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BACKGROUND: Research impact is an emerging measure of research achievement alongside traditional academic outputs such as publications. We present the results of applying the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence (CRE) in Stroke Rehabilitation and Brain Recovery (CRE-Stroke, 2014-2019) and report on the feasibility and lessons from the application of FAIT to a CRE rather than a discrete research project. METHODS: Data were gathered via online surveys, in-depth interviews, document analysis and review of relevant websites/databases to report on the three major FAIT methods: the modified Payback Framework, an assessment of costs against monetized consequences, and a narrative account of the impact generated from CRE-Stroke activities. FAIT was applied during the last 4 years of CRE-Stroke operation. RESULTS: With an economic investment of AU$ 3.9 million over 5 years, CRE-Stroke delivered a return on investment that included AU$ 18.8 million in leveraged grants, fellowships and consultancies. Collectively, CRE-Stroke members produced 354 publications that were accessed 470,000 times and cited over 7220 times. CRE-Stroke supported 26 PhDs, 39 postdocs and seven novice clinician researchers. There were 59 capacity-building events benefiting 744 individuals including policy-makers and consumers. CRE-Stroke created research infrastructure (including a research register of stroke survivors and a brain biobank), and its global leadership produced international consensus recommendations to influence the stroke research landscape worldwide. Members contributed to the Australian Living Stroke Guidelines: four researchers' outputs were directly referenced. Based only on the consequences that could be monetized, CRE-Stroke returned AU$ 4.82 for every dollar invested in the CRE. CONCLUSION: This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstr

INTRODUCTION: The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. METHODS AND ANALYSIS: This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and

INTRODUCTION: Stroke reperfusion therapies, comprising intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), are best practice treatments for eligible acute ischemic stroke patients. In Australia, EVT is provided at few, mainly metropolitan, comprehensive stroke centres (CSC). There are significant challenges for Australia's rural and remote populations in accessing EVT, but improved access can be facilitated by a 'drip and ship' approach. TACTICS (Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship) aims to test whether a multicomponent, multidisciplinary implementation intervention can increase the proportion of stroke patients receiving EVT. METHODS AND ANALYSIS: This is a non-randomised controlled, stepped wedge trial involving six clusters across three Australian states. Each cluster comprises one CSC hub and a minimum of three primary stroke centre (PSC) spokes. Hospitals will work in a hub and spoke model of care with access to a multislice CT scanner and CT perfusion image processing software (MIStar, Apollo Medical Imaging). The intervention, underpinned by behavioural theory and technical assistance, will be allocated sequentially, and clusters will move from the preintervention (control) period to the postintervention period. PRIMARY OUTCOME: Proportion of all stroke patients receiving EVT, accounting for clustering. SECONDARY OUTCOMES: Proportion of patients receiving IVT at PSCs, proportion of treated patients (IVT and/or EVT) with good (modified Rankin Scale (mRS) score 0-2) or poor (mRS score 5-6) functional outcomes and European Quality of Life Scale scores 3 months postintervention, proportion of EVT-treated patients with symptomatic haemorrhage, and proportion of reperfusion therapy-treated patients with good versus poor outcome who presented with large vessel occlusion at spokes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Hunter New England Human Research Ethics Committee (18/09

Modern work environments have extensive interactions with technology and greater cognitive complexity of the tasks, which results in human operators experiencing increased mental workload. Air traffic control operators routinely work in such complex environments, and we designed tracking and collision prediction tasks to emulate their elementary tasks. The physiological response to the workload variations in these tasks was elucidated to untangle the impact of workload variations experienced by operators. Electroencephalogram (EEG), eye activity, and heart rate variability (HRV) data were recorded from 24 participants performing tracking and collision prediction tasks with three levels of difficulty. Our findings indicate that variations in task load in both these tasks are sensitively reflected in EEG, eye activity and HRV data. Multiple regression results also show that operators' performance in both tasks can be predicted using the corresponding EEG, eye activity and HRV data. The results also demonstrate that the brain dynamics during each of these tasks can be estimated from the corresponding eye activity, HRV and performance data. Furthermore, the markedly distinct neurometrics of workload variations in the tracking and collision prediction tasks indicate that neurometrics can provide insights on the type of mental workload. These findings have applicability to the design of future mental workload adaptive systems that integrate neurometrics in deciding not just "when" but also "what" to adapt. Our study provides compelling evidence in the viability of developing intelligent closed-loop mental workload adaptive systems that ensure efficiency and safety in complex work environments.

BackgroundCardiorespiratory fitness (CRF) is an important marker of current and future health status. The primary aim of our study was to evaluate the impact of a time-efficient school-based intervention on older adolescents’ CRF.MethodsTwo-arm cluster randomised controlled trial conducted in two cohorts (February 2018 to February 2019 and February 2019 to February 2020) in New South Wales, Australia. Participants (N=670, 44.6% women, 16.0±0.43 years) from 20 secondary schools: 10 schools (337 participants) were randomised to the Burn 2 Learn (B2L) intervention and 10 schools (333 participants) to the control. Teachers in schools allocated to the B2L intervention were provided with training, resources, and support to facilitate the delivery of high-intensity interval training (HIIT) activity breaks during curriculum time. Teachers and students in the control group continued their usual practice. The primary outcome was CRF (20 m multi-stage fitness test). Secondary outcomes were muscular fitness, physical activity, hair cortisol concentrations, mental health and cognitive function. Outcomes were assessed at baseline, 6 months (primary end-point) and 12 months. Effects were estimated using mixed models accounting for clustering.ResultsWe observed a group-by-time effect for CRF (difference=4.1 laps, 95% CI 1.8 to 6.4) at the primary end-point (6 months), but not at 12 months. At 6 months, group-by-time effects were found for muscular fitness, steps during school hours and cortisol.ConclusionsImplementing HIIT during curricular time improved adolescents’ CRF and several secondary outcomes. Our findings suggest B2L is unlikely to be an effective approach unless teachers embed sessions within the school day.

Delays in acute stroke treatment contribute to severe and negative impacts for patients and significant healthcare costs. Variability in clinical care is a contributor to delayed treatment, particularly in rural, regional and remote (RRR) areas. Targeted approaches to improve stroke workflow processes improve outcomes, but numerous challenges exist particularly in RRR settings. Virtual reality (VR) applications can provide immersive and engaging training and overcome some existing training barriers. We recently initiated the TACTICS trial, which is assessing a "package intervention" to support advanced CT imaging and streamlined stroke workflow training. As part of the educational component of the intervention we developed TACTICS VR, a novel VR-based training application to upskill healthcare professionals in optimal stroke workflow processes. In the current manuscript, we describe development of the TACTICS VR platform which includes the VR-based training application, a user-facing website and an automated back-end data analytics portal. TACTICS VR was developed via an extensive and structured scoping and consultation process, to ensure content was evidence-based, represented best-practice and is tailored for the target audience. Further, we report on pilot implementation in 7 Australian hospitals to assess the feasibility of workplace-based VR training. A total of 104 healthcare professionals completed TACTICS VR training. Users indicated a high level of usability, acceptability and utility of TACTICS VR, including aspects of hardware, software design, educational content, training feedback and implementation strategy. Further, users self-reported increased confidence in their ability to make improvements in stroke management after TACTICS VR training (post-training mean ± SD = 4.1 ± 0.6; pre-training = 3.6 ± 0.9; 1 = strongly disagree, 5 = strongly agree). Very few technical issues were identified, supporting the feasibility of this training approach. Thus, we p

Autism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder characterised by deficits in social communication, and restricted and/or repetitive behaviours. While the precise pathophysiologies are unclear, increasing evidence supports a role for dysregulated neuroinflammation in the brain with potential effects on synapse function. Here, we studied characteristics of microglia and astrocytes in the Neuroligin-3 (NL3R451C) mouse model of autism since these cell types are involved in regulating both immune and synapse function. We observed increased microglial density in the dentate gyrus (DG) of NL3R451C mice without morphological differences. In contrast, WT and NL3R451C mice had similar astrocyte density but astrocyte branch length, the number of branch points, as well as cell radius and area were reduced in the DG of NL3R451C mice. Because retraction of astrocytic processes has been linked to altered synaptic transmission and dendrite formation, we assessed for regional changes in pre- and postsynaptic protein expression in the cortex, striatum and cerebellum in NL3R451C mice. NL3R451C mice showed increased striatal postsynaptic density 95 (PSD-95) protein levels and decreased cortical expression of synaptosomal-associated protein 25 (SNAP-25). These changes could contribute to dysregulated neurotransmission and cognition deficits previously reported in these mice.

BACKGROUND: There is growing recognition that the wider benefits of research (economic, social and health impacts) should be assessed and valued alongside traditional research performance metrics such as peer-reviewed papers. Translation of findings into policy and practice needs to accelerate and pathways to impact need to be better understood. This research protocol outlines a mixed methods study to apply the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery (CRE-Stroke). FAIT is purpose-designed to encourage research translation and assess research impact but lacks validation. METHODS/DESIGN: Phase 1 involves application of the FAIT-modified programme logic model to each CRE-Stroke research stream including identifying process, output and impact metrics, as well as end users of the research. A scoping review will inform potential impacts anticipated from CRE-Stroke. In Phase 2, audit and feedback on achievements against plans will track and encourage research translation. Logic models will be updated to account for changes in the research pathways over time. In Phase 3, three proven methods for measuring research impact - Payback, economic assessment and narratives - will be applied to each research stream and the data triangulated and reported in Phase 4. The feasibility of applying FAIT will also be assessed as part of Phase 3. DISCUSSION: Use of prospective, comprehensive research impact frameworks for large interdisciplinary programmes of research is rare. FAIT's application to CRE-Stroke will provide opportunity for the impact of CRE-Stroke to be assessed and a range of impacts beyond standard academic achievements to be reliably reported. The feasibility of FAIT's application will also be assessed and, if necessary, refined. The usefulness of FAIT for encouraging research translation will also be described and may prove useful for other programmes lookin

BACKGROUND: Stroke survivors sit for long periods each day. Uninterrupted sitting is associated with increased risk of cardiovascular disease. Breaking up uninterrupted sitting with frequent, short bouts of light-intensity physical activity has an immediate positive effect on blood pressure and plasma clotting factors in healthy, overweight, and type 2 diabetic populations. AIM: We examined the effect of frequent, short bouts of light-intensity physical activity on blood pressure and plasma fibrinogen in stroke survivors. METHODS: Prespecified secondary analyses from a three-armed randomized, within-participant, crossover trial. Participants were 19 stroke survivors (nine female, aged 68 years old, 90% able to walk independently). The experimental conditions were sitting for 8 h uninterrupted, sitting with 3 min bouts of light-intensity exercise while standing every 30 min, or sitting with 3 min of walking every 30 min. Blood pressure was measured every 30 min over 8 h and plasma fibrinogen at the beginning, middle, and end of each day. Intention-to-treat analyses were performed using linear mixed models including fixed effects for condition, period, and order, and a random intercept for participant to account for repeated measures and missing data. RESULTS: Sitting with 3 min bouts of light-intensity exercise while standing every 30 min decreased systolic blood pressure by 3.5 mmHg (95% CI 1.7-5.4) compared with sitting for 8 h uninterrupted. For participants not taking antihypertensive medications, sitting with 3 min of walking every 30 min decreased systolic blood pressure by 5.0 mmHg (95% CI -7.9 to 2.0) and sitting with 3 min bouts light-intensity exercise while standing every 30 min decreased systolic blood pressure by 4.2 mmHg (95% CI -7.2 to -1.3) compared with sitting for 8 h uninterrupted. There was no effect of condition on diastolic blood pressure (p = 0.45) or plasma fibrinogen levels (p = 0.91). CONCLUSION: Frequent, short bouts of light-intensity phys

Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke. Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset. Results: Over the study period, 13 patients were successfully tested within a week of stroke (baseline NIHSS 10, range 7-16). Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges. Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.