• Label-Free Electrochemical Sensor for Rapid Bacterial Pathogen Detection Using Vancomycin-Modified Highly Branched Polymers

      Schulze, H.; Wilson, H.; Cara, I.; Carter, Steven; Dyson, Edward N.; Elangovan, R.; Rimmer, Stephen; Bachmann, T.T. (MDPI, 2021-03-08)
      Rapid point of care tests for bacterial infection diagnosis are of great importance to reduce the misuse of antibiotics and burden of antimicrobial resistance. Here, we have successfully combined a new class of non-biological binder molecules with electrochemical impedance spectroscopy (EIS)-based sensor detection for direct, label-free detection of Gram-positive bacteria making use of the specific coil-to-globule conformation change of the vancomycin-modified highly branched polymers immobilized on the surface of gold screen-printed electrodes upon binding to Gram-positive bacteria. Staphylococcus carnosus was detected after just 20 min incubation of the sample solution with the polymer-functionalized electrodes. The polymer conformation change was quantified with two simple 1 min EIS tests before and after incubation with the sample. Tests revealed a concentration dependent signal change within an OD600 range of Staphylococcus carnosus from 0.002 to 0.1 and a clear discrimination between Gram-positive Staphylococcus carnosus and Gram-negative Escherichia coli bacteria. This exhibits a clear advancement in terms of simplified test complexity compared to existing bacteria detection tests. In addition, the polymer-functionalized electrodes showed good storage and operational stability.
    • Language-guided visual processing affects reasoning: the role of referential and spatial anchoring

      Dimitru, M.L.; Joergensen, G.H.; Cruickshank, Alice G.; Altmann, G.T.M. (2013)
      Language is more than a source of information for accessing higher-order conceptual knowledge. Indeed, language may determine how people perceive and interpret visual stimuli. Visual processing in linguistic contexts, for instance, mirrors language processing and happens incrementally, rather than through variously-oriented fixations over a particular scene. The consequences of this atypical visual processing are yet to be determined. Here, we investigated the integration of visual and linguistic input during a reasoning task. Participants listened to sentences containing conjunctions or disjunctions (Nancy examined an ant and/or a cloud) and looked at visual scenes containing two pictures that either matched or mismatched the nouns. Degree of match between nouns and pictures (referential anchoring) and between their expected and actual spatial positions (spatial anchoring) affected fixations as well as judgments. We conclude that language induces incremental processing of visual scenes, which in turn becomes susceptible to reasoning errors during the language-meaning verification process.
    • Large crowding zones in peripheral vision for briefly presented stimuli

      Tripathy, Srimant P.; Cavanagh, P.; Bedell, H.E. (2014-12)
      When a target is flanked by distractors, it becomes more difficult to identify. In the periphery, this crowding effect extends over a wide range of target-flanker separations, called the spatial extent of interaction (EoI). A recent study showed that the EoI dramatically increases in size for short presentation durations (Chung & Mansfield, 2009). Here we investigate this duration-EoI relation in greater detail and show that (a) it holds even when visibility of the unflanked target is equated for different durations, (b) the function saturates for durations shorter than 30 to 80 ms, and (c) the largest EoIs represent a critical spacing greater than 50% of eccentricity. We also investigated the effect of same or different polarity for targets and flankers across different presentation durations. We found that EoIs for target and flankers having opposite polarity (one white, the other black) show the same temporal pattern as for same polarity stimuli, but are smaller at all durations by 29% to 44%. The observed saturation of the EoI for shortduration stimuli suggests that crowding follows the locus of temporal integration. Overall, the results constrain theories that map crowding zones to fixed spatial extents or to lateral connections of fixed length in the cortex.
    • Laser capture microdissection on surgical tissues to identify aberrant gene expression in impaired wound healing in type 2 diabetes

      Williams, Rachel; Castellano-Pelicena, Irene; Al-Rikabi, Aaiad H.A.; Sikkink, Stephen K.; Baker, Richard; Riches-Suman, Kirsten; Thornton, M. Julie (2021-01-13)
      The global prevalence Type 2 diabetes mellitus (T2DM) is escalating at a rapid rate. Patients with T2DM suffer from a multitude of complications and one of these is impaired wound healing. This can lead to the development of non-healing sores or foot ulcers and ultimately to amputation. In healthy individuals, wound healing follows a controlled and overlapping sequence of events encompassing inflammation, proliferation, and remodelling. In T2DM, one or more of these steps becomes dysfunctional. Current models to study impaired wound healing in T2DM include in vitro scratch wound assays, skin equivalents, or animal models to examine molecular mechanisms underpinning wound healing and/or potential therapeutic options. However, these do not fully recapitulate the complex wound healing process in T2DM patients, and ex vivo human skin tests are problematic due to the ethics of taking punch biopsies from patients where it is known they will heal poorly. Here, a technique is described whereby expression profiles of the specific cells involved in the (dys)functional wound healing response in T2DM patients can be examined using surplus tissue discarded following amputation or elective cosmetic surgery. In this protocol samples of donated skin are collected, wounded, cultured ex vivo in the air liquid interface, fixed at different time points and sectioned. Specific cell types involved in wound healing (e.g., epidermal keratinocytes, dermal fibroblasts (papillary and reticular), the vasculature) are isolated using laser capture microdissection and differences in gene expression analyzed by sequencing or microarray, with genes of interest further validated by qPCR. This protocol can be used to identify inherent differences in gene expression between both poorly healing and intact skin, in patients with or without diabetes, using tissue ordinarily discarded following surgery. It will yield greater understanding of the molecular mechanisms contributing to T2DM chronic wounds and lower limb loss.
    • Laser scanning of skeletal pathological conditions

      Wilson, Andrew S.; Holland, Andrew D.; Sparrow, Thomas (2017-03)
    • Late Bronze Age exchange and interaction in the northern Circum-Alpine region: not only across the Alps

      Jennings, Benjamin R. (2017-10-23)
      Studies of Late Bronze Age exchange and communication networks in the northern Circum-Alpine region, and central Europe as a whole, have typically focused on routes across the Alps and the circulation of high-value manufactured goods from the Italian peninsula to central Europe. Some artefacts certainly support such a movement from north to south, such as amber from the north or Pfahlbauperlen from the Po Plain. However, such objects are far outweighed by the evidence for regional exchange routes in central Europe north of the Alps. Some of these routes extended as far as northern Germany and southern Scandinavia. Whether such exchange routes were direct or down-the-line is open to debate, but it is possible that specific objects known from Switzerland represent the personal possessions of migrant individuals. Over all, it is evident that Late Bronze Age lake-dwelling communities in Switzerland were significant bronze work manufacturing centres, exporting goods to varied communities and regions across central Europe, but with potentially limited exchange, transfer, and cross fertilization of styles and equipment between eastern and western Switzerland.
    • A Late Glacial family at Trollesgave. Denmark

      Donahue, Randolph E.; Fischer, Anders (2015-02)
      Microwear analysis is applied to reconstruct the function and social organisation at the Late Glacial site of Trollesgave, Denmark. As with Bromme Culture sites in general, the lithic assemblage consists of primarily three types of tools. There is a strong association between these types and their use: end scrapers for dry hide scraping; burins for working hard material, primarily bone; and tanged points primarily for projectile tips. Nearly all divergence from this pattern can be referred to as the activities of children, the products and workshops of which have previously been identified. Based on the combined information from microwear analysis, flint knapping and spatial distribution of artefacts, the assemblage is inferred as the traces of a single family hunting (and fishing) occupation.
    • A Later Bronze Age Shield from South Cadbury, Somerset, England

      Coles, J.M.; Leach, P.; Minnitt, S.C.; Tabor, R.; Wilson, Andrew S. (1999)
      A shield of beaten bronze from South Cadbury, Somerset, England is the first shield to be discovered by excavation on an archaeological site. The shield lay in a silt-filled Bronze Age ditch on a spur of land below Cadbury Castle. A stake was thrust through the shield. The paper considers the recovery and conservation of the shield, the technology of metal shields and the evidence for the ritual deposition of shields in the Later Bronze Age of western Europe.
    • LC-MS/MS Confirms That COX-1 Drives Vascular Prostacyclin whilst Gene Expression Pattern Reveals Non-Vascular Sites of COX-2 Expression.

      Kirkby, N.S.; Zaiss, A.K.; Urquhart, Paula; Jiao, J.; Austin, P.J.; Al-Yamani, M.; Lundberg, M.H.; MacKenzie, L.S.; Warner, T.D.; Nicolaou, Anna; et al. (2013-07-09)
      There are two schools of thought regarding the cyclooxygenase (COX) isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, we and others have found that COX-1, not COX-2, is responsible for vascular prostacyclin production. Our experiments have relied on immunoassays to detect the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to detect COX-2 protein. Whilst these are standard approaches, used by many laboratories, antibody-based techniques are inherently indirect and have been criticized as limiting the conclusions that can be drawn. To address this question, we measured production of prostanoids, including 6-keto-PGF1α, by isolated vessels and in the circulation in vivo using liquid chromatography tandem mass spectrometry and found values essentially identical to those obtained by immunoassay. In addition, we determined expression from the Cox2 gene using a knockin reporter mouse in which luciferase activity reflects Cox2 gene expression. Using this we confirm the aorta to be essentially devoid of Cox2 driven expression. In contrast, thymus, renal medulla, and regions of the brain and gut expressed substantial levels of luciferase activity, which correlated well with COX-2-dependent prostanoid production. These data are consistent with the conclusion that COX-1 drives vascular prostacyclin release and puts the sparse expression of Cox2 in the vasculature in the context of the rest of the body. In doing so, we have identified the thymus, gut, brain and other tissues as target organs for consideration in developing a new understanding of how COX-2 protects the cardiovascular system.
    • Le Castellan (Istres, Bouches-du-Rhône) : resultats de prospections géophysique

      Armit, Ian; Horsley, T.; Marty, F. (2016)
      Two seasons of geophysical prospection (magnetic, resistance and ground-penetrating radar) were conducted at the Iron Age oppidum of Le Castellan, Istres, Bouches-du-Rhône, in order to determine the utility of these techniques for sites in this region. The survey revealed numerous strong anomalies, of which many ran parallel or perpendicular to one another. These are the sorts of responses one might expect from the remains of buried stone wall foundations; this interpretation is supported by the presence, on the west side of the site, of exposed walls on the same alignment as certain of the geophysical anomalies. Overall, the evidence suggests a network of buried buildings and road-ways across the oppidum. One particularly substantial building was identified towards the centre of the site, through the presence of a strong resistance anomaly of distinctly rectilinear form. It appears to represent the remains of a buried stone building with three rooms. In conclusion, the results provide strong encouragement for the further application of geophysical survey in this region
    • Leading academic change: experiences of academic staff implementing team-based learning

      Nelson, M.; Tweddell, Simon (2017-09)
      Team-based learning (TBL) is a collaborative learning model that shifts classroom time from a teacher-centred to student-centred approach. TBL emphasises accountability to learning, teamwork, immediate feedback, peer feedback, and critical thinking. While many educators value the increased student engagement that results from TBL, the transition from traditional teaching methods to TBL poses challenges. Using a qualitative approach, this study aimed to explore the experiences of 26 academic staff in the United Kingdom who implemented TBL in the higher education setting. Thematic analysis of interview text generated eight themes related to preparing academics to use TBL, challenges related to TBL, and engagement of students with the curriculum. Derived from these themes, a set of recommendations for supporting academic staff who transition to TBL was developed.
    • 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.
    • A learning development-faculty collaborative exploration of postgraduate research student mental health in a UK university

      Delderfield, Russell; Ndoma-Egba, Mathias; Riches-Suman, Kirsten; Boyne, J. (2020-10)
      Mental ill-health is an escalating problem in higher education. Not only does this impact students’ ability to learn, it can lead to poor completion, with learners opting to withdraw from studies, even if attainment has been satisfactory. The aim of this study was to gain insight about perceptions of poor mental health from postgraduate research students in a diverse UK university and canvas opinion regarding how the University could improve this. A short, pragmatic survey with basic quantitative and qualitative responses was distributed. This was analysed by a team comprising the learning developer responsible for postgraduate researcher learning development, academics and a doctoral student. The study found that poor mental health was evident, with over three quarters of respondents reporting some experience of mental ill-health. We identified five areas in need of attention: University Systems, Supervisor Training, Well-being Monitoring, Building Networks, and Finance. Sources of University-based stress were finance, administrative support, and an environment where a perception that poor mental health was an expectation rather than a problem was experienced. Students preferred to access support outside the academic environment. This is the first study of its kind at a diverse, plate-glass UK university, to consider research student mental ill-health, with a staff-student team working with data, and the learning developer spear-heading changes across postgraduate research. These findings have already influenced university strategy, staff training, and induction practices. The synthesis of the five areas could be used to visualise where further work is needed to improve mental health in these learners.
    • 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)