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Background Return to work (RTW) is achieved by less than 50% of stroke survivors. The rising incidence of stroke among younger people, the UK economic forecast, and clinical drivers highlight the need for stroke survivors to receive support with RTW. However, evidence for this type of support is lacking. This randomised controlled trial (RCT) will investigate whether Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care (UC) (i.e. usual NHS rehabilitation) is more clinically and cost-effective for supporting post-stroke RTW, than UC alone. Methods Seven hundred sixty stroke survivors and their carers will be recruited from approximately 20 NHS stroke services. A 5:4 allocation ratio will be employed to randomise participants to receive ESSVR plus UC, or UC alone. The individually tailored ESSVR intervention will commence within 12 weeks of stroke onset and be delivered for up to 12 months as necessary by trained RETAKE occupational therapists in the community, participants’ homes or workplaces, and outpatient/inpatient therapy settings, via telephone, email, or SMS text message. Outcome data will be collected via self-report questionnaires administered by post or online at 3, 6, and 12 months follow-up. The primary outcome will be self-reported RTW and job retention at 12 months (minimum 2 h/week). Secondary outcomes will include mood, function, participation, health-related quality of life, confidence, intervention compliance, health and social care resource use, and mortality. An embedded economic evaluation will estimate cost-effectiveness and cost-utility analyses from National Health Service (NHS) and Personal Social Services (PSS) perspectives. An embedded process evaluation will employ a mixed methods approach to explore ESSVR implementation, contextual factors linked to outcome variation, and factors affecting NHS roll-out. Discussion This article describes the protocol for a multi-centre RCT evaluating the clinical- and cost-effectiveness of an early vocational rehabilitation intervention aimed at supporting adults to return to work following a stroke. Evidence favouring the ESSVR intervention would support its roll-out in NHS settings. Trial registration ISRCTN, ISRCTN12464275 . Registered on 26 February 2018.

ObjectivesThis mixed-method process evaluation underpinned by normalisation process theory aims to measure fidelity to the intervention, understand the social and structural context in which the intervention is delivered and identify barriers and facilitators to intervention implementation.SettingRETurn to work After stroKE (RETAKE) is a multicentre individual patient randomised controlled trial to determine whether Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care is a clinically and cost-effective therapy to facilitate return to work after stroke, compared with usual care alone. This protocol paper describes the embedded process evaluation.Participants and outcome measuresIntervention training for therapists will be observed and use of remote mentor support reviewed through documentary analysis. Fidelity will be assessed through participant questionnaires and analysis of therapy records, examining frequency, duration and content of ESSVR sessions. To understand the influence of social and structural contexts, the process evaluation will explore therapists’ attitudes towards evidence-based practice, competency to deliver the intervention and evaluate potential sources of contamination. Longitudinal case studies incorporating non-participant observations will be conducted with a proportion of intervention and usual care participants. Semistructured interviews with stroke survivors, carers, occupational therapists, mentors, service managers and employers will explore their experiences as RETAKE participants. Analysis of qualitative data will draw on thematic and framework approaches. Quantitative data analysis will include regression models and descriptive statistics. Qualitative and quantitative data will be independently analysed by process evaluation and Clinical Trials Research Unit teams, respectively. Linked data, for example, fidelity and describing usual care will be synthesised by comparing and integrating quantitative descriptive data with the qualitative findings.Ethics and disseminationApproval obtained through the East Midlands—Nottingham 2 Research Ethics Committee (Ref: 18/EM/0019) and the National Health ServiceResearch Authority. Dissemination via journal publications, stroke conferences, social media and meetings with national Stroke clinical leads.Trial registration numberISRCTN12464275.

Early years practitioners know what parents are reminded of every Christmas Day--it does not matter how long families spend carefully selecting the presents, the children are likely to spend longer playing with the empty boxes! Children are fascinated with boxes and practitioners can capitalise on this and support early mathematical development with this free resource. Boxes also lend themselves to the element of surprise. In this article, the author describes how to make the mathematical most of boxes with young children. She presents activities and experiences using boxes and discusses the importance of open-ended questioning. (Contains 2 resources.)

Discusses the importance of practitioners planning to exploit the motivational potential of the outdoor environment and supporting children's spontaneous learning across all aspects of mathematics. Presents outdoor activities, each of which involves several learning goals across all areas of mathematics. (KHR)

Neurospora crassa has at least seven types of 5S RNA genes (α, β, γ, ε, δ, ζ, and η) with different coding regions. A high resolution gel electrophoresis system was developed to separate minor 5S RNA's from the major 5S RNA (α). A study of several Neurospora crassa strains, four other species in the genus Neurospora, members of two closely related genera, and three distantly related genera demonstrated that 5S RNA heterogeneity is common among fungi. In addition, different 5S RNA's are present in Neurospora ribosomes. The finding that fungal ribosomes are structurally heterogeneous suggests that ribosomes may be functionally heterogeneous as well.

We describe two unusual 5S RNA regions from Neurospora crassa that are tightly linked. Sequence analysis suggests that these genes or pseudogenes, which we designate zeta (ζ ) and eta (η ), arose by a 794-base-pair tandem duplication followed by hundreds of exclusively cytosine to thymine mutations. The duplication was most likely generated by nonhomologous recombination involving a DNA segment having a striking purine-pyrimidine strand asymmetry. Restriction analysis of genomic DNA from tissue grown in the presence or absence of 5-azacytidine indicates that many, and perhaps all, cytosines in the duplicated region are methylated in most cells. This is in contrast to the situation typically observed in eukaryotes, where 5-methylcytosine is found only at positions one or two nucleotides preceding guanine residues. No DNA methylation was detected in the unique DNA flanking the ζ -η duplication. Thus the ``signal'' for methylation may be the duplication itself. The numerous transition mutations in this region probably occurred by deamination of 5-methylcytosines. Our results suggest that DNA methylation can have important evolutionary consequences in eukaryotes.

Background: Return to work (RTW) is achieved by less than 50% of stroke survivors. The rising incidence of stroke among younger people, the UK economic forecast, and clinical drivers highlight the need for stroke survivors to receive support with RTW. However, evidence for this type of support is lacking. This randomised controlled trial (RCT) will investigate whether Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care (UC) (i.e., usual NHS rehabilitation) is more clinically and cost effective for supporting post-stroke RTW, than UC alone. Methods: 760 stroke survivors and their carers will be recruited from approximately 20 NHS stroke services. A 5:4 allocation ratio will be employed to randomise participants to receive ESSVR plus UC, or UC alone. The individually tailored ESSVR intervention will commence within 12 weeks of stroke onset and be delivered for up to 12 months as necessary by trained RETAKE occupational therapists in the community, participants’ homes or workplaces, outpatient/inpatient therapy settings, via telephone, email or SMS text message. Outcome data will be collected via self-report questionnaires administered by post or online at 3, 6, and 12 months follow-up. The primary outcome will be self-reported RTW and job retention at 12 months (minimum 2 hours/week). Secondary outcomes will include: mood; function; participation; health-related quality of life; confidence; intervention compliance; health and social care resource use; and mortality. An embedded economic evaluation will estimate cost-effectiveness and cost-utility analyses from National Health Service (NHS) and Personal Social Services (PSS) perspectives. An embedded process evaluation will employ a mixed methods approach to explore ESSVR implementation, contextual factors linked to outcome variation, and factors affecting NHS roll-out. Discussion: This article describes the protocol for a multi-centre RCT evaluating the clinical- and cost-effectiveness of an early vocational rehabilitation intervention aimed at supporting adults to return to work following a stroke. Evidence favouring the ESSVR intervention would support its roll-out in NHS settings. Trial registration: ISRCTN, ISRCTN12464275. Registered on 26th February 2018, http://www.isrctn.com/ISRCTN12464275.