorbed peptidomimetic structures to fit the proposed hypothetical model may improve oral bioavailability by increasing affinity for the DTS. The stereochemical preference of the transporter was explored using four series of compounds (SQ-29852, lysylproline, alanylproline and alanylalanine enantiomers). The L, L stereochemistry was the preferred conformation for all four series, agreeing with previous studies. However, D, D enantiomers were shown in some cases to be substrates for the DTS, although exhibiting a lower affinity than their L, L counterparts. All the ACE-inhibitors and β-lactam antibiotics investigated, produced a degree of inhibition of the probe, and thus show some affinity for the DTS. This contrasts with previous reports that found several ACE inhibitors to be absorbed via a passive process, thus suggesting that compounds are capable of binding to the transporter site and inhibiting the probe without being translocated into the cell. This was also shown to be the case for oligodeoxynucleotide conjugated to a lipophilic group (vitamin E), and highlights the possibility that other orally administered drug candidates may exert non-specific effects on the DTS and possibly have a nutritional impact. Molecular modelling of selected ACE-NEP inhibitors revealed that the three carbonyl functions can be oriented in a similar direction, and this conformation was found to exist in a local energy-minimised state, indicating that the carbonyls may possibly be involved in hydrogen-bond formation with the binding site of the DTS.