1,252 research outputs found

    Multicenter evaluation of geometric accuracy of MRI protocols used in experimental stroke

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    It has recently been suggested that multicenter preclinical stroke studies should be carried out to improve translation from bench to bedside, but the accuracy of magnetic resonance imaging (MRI) scanners routinely used in experimental stroke has not yet been evaluated. We aimed to assess and compare geometric accuracy of preclinical scanners and examine the longitudinal stability of one scanner using a simple quality assurance (QA) protocol. Six 7 Tesla animal scanners across six different preclinical imaging centers throughout Europe were used to scan a small structural phantom and estimate linear scaling errors in all orthogonal directions and volumetric errors. Between-scanner imaging consisted of a standard sequence and each center’s preferred sequence for the assessment of infarct size in rat models of stroke. The standard sequence was also used to evaluate the drift in accuracy of the worst performing scanner over a period of six months following basic gradient calibration. Scaling and volumetric errors using the standard sequence were less variable than corresponding errors using different stroke sequences. The errors for one scanner, estimated using the standard sequence, were very high (above 4% scaling errors for each orthogonal direction, 18.73% volumetric error). Calibration of the gradient coils in this system reduced scaling errors to within ±1.0%; these remained stable during the subsequent 6-month assessment. In conclusion, despite decades of use in experimental studies, preclinical MRI still suffers from poor and variable geometric accuracy, influenced by the use of miscalibrated systems and various types of sequences for the same purpose. For effective pooling of data in multicenter studies, centers should adopt standardized procedures for system QA and in vivo imaging

    Risk of Bias in Reports of In Vivo Research: A Focus for Improvement

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    The reliability of experimental findings depends on the rigour of experimental design. Here we show limited reporting of measures to reduce the risk of bias in a random sample of life sciences publications, significantly lower reporting of randomisation in work published in journals of high impact, and very limited reporting of measures to reduce the risk of bias in publications from leading United Kingdom institutions. Ascertainment of differences between institutions might serve both as a measure of research quality and as a tool for institutional efforts to improve research quality

    A randomised controlled trial of an Intervention to Improve Compliance with the ARRIVE guidelines (IICARus)

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    Background: The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines. Methods: In a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March-June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems. Results: We randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X 2 = 34.0, df = 1, p = 2.1 × 10-7) in the control and intervention groups, respectively. Conclusions: These results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting

    ERP correlates of forgetting: an investigation of resource allocation as a potential neural mechanism behind retrieval-induced forgetting

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    The present study was aimed at investigating a potential mechanism behind retrieval-induced forgetting that we have termed resource allocation. Three experiments were designed around the notion that increasing the number memories associated with one concept may reduce retrieval-induced forgetting by spreading out the limited resources available for that concept. In two experiments, we expanded the standard retrieval-induced forgetting (RIF) paradigm by increasing the number of items in each category and varying the amount of Rp+ and Rp- items. In one of these experiments, we recorded event-related potentials (ERPs) to examine the electrophysiological correlates of retrieval-induced forgetting. We then compared these findings to a standard version of the RIF paradigm as a control experiment. All three experiments produced significant facilitation effects, but failed to produce retrieval-induced forgetting. The absence of RIF in the present study, however, when combined with the imaging data allows us to discern the ERP correlates of selective retrieval from those of retrieval-induced forgetting. In the discussion, we present our case against conclusions drawn in other studies about the ERP correlates of RIF, and suggest that the characteristic frontoparietal components often found in RIF studies reflect the neural correlates of selective retrieval rather than inhibition

    Introduction to the EQIPD quality system

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    Fundings: Innovative Medicines Initiative (777364) to Malcolm R MacLeod. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.Peer reviewe

    AAC Malcolm hulless barley

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    AAC Malcolm is a hulless, six-row spring barley (Hordeum vulgare L.) cultivar adapted to the growing conditions of eastern Canada. It was evaluated in the Ontario Barley Orthogonal Test (2018-2020) before being registered in Canada in 2023. AAC Malcolm is high in yield and good lodging resistance. AAC Malcolm is recommended for commercial production in eastern Canada.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author

    What do we really know about cognitive inhibition? Task demands and inhibitory effects across a range of memory and behavioural tasks

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    The authors (SN, principal investigator and MDM as co-investigator) received funding from the British Academy for this research (http://www.britac.ac.uk/). The grant number was SG111104.Our study explores inhibitory control across a range of widely recognised memory and behavioural tasks. Eighty-seven never-depressed participants completed a series of tasks designed to measure inhibitory control in memory and behaviour. Specifically, a variant of the selective retrieval-practice and the Think/No-Think tasks were employed as measures of memory inhibition. The Stroop-Colour Naming and the Go/No-Go tasks were used as measures of behavioural inhibition. Participants completed all 4 tasks. Task presentation order was counterbalanced across 3 separate testing sessions for each participant. Standard inhibitory forgetting effects emerged on both memory tasks but the extent of forgetting across these tasks was not correlated. Furthermore, there was no relationship between memory inhibition tasks and either of the main behavioural inhibition measures. At a time when cognitive inhibition continues to gain acceptance as an explanatory mechanism, our study raises fundamental questions about what we actually know about inhibition and how it is affected by the processing demands of particular inhibitory tasks.Peer reviewe

    Development of a psychological intervention for post-stroke fatigue

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    Background Post-stroke fatigue (PSF) is a common and distressing problem after stroke. It impedes patients’ participation in daily activities and is associated with higher risks of institutionalisation and death following stroke. Despite its high prevalence and detrimental consequences, little research has been conducted to develop effective treatments for PSF. Psychological interventions are effective in treating fatigue in other conditions such as cancer and chronic fatigue syndrome. This thesis described the development of a psychological intervention for PSF. Methods This thesis was based on the theoretical, modelling and part of the piloting phases of the Medical Research Council (MRC) framework for designing and evaluating complex interventions. This intervention was developed in collaboration with a multidisciplinary group of stroke clinicians, clinical psychologists, a psychotherapist, and stroke survivors. Both qualitative and quantitative methods were used. Systematic reviews were conducted to explore the natural history of PSF and to identify potential targets for a psychological intervention for PSF. The format of the intervention was adapted from existing psychological interventions for cancer-related fatigue and chronic fatigue syndrome. The intervention was delivered by a clinical psychologist (i.e. the therapist) to 12 patients with PSF (i.e. the participants) to test its acceptability and feasibility in the local health system. After the feasibility study, the intervention was refined according to the feedback from the participants and the therapist. A Cochrane review of interventions for PSF was updated to identify any new evidence that could inform future studies. Results Systematic reviews suggested that PSF often occurred early after stroke and persisted over time (which justified the need for interventions for PSF) and that PSF was associated with distressed mood, lower self-efficacy, reduced physical activity and sleeping problems (which were potential targets for the treatment of PSF). Based on interventions that have been used to treat fatigue in other conditions, these psychological and behavioural factors could be addressed by psychological interventions that challenge patients’ thoughts and behaviours (i.e. the cognitive behavioural therapy, CBT). Thus a manualised CBT was developed for PSF. This CBT was delivered to each participant individually, through six face-to-face treatment sessions over a period of 12 weeks, followed by a telephone-delivered review session one month later. Both the participants and the therapist gave favourable opinions on the acceptability of the intervention. The recruitment and follow-up procedures were feasible in the local health system. Following the feedback from participants and therapist, the intervention manual was refined for future use, where the last two treatment sessions will be combined to a single session and the review session will be delivered in person by the therapist. There were statistically significant improvements in fatigue, mood, mobility, and participation in social activity from baseline to three months after the end of treatment. The updated Cochrane review concluded that there was insufficient evidence to recommend any specific intervention for PSF; psychological interventions are one type of interventions worth being investigated in future trials. Conclusions PSF is associated with distressed mood, lower self-efficacy, reduced physical activity and sleeping problems, which are potential targets for the treatment of PSF. Although there was insufficient evidence to recommend any intervention for the treatment of PSF, psychological interventions are one type of promising interventions worth future investigation. The promising results from this uncontrolled feasibility study support the need for a subsequent exploratory randomised controlled trial (RCT) of this brief psychological intervention

    Systematic review and meta-analysis of animal models of acute ischaemic stroke

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    Ischaemic stroke is responsible for substantial death and disability and creates a huge financial burden for healthcare budgets worldwide. At present there are few effective treatments for acute stroke and these are urgently required. Increased understanding of the ischaemic cascade has generated interest in neuroprotection for focal cerebral ischaemia. However, treatment effects observed in of over 500 interventions in animal models have yet to be translated to the clinic. Systematic review and meta-analysis allows unbiased identification of all relevant data for a given intervention, gives a clearer view of its true efficacy and the limitations to its therapeutic potential. Understanding the reasons for this bench-to-bedside failure and providing quantitative explanations may help to address these discrepancies. Random effects weighted mean difference meta-analysis of six interventions (tirilazad, tPA, NXY-059, Hypothermia, Piracetam and IL1-RA) reported study quality to be consistently low. In some instances, potential sources of bias were associated with overestimations of efficacy. Likewise, clinical trials have tested interventions in conditions where efficacy was not observed in animals. Cumulative meta-analysis suggests that for tPA the estimate of efficacy is stable after the inclusion of data from 1500 animals; hypothermia and FK506 are the only other interventions to have been tested in at least 1500 animals. Meta-regression suggests biological rather methodical factors are better predictors of outcome; a major limitation of these data is the impact of publication bias, and this work suggests effect sizes from met-analyses are inflated by about 31% because 16% of studies remain unpublished. The systematic review and meta-analysis of hypothermia was used to plan experiments investigating the possible impact of pethidine, a drug used to prevent shivering. This in vivo experiment, in which potential sources of bias were minimised, suggests that pethidine does not influence the observed efficacy of hypothermia in an animal model of ischaemic stroke. This thesis reports that animal studies of ischaemic stroke are often not conducted with sufficient rigour. Both minimising potential sources of bias in individual experiments and using meta-analysis to summarise data from a number of experiments may be helpful in improving the translation of neuroprotective efficacy in ischaemic stroke

    The Malcolm Baldridge Quality Award and engineering technology education

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    In 1988, the Department of Commerce with assistance from the American Society for Quality Control presented the first Malcolm Baldrige National Quality Award. This award is modeled after the Deming Prize given annually in Japan since 1951. The award is presented to organizations that are totally committed to a quality philosophy in either service or manufacturing. Organizations apply for award consideration and must do a comprehensive self-appraisal followed by an on-site audit by volunteer quality professionals. The author considers how engineering technology programs would withstand a Malcolm Baldrige Quality Award appraisal. He discusses the Malcolm Baldrige criteria and how they can be applied to improve all engineering technology programs
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