A biological-inspired support frame for an artificial cornea

Bilateral corneal blindness represents a quarter of the total blind, world-wide. The artificial cornea in assorted forms, was developed to replace opaque non-functional corneas and to return sight in otherwise hopeless cases that were not amenable to corneal grafts; believed to be 2% of corneal blind. Despite technological advances in materials design and tissue engineering no artificial cornea has provided absolute, long-term success. Formidable problems exist, due to a combination of unpredictable wound healing and unmanageable pathology. To have a solid guarantee of reliable success an artificial cornea must possess three attributes: an optical window to replace the opaque cornea; a strong, long term union to surrounding ocular tissue; and the ability to induce desired host responses. A unique artificial cornea possesses all three functional attributes- the Osteo-odonto-keratoprosthesis (OOKP). The OOKP has a high success rate and can survive for up to twenty years, but it is complicated both in structure and in surgical procedure; it is expensive and not universally available. The aim of this project was to develop a synthetic substitute for the OOKP, based upon key features of the tooth and bone structure. In doing so, surgical complexity and biological complications would be reduced. Analysis of the biological effectiveness of the OOKP showed that the structure of bone was the most crucial component for implant retention. An experimental semi-rigid hydroxyapatite framework was fabricated with a complex bone-like architecture, which could be fused to the optical window. The first method for making such a framework, was pressing and sintering of hydroxyapatite powders; however, it was not possible to fabricate a void architecture with the correct sizes and uniformity of pores. Ceramers were synthesised using alternative pore forming methods, providing for improved mechanical properties and stronger attachment to the plastic optical window. Naturally occurring skeletal structures closely match the structural features of all forms of natural bone. Synthetic casts were fabricated using the replamineform process, of desirable natural artifacts, such as coral and sponges. The final method of construction by-passed ceramic fabrication in favour of pre-formed coral derivatives and focused on methods for polymer infiltration, adhesion and fabrication. Prototypes were constructed and evaluated; a fully penetrative synthetic OOKP analogue was fabricated according to the dimensions of the OOKP. Fabrication of the cornea shaped OOKP synthetic analogue was also attempted.

The West Midlands road transport industry

The object of this project was to identify those elements of management practice which characterised firms in the West Midlands Road Transport Industry. The object being to establish the contents of what might be termed a management policy portfolio for growth. The First Phase was the review of those factors which were generally accepted as having an influence on the success rate of transport firms in order to ascertain if they explained observed patterns. Secondly, if this were not the case, to instigate a field work study to isolate those policies which were associated with growth organizations. Investigation of the vehicle movements for the entire West Midlands Fleet over a complete licence cycle suggested that conventional explanations could not fully account for the observed patterns. To carry out the second phase of the study a sample of growth firms were visited in order to measure their attitudes on a range of factors hypothesised to affect growth. Field data were analysed to establish management activities over a wide range of areas and the results further investigated through a Principal Components and Cluster Analysis programme. The outcome of the study indicates that some past attitudes on the skills and attitudes of transport managers may have to be re-examined. As a result, the project produced a new classification of road transport firms based not on the conventional categories of long and short haul, or the types of traffics carried, but on the marketing policies and management skills employed within the organization.

Objective and psychophysical studies of infant visual development

Distortion or deprivation of vision during an early `critical' period of visual development can result in permanent visual impairment which indicates the need to identify and treat visually at-risk individuals early. A significant difficulty in this respect is that conventional, subjective methods of visual acuity determination are ineffective before approximately three years of age. In laboratory studies, infant visual function has been quantified precisely, using objective methods based on visual evoked potentials (VEP), preferential looking (PL) and optokinetic nystagmus (OKN) but clinical assessment of infant vision has presented a particular difficulty. An initial aim of this study was to evaluate the relative clinical merits of the three techniques. Clinical derivatives were devised, the OKN method proved unsuitable but the PL and VEP methods were evaluated in a pilot study. Most infants participating in the study had known ocular and/or neurological abnormalities but a few normals were included for comparison. The study suggested that the PL method was more clinically appropriate for the objective assessment of infant acuity. A study of normal visual development from birth to one year was subsequently conducted. Observations included cycloplegic refraction, ophthalmoscopy and preferential looking visual acuity assessment using horizontally and vertically oriented square wave gratings. The aims of the work were to investigate the efficiency and sensitivity of the technique and to study possible correlates of visual development. The success rate of the PL method varied with age; 87% of newborns and 98% of infants attending follow-up successfully completed at least one acuity test. Below two months monocular acuities were difficult to secure; infants were most testable around six months. The results produced were similar to published data using the acuity card procedure and slightly lower than, but comparable with acuity data derived using extended PL methods. Acuity development was not impaired in infants found to have retinal haemorrhages as newborns. A significant relationship was found between newborn binocular acuity and anisometropia but not with other refractive findings. No strong or consistent correlations between grating acuity and refraction were found for three, six or twelve months olds. Improvements in acuity and decreases in levels of hyperopia over the first week of life were suggestive of recovery from minor birth trauma. The refractive data was analysed separately to investigate the natural history of refraction in normal infants. Most newborns (80%) were hyperopic, significant astigmatism was found in 86% and significant anisometropia in 22%. No significant alteration in spherical equivalent refraction was noted between birth and three months, a significant reduction in hyperopia was evident by six months and this trend continued until one year. Observations on the astigmatic component of the refractive error revealed a rather erratic series of changes which would be worthy of further investigation since a repeat refraction study suggested difficulties in obtaining stable measurements in newborns. Astigmatism tended to decrease between birth and three months, increased significantly from three to six months and decreased significantly from six to twelve months. A constant decrease in the degree of anisometropia was evident throughout the first year. These findings have implications for the correction of infantile refractive error.

Optimization of protein crystallization:the OptiCryst project

Protein crystallization has gained a new strategic and commercial relevance in the postgenomic era due to its pivotal role in structural genomics. Producing high quality crystals has always been a bottleneck to efficient structure determination, and this problem is becoming increasingly acute. This is especially true for challenging, therapeutically important proteins that typically do not form suitable crystals. The OptiCryst consortium has focused on relieving this bottleneck by making a concerted effort to improve the crystallization techniques usually employed, designing new crystallization tools, and applying such developments to the optimization of target protein crystals. In particular, the focus has been on the novel application of dual polarization interferometry (DPI) to detect suitable nucleation; the application of in situ dynamic light scattering (DLS) to monitor and analyze the process of crystallization; the use of UV-fluorescence to differentiate protein crystals from salt; the design of novel nucleants and seeding technologies; and the development of kits for capillary counterdiffusion and crystal growth in gels. The consortium collectively handled 60 new target proteins that had not been crystallized previously. From these, we generated 39 crystals with improved diffraction properties. Fourteen of these 39 were only obtainable using OptiCryst methods. For the remaining 25, OptiCryst methods were used in combination with standard crystallization techniques. Eighteen structures have already been solved (30% success rate), with several more in the pipeline.

AstonCAT-plus:an efficient specialist for the TAC market design tournament

This paper describes the strategies used by AstonCAT-Plus, the post-tournament version of the specialist designed for the TAC Market Design Tournament 2010. It details how AstonCATPlus accepts shouts, clears market, sets transaction prices and charges fees. Through empirical evaluation, we show that AstonCAT-Plus not only outperforms AstonCAT (tournament version) significantly but also achieves the second best overall score against some top entrants of the competition. In particular, it achieves the highest allocative efficiency, transaction success rate and average trader profit among all the specialists in our controlled experiments.

Neuronal network dynamics during epileptogenesis in the medial temporal lobe

Epilepsy is one of the most common neurological disorders, a large fraction of which is resistant to pharmacotherapy. In this light, understanding the mechanisms of epilepsy and its intractable forms in particular could create new targets for pharmacotherapeutic intervention. The current project explores the dynamic changes in neuronal network function in the chronic temporal lobe epilepsy (TLE) in rat and human brain in vitro. I focused on the process of establishment of epilepsy (epileptogenesis) in the temporal lobe. Rhythmic behaviour of the hippocampal neuronal networks in healthy animals was explored using spontaneous oscillations in the gamma frequency band (SγO). The use of an improved brain slice preparation technique resulted in the natural occurence (in the absence of pharmacological stimulation) of rhythmic activity, which was then pharmacologically characterised and compared to other models of gamma oscillations (KA- and CCh-induced oscillations) using local field potential recording technique. The results showed that SγO differed from pharmacologically driven models, suggesting higher physiological relevance of SγO. Network activity was also explored in the medial entorhinal cortex (mEC), where spontaneous slow wave oscillations (SWO) were detected. To investigate the course of chronic TLE establishment, a refined Li-pilocarpine-based model of epilepsy (RISE) was developed. The model significantly reduced animal mortality and demonstrated reduced intensity, yet high morbidy with almost 70% mean success rate of developing spontaneous recurrent seizures. We used SγO to characterize changes in the hippocampal neuronal networks throughout the epileptogenesis. The results showed that the network remained largely intact, demonstrating the subtle nature of the RISE model. Despite this, a reduction in network activity was detected during the so-called latent (no seizure) period, which was hypothesized to occur due to network fragmentation and an abnormal function of kainate receptors (KAr). We therefore explored the function of KAr by challenging SγO with kainic acid (KA). The results demonstrated a remarkable decrease in KAr response during the latent period, suggesting KAr dysfunction or altered expression, which will be further investigated using a variety of electrophysiological and immunocytochemical methods. The entorhinal cortex, together with the hippocampus, is known to play an important role in the TLE. Considering this, we investigated neuronal network function of the mEC during epileptogenesis using SWO. The results demonstrated a striking difference in AMPAr function, with possible receptor upregulation or abnormal composition in the early development of epilepsy. Alterations in receptor function inevitably lead to changes in the network function, which may play an important role in the development of epilepsy. Preliminary investigations were made using slices of human brain tissue taken following surgery for intratctable epilepsy. Initial results showed that oscillogenesis could be induced in human brain slices and that such network activity was pharmacologically similar to that observed in rodent brain. Overall, our findings suggest that excitatory glutamatergic transmission is heavily involved in the process of epileptogenesis. Together with other types of receptors, KAr and AMPAr contribute to epilepsy establishment and may be the key to uncovering its mechanism.

EpiJen:a server for multistep T cell epitope prediction

Background - The main processing pathway for MHC class I ligands involves degradation of proteins by the proteasome, followed by transport of products by the transporter associated with antigen processing (TAP) to the endoplasmic reticulum (ER), where peptides are bound by MHC class I molecules, and then presented on the cell surface by MHCs. The whole process is modeled here using an integrated approach, which we call EpiJen. EpiJen is based on quantitative matrices, derived by the additive method, and applied successively to select epitopes. EpiJen is available free online. Results - To identify epitopes, a source protein is passed through four steps: proteasome cleavage, TAP transport, MHC binding and epitope selection. At each stage, different proportions of non-epitopes are eliminated. The final set of peptides represents no more than 5% of the whole protein sequence and will contain 85% of the true epitopes, as indicated by external validation. Compared to other integrated methods (NetCTL, WAPP and SMM), EpiJen performs best, predicting 61 of the 99 HIV epitopes used in this study. Conclusion - EpiJen is a reliable multi-step algorithm for T cell epitope prediction, which belongs to the next generation of in silico T cell epitope identification methods. These methods aim to reduce subsequent experimental work by improving the success rate of epitope prediction.

The influence of organizational and national culture on new product performance

The authors conduct a meta-analysis on the combined influence of organizational and national culture on new product performance. For this purpose, they refer to the effectiveness of value congruency and develop a conceptual model describing the fit between organizational culture types as suggested by the competing values framework and national culture, as described by Hofstede's cultural dimensions. The meta-analysis is based on 489 effect sizes taken from 123 manuscripts. The findings show that organizations with a market culture show the highest new product performance, while hierarchy-type organizations show the lowest performance. The influence of national culture variables supports the effect of value congruency, and shows that in individualistic cultures the impact of a clan culture decreases, the impact of an adhocracy culture type decreases with uncertainty avoidance, and the influence of a hierarchy culture type increases with power distance. The superior effect of a market culture type can be matched by other organizational orientations, but in particular national cultures only. The combined findings underline the importance for firms that seek to improve the success rate of new products on international markets to consider the fit of a national culture with a firm's organizational culture.

Use of Google as a tool to aid diagnosis by optometry students

Background: Previous work has shown that medical problems can be diagnosed by practitioners using Google. The aim of this study was to determine whether optometry students would benefit from using Google when diagnosing eye diseases. Methods: Participants were given symptoms and signs and instructed to list three key words and use them to search Aston University e-Library and Google UK. Results: Aston University e-Library only search resulted in correct diagnosis in 16 of 60 simulated cases. Aston e-Library plus Google search resulted in correct diagnosis in 31 of 60 simulated cases. Conclusion: Google is a useful aid to help optometry students improve their success rate when diagnosing eye conditions.

Self-adaptive probabilistic roadmap generation for intelligent virtual agents

Agents inhabiting large scale environments are faced with the problem of generating maps by which they can navigate. One solution to this problem is to use probabilistic roadmaps which rely on selecting and connecting a set of points that describe the interconnectivity of free space. However, the time required to generate these maps can be prohibitive, and agents do not typically know the environment in advance. In this paper we show that the optimal combination of different point selection methods used to create the map is dependent on the environment, no point selection method dominates. This motivates a novel self-adaptive approach for an agent to combine several point selection methods. The success rate of our approach is comparable to the state of the art and the generation cost is substantially reduced. Self-adaptation therefore enables a more efficient use of the agent's resources. Results are presented for both a set of archetypal scenarios and large scale virtual environments based in Second Life, representing real locations in London.

An analysis of penalty kicks in elite football post 1997

The penalty kick in football is a seemingly simplistic play; however, it has increased in complexity since 1997 when the rules changed allowing goalkeepers to move laterally along their goal line before the ball was kicked. Prior to 1997 goalkeepers were required to remain still until the ball was struck. The objective of this study was to determine the importance of the penalty kick in the modern game of football. A retrospective study of the 2002, 2006 and 2010 World Cup and the 2000, 2004 and 2008 European Championship tournaments was carried out, assessing the importance of the penalty kick in match play and shootouts and the effect of the time of the game on the shooter's success rate. This study demonstrated the conversion rate of penalties was 73% in shootouts and 68% in match play. Significantly more penalties were awarded late in the game: twice as many penalties in the second half than the first and close to four times as many in the fourth quarter vs. the first. Teams awarded penalty kicks during match play won 52%, drew 30% and lost 18% of the time; chances of winning increased to 61% if the penalty was scored, but decreased to 29% if missed. Teams participating in either the World Cup or European Championship final match had roughly a 50% chance of being involved in a penalty shootout during the tournament. Penalty shots and their outcome significantly impact match results in post 1997 football.

The management of posterior vitreous detachment by an optometrist

Acute posterior vitreous detachment (PVD) is the most common cause of retinal detachment. The management of this condition can be variable and often undue reliance is placed upon associated signs and symptoms which can be a poor indicator of pathology. Optometrists undertake a number of extended roles, however involvement in vitreo-retinal sub-specialities appears to be limited. One objective was to directly compare an optometrist and ophthalmologist in the assessment of patients with PVD, for this a high level of agreement was found (95% sensitivity, 99% specificity, 0.94 kappa). A review of 1107 patients diagnosed with acute PVD that were re-evaluated in a PVD clinic a few weeks later was undertaken to determine whether such reviews are necessary. One-fifth of patients were found to have conditions undiagnosed at the initial assessment, overall 4% of patients had retinal breaks when examined in the PVD clinic and a total of 7% required further intervention. The sensitivity of fundus examination with +90D and 3-mirror lenses was 85-88% for detecting retinal breaks and 7-85% for pigment in the anterior vitreous for the presence of retinal breaks. Therefore patients with acute PVD should be examined by indirect ophthalmoscopy with indentation at the onset of PVD and 4-6 weeks later. The treatment of retinal breaks with laser retinopexy is performed by ophthalmologists with a primary success rate 54-85%. In a pioneering development, an optometrist undertaking this role achieved a comparable primary success rate (79%). Mid-vitreous opacities associated with PVD are described, and noted in 100% of eyes with PVD. The recognition of this sign is important in the diagnosis of PVD and retinal breaks. The importance of diagnostic imaging is also demonstrated, however the timing in relation to onset may be vital.