• Learning adaptation knowledge to improve case-based reasoning.

      Craw, S.; Wiratunga, N.; Rowe, Raymond C. (2006)
      Case-Based Reasoning systems retrieve and reuse solutions for previously solved problems that have been encountered and remembered as cases. In some domains, particularly where the problem solving is a classification task, the retrieved solution can be reused directly. But for design tasks it is common for the retrieved solution to be regarded as an initial solution that should be refined to reflect the differences between the new and retrieved problems. The acquisition of adaptation knowledge to achieve this refinement can be demanding, despite the fact that the knowledge source of stored cases captures a substantial part of the problem-solving expertise. This paper describes an introspective learning approach where the case knowledge itself provides a source from which training data for the adaptation task can be assembled. Different learning algorithms are explored and the effect of the learned adaptations is demonstrated for a demanding component-based pharmaceutical design task, tablet formulation. The evaluation highlights the incremental nature of adaptation as a further reasoning step after nearest-neighbour retrieval. A new property-based classification to adapt symbolic values is proposed, and an ensemble of these property-based adaptation classifiers has been particularly successful for the most difficult of the symbolic adaptation tasks in tablet formulation.
    • Learning to use illumination gradients as an unambiguous cue to three dimensional shape

      Harding, Glen; Harris, J.M.; Bloj, Marina (2012)
      The luminance and colour gradients across an image are the result of complex interactions between object shape, material and illumination. Using such variations to infer object shape or surface colour is therefore a difficult problem for the visual system. We know that changes to the shape of an object can affect its perceived colour, and that shading gradients confer a sense of shape. Here we investigate if the visual system is able to effectively utilise these gradients as a cue to shape perception, even when additional cues are not available. We tested shape perception of a folded card object that contained illumination gradients in the form of shading and more subtle effects such as inter-reflections. Our results suggest that observers are able to use the gradients to make consistent shape judgements. In order to do this, observers must be given the opportunity to learn suitable assumptions about the lighting and scene. Using a variety of different training conditions, we demonstrate that learning can occur quickly and requires only coarse information. We also establish that learning does not deliver a trivial mapping between gradient and shape; rather learning leads to the acquisition of assumptions about lighting and scene parameters that subsequently allow for gradients to be used as a shape cue. The perceived shape is shown to be consistent for convex and concave versions of the object that exhibit very different shading, and also similar to that delivered by outline, a largely unrelated cue to shape. Overall our results indicate that, although gradients are less reliable than some other cues, the relationship between gradients and shape can be quickly assessed and the gradients therefore used effectively as a visual shape cue.
    • Lecozotan (SRA-333): a selective serotonin1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and possesses cognitive-enhancing properties.

      Harder, Josie A.; Womack, Matthew D.; Schechter, L.E.; Smith, D.L.; Childers, W.; Rosenzweig-Lipson, S.; Sukoff, S. (2005)
      Recent data has suggested that the 5-HT1A receptor is involved in cognitive processing. A novel 5- HT1A receptor antagonist, 4-cyano-N- [(2R)-[4- (2,3-dihydrobenzo [1,4] dioxin-5-yl) piperazin-1-yl] propyl]-N-pyridin-2-yl-benzamide hydrochloride (lecozotan), which has been characterized in multiple in vitro and in vivo pharmacologic assays as a drug to treat cognitive dysfunction, is reported. In vitro binding and intrinsic activity determinations demonstrated that lecozotan is a potent and selective 5-HT1A receptor antagonist. Using in vivo microdialysis, lecozotan (0.3 mg/kg sc) antagonized the decrease in hippocampal extracellular 5-HT induced by a challenge dose (0.3 mg/kg sc) of 8 OH-DPAT and had no effects alone at doses 10-fold higher. Lecozotan significantly potentiated the potassium chloride-stimulated release of glutamate and acetylcholine in the dentate gyrus of the hippocampus. Chronic administration of lecozotan did not induce 5-HT1A receptor tolerance or desensitization in a behavioral model indicative of 5- HT1A receptor function. In drug discrimination studies, lecozotan (0.01-1 mg/kg im) did not substitute for 8-OH-DPAT and produced a dose-related blockade of the 5-HT1A agonist discriminative stimulus cue. In aged rhesus monkeys, lecozotan produced a significant improvement in task performance efficiency at an optimal dose (1 mg/kg po). Learning deficits induced by the glutamatergic antagonist MK-801 (assessed by perceptually complex and visual spatial discrimination) and by specific cholinergic lesions of the hippocampus (assessed by visual spatial discrimination) were reversed by lecozotan (2 mg/kg im) in marmosets. The heterosynaptic nature of the effects of lecozotan imbues this compound with a novel mechanism of action directed at the biochemical pathologies underlying cognitive loss in AD.
    • Lessons learned from England’s Health Checks Programme: using qualitative research to identify and share best practice

      Ismail, Hanif; Kelly, S. (2015)
      This study aimed to explore the challenges and barriers faced by staff involved in the delivery of the National Health Service (NHS) Health Check, a systematic cardiovascular disease (CVD) risk assessment and management program in primary care. Data have been derived from three qualitative evaluations that were conducted in 25 General Practices and involved in depth interviews with 58 staff involved all levels of the delivery of the Health Checks. Analysis of the data was undertaken using the framework approach and findings are reported within the context of research and practice considerations. Findings indicated that there is no ‘one size fits all’ blueprint for maximising uptake although success factors were identified: evolution of the programme over time in response to local needs to suit the particular characteristics of the patient population; individual staff characteristics such as being proactive, enthusiastic and having specific responsibility; a supportive team. Training was clearly identified as an area that needed addressing and practitioners would benefit from CVD specific baseline training and refresher courses to keep them up to date with recent developments in the area. However there were other external factors that impinged on an individual’s ability to provide an effective service, some of these were outside the control of individuals and included cutbacks in referral services, insufficient space to run clinics or general awareness of the Health Checks amongst patients. The everyday experiences of practitioners who participated in this study suggest that overall, Health Check is perceived as a worthwhile exercise. But, organisational and structural barriers need to be addressed. We also recommend that clear referral pathways be in place so staff can refer patients to appropriate services (healthy eating sessions, smoking cessation, and exercise referrals). Local authorities need to support initiatives that enable data sharing and linkage so that GP Practices are informed when patients take up services such as smoking cessation or alcohol harm reduction programmes run by social services.
    • Letter to the Editor concerning “A systematic review of controlled trials on visual stress using intuitive overlays or colorimeter"

      Griffiths, P.G.; Taylor, R.H.; Henderson, L.M.; Barrett, Brendan T. (2017)
      We read with interest the review written by Evans and Allen, and published in the Journal of Optometry, in July, 2016.
    • Letter to the Editor: Authors' response.

      Griffiths, P.G.; Taylor, R.H.; Henderson, L.M.; Barrett, Brendan T. (2017)
      We thank Professors Evans and Wilkins for their interest in our systematic review.(1) We have reached the same conclusion as previous systematic reviews published in 2008(2) and 2014(3) and a review prepared for the New Zealand Ministry for Health in 2009.(4) Even the ‘alternative systematic review’ prepared by Professors Evans and Allen about which we have significant misgivings concludes that ‘larger and rigorous randomised controlled trials of interventions for visual stress are required’.(5)
    • Levels of state and trait anxiety in patients referred to ophthalmology by primary care clinicians: a cross sectional study

      Davey, Christopher J.; Harley, C.; Elliott, David B. (2013-06-13)
      Purpose There is a high level of over-referral from primary eye care leading to significant numbers of people without ocular pathology (false positives) being referred to secondary eye care. The present study used a psychometric instrument to determine whether there is a psychological burden on patients due to referral to secondary eye care, and used Rasch analysis to convert the data from an ordinal to an interval scale. Design Cross sectional study. Participants and Controls 322 participants and 80 control participants. Methods State (i.e. current) and trait (i.e. propensity to) anxiety were measured in a group of patients referred to a hospital eye department in the UK and in a control group who have had a sight test but were not referred. Response category analysis plus infit and outfit Rasch statistics and person separation indices were used to determine the usefulness of individual items and the response categories. Principal components analysis was used to determine dimensionality. Main Outcome Measure Levels of state and trait anxiety measured using the State-Trait Anxiety Inventory. Results State anxiety scores were significantly higher in the patients referred to secondary eye care than the controls (p<0.04), but similar for trait anxiety (p>0.1). Rasch analysis highlighted that the questionnaire results needed to be split into “anxiety-absent” and “anxiety-present” items for both state and trait anxiety, but both subscales showed the same profile of results between patients and controls. Conclusions State anxiety was shown to be higher in patients referred to secondary eye care than the controls, and at similar levels to people with moderate to high perceived susceptibility to breast cancer. This suggests that referral from primary to secondary eye care can result in a significant psychological burden on some patients.
    • Lexical decisions in adults with low and high susceptibility to pattern-related visual stress: a preliminary investigation

      Gilchrist, James M.; Allen, P.M. (2015-04-14)
      Pattern-related visual stress (PRVS) is a form of sensory hypersensitivity that some people experience when viewing high contrast repeating patterns, notably alternating dark and light stripes. Those susceptible to PRVS typically have a strong aversion to such stimuli, and this is often accompanied by experiences of visual discomfort and disturbance. The patterns most likely to elicit symptoms of PRVS have a square-wave grating configuration of spatial frequency ~3 cycles/degree. Such stimuli are characteristic of printed text in which lines of words and the spaces between them present a high contrast grating-like stimulus. Consequently, much printed reading material has the potential to elicit PRVS that may impair reading performance, and this problem appears to be common in individuals with reading difficulties including dyslexia. However, the manner in which PRVS affects reading ability is unknown. One possibility is that the early sensory visual stress may interfere with the later cognitive word recognition stage of the reading process, resulting in reading performance that is slower and/or less accurate. To explore the association of PRVS with word recognition ability, lexical decision performance (speed and accuracy) to words and pronounceable non-words was measured in two groups of adults, having low and high susceptibility to PRVS. Results showed that lexical decisions were generally faster but less accurate in high-PRVS, and also that high-PRVS participants made decisions significantly faster for words than for non-words, revealing a strong lexicality effect that was not present in low-PRVS. These findings are novel and, as yet, unconfirmed by other studies.
    • Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury

      Mardaryev, Andrei N.; Meier, N.; Poterlowicz, Krzysztof; Sharov, A.A.; Sharova, T.Y.; Ahmed, Mohammed I.; Rapisarda, Valentina; Lewis, Christopher J.; Fessing, Michael Y.; Ruenger, T.M.; et al. (2011)
      The Lhx2 transcription factor plays essential roles in morphogenesis and patterning of ectodermal derivatives as well as in controlling stem cell activity. Here, we show that during murine skin morphogenesis, Lhx2 is expressed in the hair follicle (HF) buds, whereas in postnatal telogen HFs Lhx2(+) cells reside in the stem cell-enriched epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5). Remarkably, Lhx2(+) cells represent the vast majority of cells in the bulge and secondary hair germ that proliferate in response to skin injury. This is functionally important, as wound re-epithelization is significantly retarded in heterozygous Lhx2 knockout (+/-) mice, whereas anagen onset in the HFs located closely to the wound is accelerated compared with wild-type mice. Cell proliferation in the bulge and the number of Sox9(+) and Tcf4(+) cells in the HFs closely adjacent to the wound in Lhx2(+/-) mice are decreased in comparison with wild-type controls, whereas expression of Lgr5 and cell proliferation in the secondary hair germ are increased. Furthermore, acceleration of wound-induced anagen development in Lhx2(+/-) mice is inhibited by administration of Lgr5 siRNA. Finally, Chip-on-chip/ChIP-qPCR and reporter assay analyses identified Sox9, Tcf4 and Lgr5 as direct Lhx2 targets in keratinocytes. These data strongly suggest that Lhx2 positively regulates Sox9 and Tcf4 in the bulge cells, and promotes wound re-epithelization, whereas it simultaneously negatively regulates Lgr5 in the secondary hair germ and inhibits HF cycling. Thus, Lhx2 operates as an important regulator of epithelial stem cell activity in the skin response to injury.
    • The lichen flora of Hull, with particular reference to zonal distribution and environmental monitoring

      Seaward, Mark R.D. (2004)
      The role of lichens as environmental monitors is widely recognised. Not only are they valuable as indicators of habitat stability and enyironmental continuity, but they are also effectiye in monitoring environmental quality. more particularly air and soil (and more recently water) pollution. In the past. the main role of lichens in this context has been to monitor sulphur dioxide air pollution. especially stable and rising levels (Seaward 1993). Howeyer, it has also been shown that lichens arc effective monitors of falling levels of gaseous sulphur dioxide and indeed of other pollutants. some of which are manifesting themselves as a consequence of the reduction in the former; of particular interest in this respect is the use of lichens to detect and determine the extent of qualitative changes in air pollution such as the impact of acid rain and hypertrophication (Seaward 1997: Seaward & Coppins 2(04).
    • Lichen flora of the West Yorkshire conurbation - Supplement VII (1999-2004)

      Seaward, Mark R.D.; Henderson, A.; Hitch, C.J.B (2005)
    • Lichenological exploration of Algeria: historical overview and annotated bibliography, 1799-2013

      Amrani, S.; Nacer, A.; Noureddine, N.E.; Seaward, Mark R.D. (2015-04)
      Despite more than two centuries of almost uninterrupted surveys and studies of Algerian lichenology, the history and lichen diversity of Algeria are still poorly understood. During the preparation of a forthcoming checklist of Algerian lichens it was considered necessary to provide the present historical overview of lichenological exploration of the country from 1799 to 2013, supported by a reasonably comprehensive annotated bibliography of 171 titles.
    • Lichens as agents of biodeterioration

      Seaward, Mark R.D. (2015)
      One of the major roles lichens play in shaping the natural world, both physically and biologically, is as agents in soil development: formerly considered only in a geological context, recent research has shown that they are capable of biodeteriorating stone substrata within a relatively short timescale. Chemical alteration of the substratum is achieved by the disruptive action of many species, particularly those capable of producing an oxalate at the thallus–substratum interface . The oxalate contributes significantly to the bulk and composition of the thallus itself and persists as an obvious encrustation after the lichen’s death. In the past, these disfiguring oxalate residues on ancient monuments have been variously interpreted as resulting from former mechanical/chemical renovation treatments, atmospheric pollution , and climatic weathering. The origin and nature of oxalate accretions, the factors involved in pedogenesis , and the development of lichen mosaics are reviewed. Aesthetic disfigurement versus physical damage to stonework is considered, and various aspects of stonework conservation are discussed.
    • Life in the Sabkha: Raman Spectroscopy of Halotrophic Extremophiles of Relevance to Planetary Exploration

      Edwards, Howell G.M.; Mohsin, M.A.; Sadhooni, F.N.; Hassan, N.K.N.; Munshi, Tasnim (2006)
      The Raman spectroscopic biosignatures of halotrophic cyanobacterial extremophiles from sabkha evaporitic saltpans are reported for the first time and ideas about the possible survival strategies in operation have been forthcoming. The biochemicals produced by the cyanobacteria which colonise the interfaces between large plates of clear selenitic gypsum, halite, and dolomitized calcium carbonates in the centre of the salt pans are identifiably different from those which are produced by benthic cyanobacterial mats colonising the surface of the salt pan edges in the intertidal zone. The prediction that similar geological formations would have been present on early Mars and which could now be underlying the highly peroxidised regolith on the surface of the planet has been confirmed by recent satellite observations from Mars orbit and by localised traverses by robotic surface rovers. The successful adoption of miniaturised Raman spectroscopic instrumentation as part of a scientific package for detection of extant life or biomolecular traces of extinct life on proposed future Mars missions will depend critically on interpretation of data from terrestrial Mars analogues such as sabkhas, of which the current study is an example.
    • Limitations of correcting spherical aberration with aspheric intraocular lenses.

      Dietze, Holger H.; Cox, Michael J. (2005)
      Aspheric intraocular lenses (IOLs) are designed to correct spherical aberration in pseudophakic eyes. We predict the benefit from correcting spherical aberration based on simulations and aberrometry of pseudophakic eyes implanted with spherical IOLs. METHODS Ray tracing was performed through a model eye with an equi-biconvex spherical IOL and with a spherical aberration-correcting aspheric IOL. The IOLs were increasingly tilted and/or displaced, and the resulting transverse aberrations of 169 rays were transformed into Zernike coefficients for different pupil sizes. The benefit from correcting spherical aberration at individual mesopic pupils was investigated by canceling in the sets of Zernike coefficients for 41 eyes implanted with a spherical IOL. RESULTS Both the model eye and the real eye data predict that age-related miosis reduces spherical aberration in the eye implanted with a spherical IOL to approximately 1/3 of the spherical aberration at a 6-mm pupil. A reduction of similar magnitude occurs when spherical aberration-induced non-paraxial defocus is corrected by a spectacle lens. For natural mesopic pupils, canceling the Zernike coefficient improved the objective image quality at a rate similar to changing defocus by 0.05 diopters. Average centration and tilt levels diminish the lead of aspheric IOLs over spherical IOLs, depending on the direction of decentration. CONCLUSIONS The benefit from correcting spherical aberration in a pseudophakic eye is limited for some or all of the following reasons: wearing glasses, age-related miosis, tilt and decentration of IOL, small contribution of spherical aberration to all aberrations, and intersubject variability
    • A Limited Role for Suppression in the Central Field of Individuals with Strabismic Amblyopia.

      Barrett, Brendan T.; Panesar, Gurvinder K.; Scally, Andy J.; Pacey, Ian E. (2012)
      Background: Although their eyes are pointing in different directions, people with long-standing strabismic amblyopia typically do not experience double-vision or indeed any visual symptoms arising from their condition. It is generally believed that the phenomenon of suppression plays a major role in dealing with the consequences of amblyopia and strabismus, by preventing images from the weaker/deviating eye from reaching conscious awareness. Suppression is thus a highly sophisticated coping mechanism. Although suppression has been studied for over 100 years the literature is equivocal in relation to the extent of the retina that is suppressed, though the method used to investigate suppression is crucial to the outcome. There is growing evidence that some measurement methods lead to artefactual claims that suppression exists when it does not. Methodology/Results: Here we present the results of an experiment conducted with a new method to examine the prevalence, depth and extent of suppression in ten individuals with strabismic amblyopia. Seven subjects (70%) showed no evidence whatsoever for suppression and in the three individuals who did (30%), the depth and extent of suppression was small. Conclusions: Suppression may play a much smaller role in dealing with the negative consequences of strabismic amblyopia than previously thought. Whereas recent claims of this nature have been made only in those with micro-strabismus our results show extremely limited evidence for suppression across the central visual field in strabismic amblyopes more generally. Instead of suppressing the image from the weaker/deviating eye, we suggest the visual system of individuals with strabismic amblyopia may act to maximise the possibilities for binocular co-operation. This is consistent with recent evidence from strabismic and amblyopic individuals that their binocular mechanisms are intact, and that, just as in visual normals, performance with two eyes is better than with the better eye alone in these individuals.
    • Limits and possibilities in the geolocation of humans using multiple isotope ratios (H, O, N, C) of hair from east coast cities of the USA

      Reynard, L.M.; Burt, N.; Koon, Hannah E.C.; Tuross, N. (2016-07)
      We examined multiple natural abundance isotope ratios of human hair to assess biological variability within and between geographic locations and, further, to determine how well these isotope values predict location of origin. Sampling locations feature differing seasonality and mobile populations as a robust test of the method. Serially-sampled hair from Cambridge, MA, USA, shows lower δ2 H and δ18 O variability over a one-year time course than model-predicted precipitation isotope ratios, but exhibits considerable differences between individuals. Along a ∼13° northsouth transect in the eastern USA (Brookline, MA, 42.3 ° N, College Park, MD, 39.0 ° N, and Gainesville, FL, 29.7 ° N) δ18 O in human hair shows relatively greater differences and tracks changes in drinking water isotope ratios more sensitively than δ2 H. Determining the domicile of humans using isotope ratios of hair can be confounded by differing variability in hair δ18 O and δ2 H between locations, differential incorporation of H and O into this protein and, in some cases, by tap water δ18 O and δ2 H that differ significantly from predicted precipitation values. With these caveats, randomly chosen people in Florida are separated from those in the two more northerly sites on the basis of the natural abundance isotopes of carbon, nitrogen, hydrogen, and oxygen.
    • Linear combination methods for prediction of drug skin permeation

      Scheler, S.; Fahr, A.; Liu, Xiangli (2015-01)
      Many in-vitro methods for prediction of skin permeability have been reported in literature. Cerasome electrokinetic chromatography is one of the most sophisticated approaches representing a maximum level of similarity to the lipid phase of the stratum corneum. One goal of this study was to investigate the affinity pattern of Cerasome and to compare it with the permeability profile of human skin. Another purpose was to study the applicability of Hansen solubility parameters for modelling skin permeation and to investigate the predictive and explanatory potential of this method. Visualisation in Hansen diagrams revealed very similar profiles of Cerasome electrokinetic chromatography retention factors and skin permeability coefficients. In both cases, the characteristic pattern with two clusters of highly retained or highly permeable substances could be shown to be mainly caused by two groups of compounds, one of them with high affinity to ceramides, fatty acids and lecithin and the other being more affine to cholesterol. If based on a sufficiently comprehensive experimental dataset, model-independent predictions of skin permeability data using three-component Hansen solubility parameters are able to achieve similar accuracy as calculations made with an Abraham linear free energy relationship model in which the compounds are characterized by seven physicochemical descriptors.