• Keeping the dead close: grief and bereavement in the treatment of skulls from the Neolithic Middle East

      Croucher, Karina T. (2018)
      Theories of Continuing Bonds, and more recently, the Dual Process of Grieving, have provided new ways of understanding the bereavement process, and have influenced current practice for counsellors, end-oflife care practitioners and other professionals. This paper uses these theories in a new way, exploring their relevance to archaeological interpretation, with particular reference to the phenomenon of the plastering of skulls of the deceased in the Neolithic of Southwest Asia (the Middle East/Near East), suggesting that traditional archaeological interpretations, which focus on concepts of status and social organisation, may be missing a more basic reaction to grief and a desire to keep the dead close for longer.
    • A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide–induced proarrhythmic early afterdepolarizations

      Al-Owais, M.M.; Hettiarachchi, N.T.; Kirton, H.M.; Hardy, Matthew E.; Boyle, J.P.; Scragg, J.L.; Steele, D.S.; Peers, C. (2017-11-01)
      Exposure to CO causes early afterdepolarization arrhythmias. Previous studies in rats have indicated that arrhythmias arose as a result of augmentation of the late Na+ current. The purpose of the present study was to examine the basis for CO-induced arrhythmias in guinea pig myocytes in which action potentials (APs) more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes as well as from human embryonic kidney 293 (HEK293) cells that express wild-type or a C723S mutant form of ether-a-go-go–related gene (ERG; Kv11.1). We also monitored the formation of peroxynitrite (ONOO−) in HEK293 cells fluorimetrically. CO—applied as the CO-releasing molecule, CORM-2—prolonged the APs and induced early afterdepolarizations in guinea pig myocytes. In HEK293 cells, CO inhibited wild-type, but not C723S mutant, Kv11.1 K+ currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors, or inhibition of NO formation. CO also raised ONOO− levels, an effect that was reversed by the ONOO− scavenger, FeTPPS [5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato-iron(III)], which also prevented the CO inhibition of Kv11.1 currents and abolished the effects of CO on Kv11.1 tail currents and APs in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes via the ONOO−-mediated inhibition of Kv11.1 K+ channels.
    • Kinase regulation of HOX transcription factors

      Primon, Monika; Hunter, K.D.; Pandha, H.S.; Morgan, Richard (2019-04)
      The HOX genes are a group of homeodomain-containing transcription factors that play important regulatory roles in early development, including the establishment of cell and tissue identity. HOX expression is generally reduced in adult cells but is frequently re-established as an early event in tumour formation and supports an oncogenic phenotype. HOX transcription factors are also involved in cell cycle regulation and DNA repair, along with normal adult physiological process including stem cell renewal. There have been extensive studies on the mechanism by which HOX proteins regulate transcription, with particular emphasis on their interaction with cofactors such as Pre-B-cell Leukaemia Homeobox (PBX) and Myeloid Ecotropic Viral Integration Site 1 (MEIS). However, significantly less is known of how the activity of HOX proteins is regulated. There is growing evidence that phosphorylation may play an important role in this context, and in this review, we draw together a number of important studies published over the last 20 years, and discuss the relevance of phosphorylation in the regulation and function of HOX proteins in development, evolution, cell cycle regulation, and cancer.
    • Klüver-Bucy Syndrome following traumatic brain injury: a systematic synthesis and review of pharmacological treatment from cases in adolescents and adults

      Clay, F.J.; Kuriakose, A.; Lesche, D.; Hicks, A.J.; Zaman, Hadar; Azizi, E.; Ponsford, J.L.; Jayaram, M.; Hopwood, M. (2018)
      Klüver-Bucy syndrome (KBS) is a rare clinical presentation following traumatic brain injury (TBI). Symptoms include visual agnosia, placidity, hyperorality, sexual hyperactivity, changes in dietary behavior, and hypermetamorphosis. The purpose of this article was to identify and synthesize the available evidence from case reports and case series on the treatment profile of KBS among adolescents and adults after TBI. Four bibliographic databases (MEDLINE OVID, EMBASE, PsycINFO, and SCOPUS) were searched for relevant literature. No date or language restrictions were applied. All case reports containing original data on KBS following TBI among adolescents and adults were included. Articles were evaluated, and data were extracted according to predefined criteria. The literature search identified 24 case reports of KBS post-TBI published between 1968 and 2017. Most case subjects were male (70.1%), and the mean age at injury was 25.1 years (range, 13–67 years). Injury to one or both temporal lobes occurred in most cases. Inappropriate sexual hyperactivity was the most common KBS symptom, followed by a change in dietary behavior and hyperorality. Visual agnosia was the least reported. In 50% of cases, the patient fully recovered from KBS. One-half of all participants described pharmacological management; the most common medication prescribed was carbamazepine. Overall, there was a lack of data available on pharmacotherapy initiation and duration. The complex presentation of KBS presents challenges in terms of treatment options. Although overall individuals who were prescribed carbamazepine had positive outcomes, given the reliance on case reports, it is difficult to make a definitive recommendation to guide clinical practice.
    • A knight's tale: a rare case of inter-personal violence from medieval Norton Priory

      Curtis-Summers, Shirley; Boylston, Anthea; Ogden, Alan R. (2016-05)
      The opportunity to assess human skeletal remains from Norton Priory, near Runcorn (Cheshire), led to the discovery of peri-mortem blade trauma on an adult male skeleton. The burial evidence suggests that this individual was a wealthy knight and lay benefactor of the priory in the thirteenth century and skeletal evidence has revealed that he was the victim of inter-personal violence. Additionally, many skeletal elements were affected by advanced Paget’s disease, which may have resulted in a certain level of vulnerability due to restricted movement of his arms as a result of Pagetic thickening of the bones. This is the only evidence found of weaponrelated trauma on the Norton Priory skeletal assemblage, making it a rare case and contributing to our understanding of inter-personal violence associated with an ecclesiastical establishment in medieval Britain.
    • 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 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. (2018)
      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.
    • 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.