601 research outputs found

    Enlightenment museums: universal or merely global?

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    This article tests the case set out by the 2002 Declaration, signed by many of the great museums of the world, and elaborated by Neil MacGregor, the Director of the British Museum (BM), that these are universal institutions whose displays enable visitors ‘to see the world as one’ and hence promote a more tolerant society. I argue that while a universal museum could be invaluable in a world full of conflict and misunderstanding, the credibility of the idea is undermined by its being deployed chiefly as a defense against repatriation claims. MacGregor’s accounts of the Benin Bronzes, the Elgin/Parthenon Marbles and the Rosetta Stone are examined as to whether they provide historical, ethical or epistemological support for the idea of the universal museum. I review the current display practices of ‘universal museums’ and argue that they are as likely to confirm prejudice as to promote tolerance. I conclude with an alternative view of what a universal museum might be – one which is open about the conflicted histories of some objects, which acknowledges historical context as well as aesthetics, explores violent as well as peaceful cultural encounters and reveals the Imperial as well as the Enlightenment history of collections

    Evidence for public health on novel psychoactive substance use: a mixed-methods study

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    Background: Novel psychoactive substances (NPSs) contribute to the public health impact of substance misuse. This report provides research evidence addressing 11 research questions related to NPSs, covering types, patterns and settings of use; supply sources; and implications for policy and practice. Methods: The study used a conceptually linked three-phase mixed-methods design with a shared conceptual framework based on multiple-context risk and protective factors. Phase 1 was a quantitative phase involving secondary data analysis of the longitudinal Belfast Youth Development Study (BYDS), a latent class analysis using the 2039 BYDS participants. Phase 2 was an extensive qualitative analysis via narrative interviews with participants, sampled from BYDS, drug/alcohol services and prisons, to explore NPS use trajectories. Phase 3 was the final quantitative phase; generalisability of the shared risk factor part of the model was tested using the manual three-step approach to examine risk factors associated with latent class membership. The quantitative and qualitative analyses were integrated, thus allowing emerging findings to be further explored. Results: The data suggest that NPSs have a place within a range of polydrug use trajectories. Models showed no distinctive NPS class, with no clear evidence of differential risks for NPS use compared with the use of other substances. From the qualitative analysis, a taxonomy of groups was derived that explored how and where NPSs featured in a range of trajectories. This taxonomy was used to structure the analysis of factors linked to use within a risk and protective framework. Drivers for use were considered alongside knowledge, perceptions and experience of harms. Suggestions about how interventions could best respond to the various patterns of use – with special consideration of synthetic cannabinoids (SCs), including how they relate to the use of heroin and the potential for NPSs to operate as a ‘snare’ to more problem use – were also presented. Limitations: The study was conducted during 2016/17; generalisability beyond this sample and time point is limited. The level of missing data for some of the BYDS analysis was a limitation, as was the fact that the BYDS data were collected in 2011, so in a different context from the data collected during the narrative interviews. The Psychoactive Substances Act 2016 (Great Britain. Psychoactive Substances Act 2016. London: The Stationery Office; 2016) came into force during qualitative fieldwork and, although not particularly influential in this study, may be influential in future work. It is acknowledged that many of the data related to SCs and mephedrone. Although drug use was measured by self-report, the strength of rapport within interviews, reflective diaries and methodological acceptability checks helped to mitigate self-report bias. Conclusions: NPSs continue to present significant challenges for legislation and monitoring, researching and developing interventions. Understanding of usage patterns remains poor, with most information based on populations and settings where problems have already occurred. This research contributes to the evidence base by providing much needed further empirical data on the lived experiences of NPS users across a range of settings. In the light of these data, implications for policy and practice are discussed. Future work: Future research must generate improved epidemiological data on the extent, patterns and motivations for use longitudinally. The uniqueness of the information concerning SC use points to a specific set of findings not evidenced in other literature (e.g. intensity of SC withdrawal). Future research should focus on the symbiotic link between SC and heroin use

    FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels

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    AbstractThis study compared the relative levels of ryanodine receptor (RyR) isoforms, inositol 1,4,5-trisphosphate receptor (IP3R) isoforms, and calcineurin, plus their association with FKBP12 in brain, skeletal and cardiac tissue. FKBP12 demonstrated a very tight, high affinity association with skeletal muscle microsomes, which was displaced by FK506. In contrast, FKBP12 was not tightly associated with brain or cardiac microsomes and did not require FK506 for removal from these organelles. Furthermore, of the proteins solubilised from skeletal muscle, cardiac muscle and brain microsomes, only skeletal muscle RyR1 bound to an FKBP12–glutathione-S-transferase fusion protein, in a high affinity FK506 displaceable manner. These results suggest that RyR1 has distinctive FKBP12 binding properties when compared to RyR2, RyR3, all IP3R isoforms and calcineurin

    An Approach to Catheter Ablation of Cavotricuspid Isthmus Dependent Atrial Flutter

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    Much of our understanding of the mechanisms of macro re-entrant atrial tachycardia comes from study of cavotricuspid isthmus (CTI) dependent atrial flutter. In the majority of cases, the diagnosis can be made from simple analysis of the surface ECG. Endocardial mapping during tachycardia allows confirmation of the macro re-entrant circuit within the right atrium while, at the same time, permitting curative catheter ablation targeting the critical isthmus of tissue located between the tricuspid annulus and the inferior vena cava. The procedure is short, safe and by demonstration of an electrophysiological endpoint - bidirectional conduction block across the CTI - is associated with an excellent outcome following ablation. It is now fair to say that catheter ablation should be considered as a first line therapy for patients with documented CTI-dependent atrial flutter

    Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10

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    TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR adaptor-induced activation of NF-kB and the IFN regulatory factors have been intensively studied, there is a dearth of information on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4 ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase 2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFRassociated factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38 MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory gen

    Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10

    Get PDF
    TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR adaptor-induced activation of NF-kB and the IFN regulatory factors have been intensively studied, there is a dearth of information on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4 ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase 2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFRassociated factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38 MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory gen

    The relationship between manual coordination and mental health

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    Motor coordination impairments frequently co-occur with other developmental disorders and mental health problems in clinically referred populations. But does this reflect a broader dimensional relationship within the general population? A clearer understanding of this relationship might inform improvements in mental health service provision. However, ascertainment and referral bias means that there is limited value in conducting further research with clinically referred samples. We, therefore, conducted a cross-sectional population-based study investigating children’s manual coordination using an objective computerised test. These measures were related to teacher-completed responses on a behavioural screening questionnaire [the Strength and Difficulties Questionnaire (SDQ)]. We sampled 298 children (4–11 years old; 136 males) recruited from the general population. Hierarchical (logistic and linear) regression modelling indicated significant categorical and continuous relationships between manual coordination and overall SDQ score (a dimensional measure of psychopathology). Even after controlling for gender and age, manual coordination explained 15 % of the variance in total SDQ score. This dropped to 9 % after exclusion of participants whose SDQ responses indicated potential mental health problems. These results: (1) indicate that there is a clear relationship between children’s motor and mental health development in community-based samples; (2) demonstrate the relationship’s dimensional nature; and (3) have implications for service provision.</p

    Impact of catheter ablation versus medical therapy on cognitive function in atrial fibrillation: a systematic review

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    PURPOSE: Atrial fibrillation is associated with an increased risk of cognitive impairment. It is unclear whether the restoration of sinus rhythm with catheter ablation may modify this risk. We conducted a systematic review of studies comparing cognitive outcomes following catheter ablation with medical therapy (rate and/or rhythm control) in atrial fibrillation. METHODS: Searches were performed on the following databases from their inception to 17 October 2021: PubMed, OVID Medline, Embase and Cochrane Library. The inclusion criteria comprised studies comparing catheter ablation against medical therapy (rate and/or rhythm control in conjunction with anticoagulation where appropriate) which included cognitive assessment and/or a diagnosis of dementia as an outcome. RESULTS: A total of 599 records were screened. Ten studies including 15,886 patients treated with catheter ablation and 42,684 patients treated with medical therapy were included. Studies which compared the impact of catheter ablation versus medical therapy on quantitative assessments of cognitive function yielded conflicting results. In studies, examining new onset dementia during follow-up, catheter ablation was associated with a lower risk of subsequent dementia diagnosis compared to medical therapy (hazard ratio: 0.60 (95% confidence interval 0.42–0.88, p < 0.05)). CONCLUSION: The accumulating evidence linking atrial fibrillation with cognitive impairment warrants the design of atrial fibrillation treatment strategies aimed at minimising cognitive decline. However, the impact of catheter ablation and atrial fibrillation medical therapy on cognitive decline is currently uncertain. Future studies investigating atrial fibrillation treatment strategies should include cognitive outcomes as important clinical endpoints. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10840-022-01196-y
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