Chemical and genetic rescue of in vivo progranulin-deficient lysosomal and autophagic defects.

In 2006, GRN mutations were first linked to frontotemporal dementia (FTD), the leading cause of non-Alzheimer dementias. While much research has been dedicated to understanding the genetic causes of the disease, our understanding of the mechanistic impacts of GRN deficiency has only recently begun to take shape. With no known cure or treatment available for GRN-related FTD, there is a growing need to rapidly advance genetic and/or small-molecule therapeutics for this disease. This issue is complicated by the fact that, while lysosomal dysfunction seems to be a key driver of pathology, the mechanisms linking a loss of GRN to a pathogenic state remain unclear. In our attempt to address these key issues, we have turned to the nematode, Caenorhabditis elegans, to model, study, and find potential therapies for GRN-deficient FTD. First, we show that the loss of the nematode GRN ortholog, pgrn-1, results in several behavioral and molecular defects, including lysosomal dysfunction and defects in autophagic flux. Our investigations implicate the sphingolipid metabolic pathway in the regulation of many of the in vivo defects associated with pgrn-1 loss. Finally, we utilized these nematodes as an in vivo tool for high-throughput drug screening and identified two small molecules with potential therapeutic applications against GRN/pgrn-1 deficiency. These compounds reverse the biochemical, cellular, and functional phenotypes of GRN deficiency. Together, our results open avenues for mechanistic and therapeutic research into the outcomes of GRN-related neurodegeneration, both genetic and molecular.

Assessing the role of Piscine orthoreovirus in disease and the associated risk for wild Pacific salmon.

This paper is a response to Polinski, M. P. et al. Innate antiviral defense demonstrates high energetic efficiency in a bony fish. BMC Biology 19, 138 (2021). https://doi.org/10.1186/s12915-021-01069-2.

Mood, Activity Participation, and Leisure Engagement Satisfaction (MAPLES): results from a randomised controlled pilot feasibility trial for low mood in acquired brain injury.

BACKGROUND: Acquired brain injury (ABI) is linked to increased depression risk. Existing therapies for depression in ABI (e.g., cognitive behavioural therapy) have mixed efficacy. Behavioural activation (BA), an intervention that encourages engaging in positively reinforcing activities, shows promise. The primary aims were to assess feasibility, acceptability, and potential efficacy of two 8-week BA groups. METHODS: Adults (≥ 18 years) recruited from local ABI services, charities, and self-referral via social media were randomised to condition. The Activity Planning group (AP; "traditional" BA) trained participants to plan reinforcing activities over 8 weeks. The Activity Engagement group (AE; "experiential" BA) encouraged engagement in positive activities within session only. Both BA groups were compared to an 8-week Waitlist group (WL). The primary outcomes, feasibility and acceptability, were assessed via recruitment, retention, attendance, and qualitative feedback on groups. The secondary outcome, potential efficacy, was assessed via blinded assessments of self-reported activity levels, depression, and anxiety (at pre- and post-intervention and 1 month follow-up) and were compared across trial arms. Data were collected in-person and remotely due to COVID-19. RESULTS: N = 60 participants were randomised to AP (randomised n = 22; total n = 29), AE (randomised n = 22; total n = 28), or re-randomised following WL (total n = 16). Whether in-person or remote, AP and AE were rated as similarly enjoyable and helpful. In exploring efficacy, 58.33% of AP members had clinically meaningful activity level improvements, relative to 50% AE and 38.5% WL. Both AP and AE groups had depression reductions relative to WL, but only AP participants demonstrated anxiety reductions relative to AE and WL. AP participants noted benefits of learning strategies to increase activities and learning from other group members. AE participants valued social discussion and choice in selecting in-session activities. CONCLUSIONS: Both in-person and remote group BA were feasible and acceptable in ABI. Though both traditional and experiential BA may be effective, these may have different mechanisms. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03874650. Protocol version 2.3, May 26 2020.

Socially active neighborhoods: construct operationalization for aging in place, health promotion and psychometric testing.

From the year 2003 when the first walkability scale was published to date, person-environment fit models and empirical research, some of which was published in Health Promotion International, have encapsulated healthy communities in 'neighborhood walkability'. While there is no doubt that neighborhood walkability positively influences health-seeking behaviors and health, recent models suggest that their measurement and conceptualization have not emphasized the role played by psychosocial and personal factors in aging in place. Thus, the development of scales measuring human ecosystem factors has not recognized all critical factors suited for older adults. In this paper, we aim to draw on relevant literature to frame a more holistic construct, hereby referred to as Socially Active Neighborhoods (SAN), that would better support aging in place in older populations. Through a narrative review based on a systematic search of the literature, we define the scope of SAN and delineate some contextual implications for gerontology, health promotion and psychometric testing. SAN, unlike neighborhood walkability in its current measurement and conceptualization, incorporates critical theory-informed psychosocial factors (i.e. safety and disability friendliness of neighborhood infrastructure) that can encourage older adults with physiological and cognitive limitations to maintain physical and social activities as well as health in later life. The SAN is the result of our adaptation of key person-environment models, including the Context Dynamics in Aging (CODA) framework, that recognizes the role of context in healthy aging.

A Systematic Review of the Validity and Reliability of Assessment Tools for Executive Function and Adaptive Function Following Brain Pathology among Children and Adolescents in Low- and Middle-Income Countries.

Minimal but increasing number of assessment instruments for Executive functions (EFs) and adaptive functioning (AF) have either been developed for or adapted and validated for use among children in low and middle income countries (LAMICs). However, the suitability of these tools for this context is unclear. A systematic review of such instruments was thus undertaken. The Systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist (Liberati et al., in BMJ (Clinical Research Ed.), 339, 2009). A search was made for primary research papers reporting psychometric properties for development or adaptation of either EF or AF tools among children in LAMICs, with no date or language restrictions. 14 bibliographic databases were searched, including grey literature. Risk of bias assessment was done following the COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) guidelines (Mokkink et al., in Quality of Life Research, 63, 32, 2014). For EF, the Behaviour Rating Inventory of Executive Functioning (BRIEF- multiple versions), Wisconsin Card Sorting Test (WCST), Go/No-go and the Rey-Osterrieth complex figure (ROCF) were the most rigorously validated. For AFs, the Vineland Adaptive Behaviour Scales (VABS- multiple versions) and the Child Function Impairment Rating Scale (CFIRS- first edition) were most validated. Most of these tools showed adequate internal consistency and structural validity. However, none of these tools showed acceptable quality of evidence for sufficient psychometric properties across all the measured domains, particularly so for content validity and cross-cultural validity in LAMICs. There is a great need for adequate adaptation of the most popular EF and AF instruments, or alternatively the development of purpose-made instruments for assessing children in LAMICs.Systematic Review Registration numbers: CRD42020202190 (EF tools systematic review) and CRD42020203968 (AF tools systematic review) registered on PROSPERO website ( https://www.crd.york.ac.uk/prospero/ ).

Assessment Tools for Executive Function and Adaptive Function Following Brain Pathology Among Children in Developing Country Contexts: a Scoping Review of Current Tools.

Several tools have been developed to assess executive function (EFs) and adaptive functioning, although in mainly Western populations. Information on tools for low-and-middle-income country children is scanty. A scoping review of such instruments was therefore undertaken.We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis- Scoping Review extension (PRISMA-ScR) checklist (Tricco et al., in Annals of Internal Medicine 169(7), 467-473, 2018). A search was made for primary research papers of all study designs that focused on development or adaptation of EF or adaptive function tools in low-and-middle-income countries, published between 1st January 1894 to 15th September 2020. 14 bibliographic databases were searched, including several non-English databases and the data were independently charted by at least 2 reviewers.The search strategy identified 5675 eligible abstracts, which was pruned down to 570 full text articles. These full-text articles were then manually screened for eligibility with 51 being eligible. 41 unique tools coming in 49 versions were reviewed. Of these, the Behaviour Rating Inventory of Executive Functioning (BRIEF- multiple versions), Wisconsin Card Sorting Test (WCST), Go/No-go and the Rey-Osterrieth complex figure (ROCF) had the most validations undertaken for EF tests. For adaptive functions, the tools with the most validation studies were the Vineland Adaptive Behaviour Scales (VABS- multiple versions) and the Child Function Impairment Rating Scale (CFIRS- first edition).There is a fair assortment of tests available that have either been developed or adapted for use among children in developing countries but with limited range of validation studies. However, their psychometric adequacy for this population was beyond the scope of this paper.

Client experiences with holistic neuropsychological rehabilitation: "It is an ongoing process".

The effectiveness of holistic neuropsychological rehabilitation for people with acquired brain injury has previously been demonstrated by means of standardized and routinely administered outcome measures. However, the most important outcomes from the perspective of former clients are largely unknown. This study explored the experience of participating in a holistic neuropsychological rehabilitation programme by conducting three focus groups with twelve former clients who had sustained a brain injury. Data were transcribed verbatim and analysed using thematic analysis. "It is an ongoing process" emerged as the overarching theme for the experience of recovery from brain injury. Four subthemes, or phases, were identified. Participants went through (1) a phase of confrontation, after which they (2) trained their skills and strategies, and (3) experimented with these in daily life. In the end, clients reached a phase of (4) coming to terms with their injury. Participants described increased levels of self-esteem, sense of competence, and adaptation as the most important outcomes of the programme, as these factors helped them regain a sense of identity. The results indicate that including these factors in outcome evaluations of complex interventions after brain injury may be important as they appear essential for capturing the client's perspective on change.

A randomized control trial of the effects of home-based online attention training and working memory training on cognition and everyday function in a community stroke sample.

Cognitive difficulties are common following stroke and can have widespread impacts on everyday functioning. Technological advances offer the possibility of individualized cognitive training for patients at home, potentially providing a low-cost, low-intensity adjunct to rehabilitation services. Using this approach, we have previously demonstrated post-training improvements in attention and everyday functioning in fronto-parietal stroke patients. Here we examine whether these benefits are observed more broadly in a community stroke sample. Eighty patients were randomized to either 4 weeks of online adaptive attention training (SAT), working memory training (WMT) or waitlist (WL). Cognitive and everyday function measures were collected before and after the intervention, and after 3 months. During training, weekly measures of patients' subjective functioning were collected. The training was well received and compliance good. No differences in our primary end-point, spatial bias, or other cognitive functions were observed. However, on patient-reported outcomes, SAT participants showed greater levels of improvement in everyday functioning than WMT or WL participants. In line with our previous work, everyday functioning improvements were greatest for patients with spatial impairments and those who received SAT training. Whether attention training can be recommended for stroke survivors depends on whether cognitive test performance or everyday functioning is considered more relevant.

Bias in self-reported parasite data from the salmon farming industry.

Many industries are required to monitor themselves in meeting regulatory policies intended to protect the environment. Self-reporting of environmental performance can place the cost of monitoring on companies rather than taxpayers, but there are obvious risks of bias, often addressed through external audits or inspections. Surprisingly, there have been relatively few empirical analyses of bias in industry self-reported data. Here, we test for bias in reporting of environmental compliance data using a unique data set from Canadian salmon farms, where companies monitor the number of parasitic sea lice on fish in open sea pens, in order to minimize impacts on wild fish in surrounding waters. We fit a hierarchical population-dynamics model to these sea-louse count data using a Bayesian approach. We found that the industry's monthly counts of two sea-louse species, Caligus clemensi and Lepeophtheirus salmonis, increased by a factor of 1.95 (95% credible interval: 1.57, 2.42) and 1.18 (1.06, 1.31), respectively, in months when counts were audited by the federal fisheries department. Consequently, industry sea-louse counts are less likely to trigger costly but mandated delousing treatments intended to avoid sea-louse epidemics in wild juvenile salmon. These results highlight the potential for combining external audits of industry self-reported data with analyses of their reporting to maintain compliance with regulations, achieve intended conservation goals, and build public confidence in the process.

The effectiveness and cost-effectiveness of assistive technology and telecare for independent living in dementia: a randomised controlled trial.

OBJECTIVES: The use of assistive technology and telecare (ATT) has been promoted to manage risks associated with independent living in people with dementia but with little evidence for effectiveness. METHODS: Participants were randomly assigned to receive an ATT assessment followed by installation of all appropriate ATT devices or limited control of appropriate ATT. The primary outcomes were time to institutionalisation and cost-effectiveness. Key secondary outcomes were number of incidents involving risks to safety, burden and stress in family caregivers and quality of life. RESULTS: Participants were assigned to receive full ATT (248 participants) or the limited control (247 participants). After adjusting for baseline imbalance of activities of daily living score, HR for median pre-institutionalisation survival was 0.84; 95% CI, 0.63 to 1.12; P = 0.20. There were no significant differences between arms in health and social care (mean -£909; 95% CI, -£5,336 to £3,345, P = 0.678) and societal costs (mean -£3,545; 95% CI, -£13,914 to £6,581, P = 0.499). ATT group members had reduced participant-rated quality-adjusted life years (QALYs) at 104 weeks (mean - 0.105; 95% CI, -0.204 to -0.007, P = 0.037) but did not differ in QALYs derived from proxy-reported EQ-5D. DISCUSSION: Fidelity of the intervention was low in terms of matching ATT assessment, recommendations and installation. This, however, reflects current practice within adult social care in England. CONCLUSIONS: Time living independently outside a care home was not significantly longer in participants who received full ATT and ATT was not cost-effective. Participants with full ATT attained fewer QALYs based on participant-reported EQ-5D than controls at 104 weeks.

Detecting mental health problems after paediatric acquired brain injury: A pilot Rasch analysis of the strengths and difficulties questionnaire.

The parent-reported Strengths and Difficulties Questionnaire (SDQ-P) is commonly used to assess for mental health problems, but its psychometric properties have not been studied in the paediatric Acquired Brain Injury (ABI) population. This study investigated the properties of the SDQ-P and its subscales in this population using Rasch analysis. One hundred and forty-three SDQ-Ps and 123 Impact Supplements were analyzed. Sixty-nine percent of SDQ-Ps were completed by female carers, 59% of young people were male, and 58% had Traumatic Brain Injury (TBI). In this population the SDQ-P Total Difficulties Scale and the Conduct Problems subscale showed questionable construct validity. The individual subscales and Impact Supplement did not meet the criteria for reliability. Two items had disordered thresholds. The individual subscales showed mistargeting and 13-24% person misfit. Two items were significantly underdiscriminating. There was differential item functioning with age and time post-injury, and local dependence between subscale items. The Total Difficulties scale was multidimensional. The most easily endorsed items were in keeping with common symptoms of brain injury. These findings suggest the SDQ-P in its current form may not be a reliable and valid assessment measure for mental health difficulties in the paediatric ABI population and requires further investigation.

Environmental DNA from multiple pathogens is elevated near active Atlantic salmon farms.

The spread of infection from reservoir host populations is a key mechanism for disease emergence and extinction risk and is a management concern for salmon aquaculture and fisheries. Using a quantitative environmental DNA methodology, we assessed pathogen environmental DNA in relation to salmon farms in coastal British Columbia, Canada, by testing for 39 species of salmon pathogens (viral, bacterial, and eukaryotic) in 134 marine environmental samples at 58 salmon farm sites (both active and inactive) over 3 years. Environmental DNA from 22 pathogen species was detected 496 times and species varied in their occurrence among years and sites, likely reflecting variation in environmental factors, other native host species, and strength of association with domesticated Atlantic salmon. Overall, we found that the probability of detecting pathogen environmental DNA (eDNA) was 2.72 (95% CI: 1.48, 5.02) times higher at active versus inactive salmon farm sites and 1.76 (95% CI: 1.28, 2.42) times higher per standard deviation increase in domesticated Atlantic salmon eDNA concentration at a site. If the distribution of pathogen eDNA accurately reflects the distribution of viable pathogens, our findings suggest that salmon farms serve as a potential reservoir for a number of infectious agents; thereby elevating the risk of exposure for wild salmon and other fish species that share the marine environment.

Evaluation of NeuroPage as a memory aid for people with multiple sclerosis: A randomised controlled trial.

Memory problems are reported in 40%-60% of people with multiple sclerosis (MS). These problems affect independence and may limit the ability to benefit from rehabilitation. Our aim was to evaluate the effectiveness of NeuroPage for people with MS living in the community. A multicentre, single-blind, randomised controlled crossover trial was conducted. The intervention comprised the NeuroPage service, which sends reminder messages to mobile phones at pre-arranged times. In the control condition participants received "non-memory texts", that is, messages not aimed at providing a reminder; for example, supplying news headlines or sport updates. Outcome measures were completed using postal questionnaires after each condition. There were 38 participants aged 28 to 72 (mean 48, SD 11) and 10 (26%) were men. There were no significant differences between NeuroPage and control conditions on the Everyday Memory Questionnaire (p = 0.41, d = 0.02). The number of daily diary items forgotten in the NeuroPage condition was significantly less than in the control (9% vs. 31%, p = 0.01, d = -0.64). Psychological distress was less in the NeuroPage condition than control (p = 0.001, d = -0.84). Further evaluation of the effect on everyday memory is required.

Measurement of everyday dysexecutive symptoms in normal aging with the Greek version of the dysexecutive questionnaire-revised.

The Dysexecutive Questionnaire is a sensitive and ecologically valid measure of everyday dysexecutive symptoms. Recently, a revised version of the tool has been proposed (DEX-R). The current study aimed to examine the factorial validity of the Greek DEX-R, the level of agreement between the self and informant rating versions and the effect of age on each dysexecutive symptoms component. The questionnaire was administered to a sample of older adults (n = 235) and to a sample of informants (n = 187) in the context of the Neurocognitive Study for the Aging in Cyprus. Confirmatory Factor Analysis results showed that dysexecutive symptoms can be grouped into three underlying components or factors: (a) Motivation and Attention, (b) Flexibility, Fluency and Working Memory, and (c) Social Self-Regulation. Overall, the elderly reported more symptoms than their relatives, however the difference was significant only for the Flexibility, Fluency and Working memory factor. In a structural equation model, a weak positive effect of age was observed on the Flexibility, Fluency and Working Memory factor, based on the informant ratings. This study provides empirical evidence about the use of the DEX-R questionnaire in the Greek-speaking elderly population as a valid and reliable measure of everyday dysexecutive symptoms.

Cost of dispersal in a social mammal: body mass loss and increased stress.

Dispersal is a key process influencing the dynamics of socially and spatially structured populations. Dispersal success is determined by the state of individuals at emigration and the costs incurred after emigration. However, quantification of such costs is often difficult, due to logistical constraints of following wide-ranging individuals. We investigated the effects of dispersal on individual body mass and stress hormone levels in a cooperative breeder, the meerkat ( Suricata suricatta). We measured body mass and faecal glucocorticoid metabolite (fGCM) concentrations from 95 dispersing females in 65 coalitions through the entire dispersal process. Females that successfully settled lost body mass, while females that did not settle but returned to their natal group after a short period of time did not. Furthermore, dispersing females had higher fGCM levels than resident females, and this was especially pronounced during the later stages of dispersal. By adding information on the transient stage of dispersal and by comparing dispersers that successfully settled to dispersers that returned to their natal group, we expand on previous studies focusing on the earlier stages of dispersal. We propose that body mass and stress hormone levels are good indicators to investigate dispersal costs, as these traits often play an important role in mediating the effects of the environment on other life-history events and individual fitness.

Salmonid species diversity predicts salmon consumption by terrestrial wildlife.

Resource waves-spatial variation in resource phenology that extends feeding opportunities for mobile consumers-can affect the behaviour and productivity of recipient populations. Interspecific diversity among Pacific salmon species (Oncorhynchus spp.) creates staggered spawning events across space and time, thereby prolonging availability to terrestrial wildlife. We sought to understand how such variation might influence consumption by terrestrial predators compared with resource abundance and intra- and interspecific competition. Using stable isotope analysis, we investigated how the proportion of salmon in the annual diet of male black bears (Ursus americanus; n = 405) varies with species diversity and density of spawning salmon biomass, while also accounting for competition with sympatric black and grizzly bears (U. arctos horribilis), in coastal British Columbia, Canada. We found that the proportion of salmon in the annual diet of black bears was ≈40% higher in the absence of grizzly bears, but detected little effect of relative black bear density and salmon biomass density. Rather, salmon diversity had the largest positive effect on consumption. On average, increasing diversity from one salmon species to ~four (with equal biomass contributions) approximately triples the proportion of salmon in diet. Given the importance of salmon to bear life histories, this work provides early empirical support for how resource waves may increase the productivity of consumers at population and landscape scales. Accordingly, terrestrial wildlife management might consider maintaining not only salmon abundance but also diversity.

Distribution of the EQ-5D-5L Profiles and Values in Three Patient Groups.

BACKGROUND: The distribution of EQ-5D-3L values (health state profiles, weighted by value sets) often shows two distinct groups, arising from both the distribution of profiles and the characteristics of value sets. To date, there is little evidence about the distribution of EQ-5D-5L values. OBJECTIVES: To explore the distribution of EQ-5D-5L profiles; to compare the distributions of EQ-5D-5L values arising from the English value set (EVS) and a 'mapped' value set (MVS); and to develop further the methods used to investigate clustering within EQ-5D data. METHODS: We obtained data from Cambridgeshire Community Services NHS Trust containing EQ-5D-5L profiles before treatment for three patient groups: community rehabilitation (N=6919); musculoskeletal physiotherapy (N=19999); and specialist nursing services (N=3366). Values were calculated using the EVS and MVS. Clusters were examined using the k-means method and Calinski-Harabasz pseudo-F index stopping rule. RESULTS: We found no evidence for clustering of EQ-5D-5L values arising from the classification system and no strong or consistent evidence of clustering arising from the EVS. There was clearer evidence of clustering using the MVS, with two being the optimal number of clusters. The clusters that were found for the EVS were very different from the MVS clusters. CONCLUSIONS: Unlike the EQ-5D-3L, clustering of EQ-5D-5L values does not seem to be driven by clustering of its profile. This suggests the EQ-5D-5L is superior in that it is less likely to generate artefactual clusters - however, clusters may still result from using value sets such as MVS that have the tendency to generate them.

Matrix Models of Hierarchical Demography: Linking Group- and Population-Level Dynamics in Cooperative Breeders.

For highly social species, population dynamics depend on hierarchical demography that links local processes, group dynamics, and population growth. Here, we describe a stage-structured matrix model of hierarchical demography, which provides a framework for understanding social influences on population change. Our approach accounts for dispersal and affords insight into population dynamics at multiple scales. The method has close parallels to integral projection models but focuses on a discrete characteristic (group size). Using detailed long-term records for meerkats (Suricata suricatta), we apply our model to explore patterns of local density dependence and implications of group size for group and population growth. Taking into account dispersers, the model predicts a per capita growth rate for social groups that declines with group size. It predicts that larger social groups should produce a greater number of new breeding groups; thus, dominant breeding females (responsible for most reproduction) are likely to be more productive in larger groups. Considering the potential for future population growth, larger groups have the highest reproductive value, but per capita reproductive value is maximized for individuals in smaller groups. Across a plausible range of dispersal conditions, meerkats' long-run population growth rate is maximized when individuals form groups of intermediate size.

Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease.

Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. Progranulin consists of seven and a half, tandemly repeated, non-identical copies of the 12 cysteine granulin motif. Many cellular processes and diseases are associated with this unique pleiotropic factor that include, but are not limited to, embryogenesis, tumorigenesis, inflammation, wound repair, neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to frontotemporal lobar degeneration, a progressive neuronal atrophy that presents in patients as frontotemporal dementia. Frontotemporal dementia is an early onset form of dementia, distinct from Alzheimer's disease. The GRN-related form of frontotemporal lobar dementia is a proteinopathy characterized by the appearance of neuronal inclusions containing ubiquitinated and fragmented TDP-43 (encoded by TARDBP). The neurotrophic and neuro-immunomodulatory properties of progranulin have recently been reported but are still not well understood. Gene delivery of GRN in experimental models of Alzheimer's- and Parkinson's-like diseases inhibits phenotype progression. Here we review what is currently known concerning the molecular function and mechanism of action of progranulin in normal physiological and pathophysiological conditions in both in vitro and in vivo models. The potential therapeutic applications of progranulin in treating neurodegenerative diseases are highlighted.

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial.

OBJECTIVE: To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. DESIGN: A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. SETTING: Participants' homes across Cambridgeshire, UK. SUBJECTS: Eleven people with stroke and arm hemiparesis, 3-60 months post stroke, following discharge from community rehabilitation. INTERVENTIONS: Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. MAIN MEASURES: Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. RESULTS: A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. CONCLUSION: It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT 02310438.