Comparative performance of analytical techniques for polyhexamethylene biguanide (PHMB) in ophthalmic solutions

Purpose: The use of PHMB as a disinfectant in contact lens multipurpose solutions has been at the centre of much debate in recent times, particularly in relation to the issue of solution induced corneal staining. Clinical studies have been carried out which suggest different effects with individual contact lens materials used in combination with specific PHMB containing care regimes. There does not appear to be, however, a reliable analytical technique that would detect and quantify with any degree of accuracy the specific levels of PHMB that are taken up and released from individual solutions by the various contact lens materials. Methods: PHMB is a mixture of positively charged polymer units of varying molecular weight that has maximum absorbance wavelength of 236 nm. On the basis of these properties a range of assays including capillary electrophoresis, HPLC, a nickelnioxime colorimetric technique, mass spectrophotometry, UV spectroscopy and ion chromatography were assessed paying particular attention to each of their constraints and detection levels. Particular interest was focused on the relative advantage of contactless conductivity compared to UV and mass spectrometry detection in capillary electrophoresis (CE). This study provides an overview of the comparative performance of these techniques. Results: The UV absorbance of PHMB solutions, ranging from 0.0625 to 50 ppm was measured at 236 nm. Within this range the calibration curve appears to be linear however, absorption values below 1 ppm (0.0001%) were extremely difficult to reproduce. The concentration of PHMB in solutions is in the range of 0.0002–0.00005% and our investigations suggest that levels of PHMB below 0.0001% (levels encountered in uptake and release studies) can not be accurately estimated, in particular when analysing complex lens care solutions which can contain competitively absorbing, and thus interfering, species in the solution. The use of separative methodologies, such as CE using UV detection alone is similarly limited. Alternative techniques including contactless conductivity detection offer greater discrimination in complex solutions together with the opportunity for dual channel detection. Preliminary results achieved by TraceDec1 contactless conductivity detection, (Gain 150%, Offset 150) in conjunction with the Agilent capillary electrophoresis system using a bare fused silica capillary (extended light path, 50 mid, total length 64.5 cm, effective length 56 cm) and a cationic buffer at pH 3.2, exhibit great potential with reproducible PHMB split peaks. Conclusions: PHMB-based solutions are commonly associated with the potential to invoke corneal staining in combination with certain contact lens materials. However this terminology ‘PHMBbased solution’ is used primarily because PHMB itself has yet to be adequately implicated as the causative agent of the staining and compromised corneal cell integrity. The lack of well characterised adequately sensitive assays, coupled with the range of additional components that characterise individual care solutions pose a major barrier to the investigation of PHMB interactions in the lenswearing eye.

High level data fusion

We address the question of how to obtain effective fusion of identification information such that it is robust to the quality of this information. As well as technical issues data fusion is encumbered with a collection of (potentially confusing) practical considerations. These considerations are described during the early chapters in which a framework for data fusion is developed. Following this process of diversification it becomes clear that the original question is not well posed and requires more precise specification. We use the framework to focus on some of the technical issues relevant to the question being addressed. We show that fusion of hard decisions through use of an adaptive version of the maximum a posteriori decision rule yields acceptable performance. Better performance is possible using probability level fusion as long as the probabilities are accurate. Of particular interest is the prevalence of overconfidence and the effect it has on fused performance. The production of accurate probabilities from poor quality data forms the latter part of the thesis. Two approaches are taken. Firstly the probabilities may be moderated at source (either analytically or numerically). Secondly, the probabilities may be transformed at the fusion centre. In each case an improvement in fused performance is demonstrated. We therefore conclude that in order to obtain robust fusion care should be taken to model the probabilities accurately; either at the source or centrally.

An improved tool for automated compiler construction

Since the advent of High Level Programming languages (HLPLs) in the early 1950s researchers have sought ways to automate the construction of HLPL compilers. To this end a variety of Translator Writing Tools (TWTs) have been developed in the last three decades. However, only a very few of these tools have gained significant commercial acceptance. This thesis re-examines traditional compiler construction techniques, along with a number of previous TWTs, and proposes a new improved tool for automated compiler construction called the Aston Compiler Constructor (ACC). This new tool allows the specification of complete compilation systems using a high level compiler oriented specification notation called the Compiler Construction Language (CCL). This specification notation is based on a modern variant of Backus Naur Form (BNF) and an extended variant of Attribute Grammars (AGs). The implementation and processing of the CCL is discussed along with an extensive CCL example. The CCL is shown to have an extensive expressive power, to be convenient in use, and highly readable, and thus a superior alternative to earlier TWTs, and to traditional compiler construction techniques. The execution performance of CCL specifications is evaluated and shown to be acceptable. A number of related areas are also addressed, including tools for the rapid construction of individual compiler components, and tools for the construction of compilation systems for multiprocessor operating systems and hardware. This latter area is expected to become of particular interest in future years due to the anticipated increased use of multiprocessor architectures.

Surface properties of enterococcus faecalis in relation to infective endocarditis

The effect of growth conditions on both the appearance and the antigenic profile of cells of Enterococcus faecalis was investigated using electron micrographs of ruthenium red stained and sectioned cells and SDS-PAGE and blotting techniques respectively. Three specific antigens of molecular weights 73, 40 and 37 kdaltons were of particular interest being expressed most strongly after growth in serum. This medium was deemed to most closely mimic jn vjvo growth conditions reflecting an environment similar to that which the microorganisms would encounter during bacteraemia, preceding the colonisation of the endocardium and the development of infective endocarditis. The 40 and 37 kdalton antigens were shown by immunoqold labelling to be exposed on the surface of the cells although they did not appear to be connected with the fimbriae shown to exist on some of the E. faecalis cells examined by negative staining. The 73, 40 and 37 kdalton antigens were crudely purified using sarkosyl and ammonium sulphate precipitation, and used as the basis of a serodiagnostic test for E. faecalis endocarditis using an ELISA system. This was tested in a blind trial and the success rates were 94% for positives, 90% for negatives with endocarditis caused by other organisms and 80% for E. faecalis infections other than endocarditis. The binding of E.faecalis cells to the serum proteins fibronectin and albumin was investigated using 125I labelled proteins, followed by Scatchard analysis. This showed that· E.faecalis cells do loosely bind large amounts of both of these proteins, thus surely affecting the way in which the host's immune system perceives the cells. The E.faecalis receptor for fibronectin was partially characterised and appeared to involve protein and/or carbohydrate containing components. but did not involve LTA or the 40 and 37 kdalton species specific antigens.

Isotropic compression of mixtures of hard and soft spheres

The compaction behaviour of powders with soft and hard components is of particular interest to the paint processing industry. Unfortunately, at the present time, very little is known about the internal mechanisms within such systems and therefore suitable tests are required to help in the interpretative process. The TRUBAL, Distinct Element Method (D.E.M.) program was the method of investigation used in this study. Steel (hard) and rubber (soft) particles were used in the randomly-generated, binary assemblies because they provided a sharp contrast in physical properties. For reasons of simplicity, isotropic compression of two-dimensional assemblies was also initially considered. The assemblies were first subject to quasi-static compaction, in order to define their behaviour under equilibrium conditions. The stress-strain behaviour of the assemblies under such conditions was found to be adequately described by a second-order polynomial expansion. The structural evolution of the simulation assemblies was also similar to that observed for real powder systems. Further simulation tests were carried out to investigate the effects of particle size on the compaction behaviour of the two-dimensional, binary assemblies. Later work focused on the quasi-static compaction behaviour of three-dimensional assemblies, because they represented more realistic particle systems. The compaction behaviour of the assemblies during the simulation experiments was considered in terms of percolation theory concepts, as well as more familiar macroscopic and microstructural parameters. Percolation theory, which is based on ideas from statistical physics, has been found to be useful in the interpretation of the mechanical behaviour of simple, elastic lattices. However, from the evidence of this study, percolation theory is also able to offer a useful insight into the compaction behaviour of more realistic particle assemblies.

British racial discourse: a study of political discourse about race and race-related matters at parliamentary and borough council levels

'British Racial Discourse' is a study of political discourse about race and race-related matters. The explanatory theory is adapted from current sociological studies of ideology with a heavy emphasis on the tradition developed from Marx and Engels's Feuerbach. The empirical data is drawn from the parliamentary debates on immigration and the Race Relations Bills, Conservative and Labour Party Conference Reports, and a set of interviews with Wolverhampton Borough councillors. Although the thesis has broader significance for British political discourse about race, it is particularly concerned with the responses of members of the two main political parties, rather than with the more overt and sensational racism of certain extreme Right-wing groups. Indeed, as the study progresses, it focuses more and more narrowly on the phenomenon of 'deracialised' discourse, and the details of the predominantly class-based justificatory systems of the Conservative and Labour Parties. Of particular interest are the argument forms (used in the debates on immigration and race relations) which manage to obscure the white electorate's responsibility for prejudice and discrimination. Such discoursive forms are of major significance for understanding British race relations, and their detailed examination provides an insight into the way in which 'ideological facades' are created and maintained.

Topographic studies of scalp potentials evoked by pattern presentation

The waveform and scalp distribution of the visual evoked potentials elicited by stimuli in the foveal and parafoveal regions have been investigated in a group of normal humans using a 16-channel `brain mapping' system. The waveform and topography of the responses to pattern onset and pattern reversal stimulation were investigated, using 4 x 4o full field and 4 x 2o lateral and altitudinal half-field stimuli. The responses were composed of several successive peaks which are in some respects consistent with those demonstrated by other workers using larger field sizes. The differences in the behaviour of these components with respect to the position of the stimulus in the visual field were suggestive of origins in different areas of the visual cortex and/or different visual mechanism. Of particular interest were the major early positive components `P90' and `P95' of the responses to pattern onset and pattern reversal stimulation respectively. More detailed exploration of the behaviour of these major early positive components was carried out using `M-scaled' stimuli selected to activate one square centimetre patches of striate cortex and associated extrastriate re-projections, positioned at different points in the foveal and parafoveal area of the visual field. The inter- and intra-subject variability in amplitude and localisation of the signals elicited by these targets was considered to be a reflection of the individual variations in relationship of visual field projections with the pattern of gyri and fissures on the proximal surface of the occipital lobe. The behaviour of component P90 of the onset response is consistent with a lateral origin in extrastriate visual cortex; that of P95 of the pattern reversal response is consistent in some respects with a striate cortical origin, but in others with a partial origin in extrastriate cortex.

Incoherent fibre supercontinuum generation for all-optical random number generation

Random number generation is a central component of modern information technology, with crucial applications in ensuring communications and information security. The development of new physical mechanisms suitable to directly generate random bit sequences is thus a subject of intense current research, with particular interest in alloptical techniques suitable for the generation of data sequences with high bit rate. One such promising technique that has received much recent attention is the chaotic semiconductor laser systems producing high quality random output as a result of the intrinsic nonlinear dynamics of its architecture [1]. Here we propose a novel complementary concept of all-optical technique that might dramatically increase the generation rate of random bits by using simultaneously multiple spectral channels with uncorrelated signals - somewhat similar to use of wave-division-multiplexing in communications. We propose to exploit the intrinsic nonlinear dynamics of extreme spectral broadening and supercontinuum (SC) generation in optical fibre, a process known to be often associated with non-deterministic fluctuations [2]. In this paper, we report proof-of concept results indicating that the fluctuations in highly nonlinear fibre SC generation can potentially be used for random number generation.

Vibration analysis of submerged rectangular microplates with distributed mass loading

This paper investigates the vibration characteristics of the coupling system of a microscale fluid-loaded rectangular isotropic plate attached to a uniformly distributed mass. Previous literature has, respectively, studied the changes in the plate vibration induced by an acoustic field or by the attached mass loading. This paper investigates the issue of involving these two types of loading simultaneously. Based on Lamb's assumption of the fluid-loaded structure and the Rayleigh–Ritz energy method, this paper presents an analytical solution for the natural frequencies and mode shapes of the coupling system. Numerical results for microplates with different types of boundary conditions have also been obtained and compared with experimental and numerical results from previous literature. The theoretical model and novel analytical solution are of particular interest in the design of microplate-based biosensing devices.

Transferring knowledge of manufacturing techniques within a subsidiary of a multi-national corporation

With the growth of the multi-national corporation (MNCs) has come the need to understand how parent companies transfer knowledge to, and manage the operations of, their subsidiaries. This is of particular interest to manufacturing companies transferring their operations overseas. Japanese companies in particular have been pioneering in the development of techniques such as Kaizen, and elements of the Toyota Production System (TPS) such as Kanban, which can be useful tools for transferring the ethos of Japanese manufacturing and maintaining quality and control in overseas subsidiaries. Much has been written about the process of transferring Japanese manufacturing techniques but much less is understood about how the subsidiaries themselves – which are required to make use of such techniques – actually acquire and incorporate them into their operations. This research therefore takes the perspective of the subsidiary in examining how knowledge of manufacturing techniques is transferred from the parent company within its surrounding (subsidiary). There is clearly a need to take a practice-based view to understanding how the local managers and operatives incorporate this knowledge into their working practices. A particularly relevant theme is how subsidiaries both replicate and adapt knowledge from parents and the circumstances in which replication or adaptation occurs. However, it is shown that there is a lack of research which takes an in-depth look at these processes from the perspective of the participants themselves. This is particularly important as much knowledge literature argues that knowledge is best viewed as enacted and learned in practice – and therefore transferred in person – rather than by the transfer of abstract and de-contextualised information. What is needed, therefore, is further research which makes an in-depth examination of what happens at the subsidiary level for this transfer process to occur. There is clearly a need to take a practice-based view to understanding how the local managers and operatives incorporate knowledge about manufacturing techniques into their working practices. In depth qualitative research was, therefore, conducted in the subsidiary of a Japanese multinational, Gambatte Corporation, involving three main manufacturing initiatives (or philosophies), namely 'TPS‘, 'TPM‘ and 'TS‘. The case data were derived from 52 in-depth interviews with project members, moderate-participant observations, and documentations and presented and analysed in episodes format. This study contributes to our understanding of knowledge transfer in relation to the approaches and circumstances of adaptation and replication of knowledge within the subsidiary, how the whole process is developed, and also how 'innovation‘ takes place. This study further understood that the process of knowledge transfer could be explained as a process of Reciprocal Provider-Learner Exchange that can be linked to the Experiential Learning Theory.

The economic impact of high growth start-ups:understanding the challenge for policy in the UK

Objectives The creation of more high-growth firms continues to be a key component of enterprise policy throughout the countries of the OECD. In the UK the developing enterprise policy framework highlights the importance of supporting businesses with growth potential. The difficulty, of course, is the ability of those delivering business support policies to accurately identify those businesses, especially at start-up, which will benefit from interventions and experiences an enhanced growth performance. This paper has a core objective of presenting new data on the number of high growth firms in the UK and providing an assessment of their economic significance. Approach This paper uses a specially created longitudinal firm-level database based on the Inter-Departmental Business Register (IDBR) held by the Office of National Statistics (ONS) for all private sector businesses in the UK for the period 1997-2008 to investigate the share of high-growth firms (including a sub-set of start-up more commonly referred to as gazelles) in successive cohorts of start-ups. We apply OECD definitions of high growth and gazelles to this database and are able to quantify for the first time their number (disaggregated by sector, region, size) and importance (employment and sales). Prior Work However, what is lacking at the core of this policy focus is any comprehensive statistical analysis of the scale and nature of high-growth firms in cohorts of new and established businesses. The evidence base in response to the question “Why do high-growth firms matter?” is surprisingly weak. Important work in this area has been initiated by Bartelsman et al., (2003),Hoffman and Jünge (2006) and Henreksen and Johansson (2009) but to date work in the UK has been limited (BERR, 2008b). Results We report that there are ~11,500 high growth firms in the UK in both 2005 and 2008. The share of high growth start-ups in the UK in 2005 (6.3%) was, contrary to the widely held perception in policy circles, higher than in the United States (5.2%). Of particular interest in the analysis are the growth trajectories (pattern of growth) of these firms as well as the extent to which they are restricted to technology-based or knowledge-based sectors. Implications and Value Using hitherto unused population data for the first time we have answered a fundamental research and policy question on the number and scale of high growth firms in the UK. We draw the conclusion that this ‘rare’ event does not readily lend itself to policy intervention on the grounds that the significant effort needed to identify such businesses ex ante would appear unjustified even if it was possible.

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors.

Transferring knowledge of manufacturing techniques in multinational corporations:preliminary findings

With the growth of the multinational corporation (MNC) has come the need to understand how parent companies transfer knowledge to, and manage the operations of, their subsidiaries. This is of particular interest to manufacturing companies transferring their operations overseas. Japanese companies in particular have been pioneering in this regard, with techniques such as the Toyota Production System (TPS) for transferring the ethos of Japanese manufacturing and maintaining quality and control in overseas subsidiaries. A great deal has been written about the process of transferring Japanese manufacturing techniques, but much less is understood about how the subsidiaries themselves, which are required to make use of such techniques, actually acquire and incorporate them into their operations. The research on which this paper is based therefore examines how, from the perspective of the subsidiary, knowledge of manufacturing techniques is transferred from the parent company. There is clearly a need to take a practice-based view to understanding how the local managers and operatives incorporate knowledge about manufacturing techniques into their working practices. In-depth qualitative research was, therefore, conducted in the subsidiary of a Japanese multinational, Denso Corporation, involving three main manufacturing initiatives (or philosophies), namely ‘TPS’, ‘TPM’ and ‘TS’. The case data were derived from 52 in-depth interviews with project members, moderate participant observations, and documentations. The aim of this paper is to present the preliminary findings from the case analyses. The research contributes to our understanding of knowledge transfer in relation to the circumstances of the selection between adaptation and replication of knowledge in the subsidiary from its parent. In particular this understanding relates to transfer across different flows and levels in the organisational hierarchy, how the whole process is managed, and also how modification takes place.

We want drama! The effect of online conflict on social capital in online communities of consumption

Online communities (OC) are an expanding social phenomenon gaining increasing interest from marketing practitioners. Community managers thus aim to increase OCs’ social capital. Diversity of individuals interacting in OCs provokes a lot of conflict. However, the influence of online conflict on OCs’ social capital is not clear as research indicates both positive and negative effects. The research aims to explain these contradictory effects by conceptualizing conflict as drama and developing a typology of online conflict. Based on netnographic investigations of a forum, four types of conflicts are thus distinguished depending on valence of emotions and the type of members involved. The research contributes to literature on OC dynamics and is of particular interest for community managers working in any company or organization.

Can certain genotypes predispose to poor asthma control in children? A pharmacogenetic study of 9 candidate genes in children with difficult asthma

Objective - We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control. Methods - A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma. Key Results - The results indicated that LTA4H A-9188>G, TNFα G-308>A and IL-4Rα A1727>G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p<0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Rα A1199>C, IL-4Rα T1570>C and IL-4Rα A1727>G and CA haplotype of TNFα C-863>A and TNFα G-308>A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively). Conclusions and Clinical Relevance - The study revealed multiple SNPs and haplotypes in LTA4H, TNFα and IL4-Rα genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A-9188>G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit.