“This is pretend. We are just playing.” Exploring young children’s imaginative play with, and educators’ provision of, digital technologies in play-based settings.

Digital technologies have become commonplace in nearly all areas of the modern life in Western society. Mobile phone users now have the ability to watch movies, surf the internet and perform all the functionalities of a computer on increasingly smaller devices. Children are capable of not only taking photos and movies, but they can successfully upload them to social media. They now have an online presence from a very early age, sometimes even before they are born. What does this mean for early childhood educational settings, where play is valued as the way children learn? Children are arriving at these services with a wide range of prior experiences including more technical knowledge than ever before, and sometimes, more than their educators. The early childhood field began by debating the appropriateness of using technologies with young children, but current literature has moved on to now focus on exploring their engagement with technologies, and on the positive benefits of building children’s knowledge of technologies, prior to formal schooling. What is not clearly defined is how children engage with these devices when they are provided in play-based, learning settings. Educators often struggle to integrate these technologies into their play-based pedagogies, and to support children’s meaning making when their play involves these devices. While some targeted professional development for educators aims to build their knowledge around how to provide technologies for young children, these efforts have not been very effective when integrating them into play-based pedagogy. What is needed is greater understanding of how to provide technologies in meaningful ways, and how to implement child-focused pedagogies incorporating technologies that support children’s play and learning. This thesis aims to explore the integration between children’s imaginative play with digital technologies, and the influences on educators’ provision of these devices in play-based settings. The research was conducted in two kindergarten settings, in suburbs of Melbourne, Australia. The children were aged four to six years and were attending kindergarten in the year prior to school entry. An ethnographic study was conducted over a 12-week period, with data being collected via video recordings, photographs, observations, conversations with children, interviews with educators and a researcher journal. The first contribution to knowledge that this thesis makes is the introduction of the Imaginative Affordance Framework, which combines Vygotsky’s (1966) concepts of mediation and imagination with Gibson’s (1979) concept of affordance. The framework was used to analyse the data collected and establish the findings related to the children’s imaginative play with digital technologies and to understand the educators’ provision of these devices. The findings were presented and discussed as six paradoxes: working technologies versus non-working technologies; solitary individuals working with devices versus groups of children on devices; play-based, child centred programmes versus adult controlled programmes; nature discourse versus technologies as not natural; traditional kindergarten activities versus newer technological activities; and, children learning to navigate the rules pertaining to working technologies versus their desire to play according to their own volition. Based on the findings three recommendations were presented. These related to the children, the educators and the wider community and policy makers. The second contribution to knowledge filled the gap in current understanding, established in the literature review, around how children engage with digital technologies in their imaginative play, influenced by what and how the devices are provided by their educators. The reasons behind the educators’ provision are discussed and their position as neoliberal subjects is recognised and explored. A diagram of provision is presented and suggestions for professional learning to address the intervention points within the diagram are made. The thesis concludes with recommendations of potential research that would further extend the knowledge base of this topic

The MAGEC System for Spinal Lengthening in Children with Scoliosis: A NICE Medical Technology Guidance

Scoliosis—structural lateral curvature of the spine—affects around four children per 1,000. The MAGEC system comprises a magnetically distractible spinal rod implant and an external remote controller, which lengthens the rod; this system avoids repeated surgical lengthening. Rod implants brace the spine internally and are lengthened as the child grows, preventing worsening of scoliosis and delaying the need for spinal fusion. The Medical Technologies Advisory Committee at the National Institute for Health and Care Excellence (NICE) selected the MAGEC system for evaluation in a NICE medical technologies guidance. Six studies were identified by the sponsor (Ellipse Technologies Inc.) as being relevant to the decision problem. Meta-analysis was used to compare the clinical evidence results with those of one conventional growth rod study, and equal efficacy of the two devices was concluded. The key weakness was selection of a single comparator study. The External Assessment Centre (EAC) identified 16 conventional growth rod studies and undertook meta-analyses of relevant outcomes. Its critique highlighted limitations around study heterogeneity and variations in baseline characteristics and follow-up duration, precluding the ability to draw firm conclusions. The sponsor constructed a de novo costing model showing that MAGEC rods generated cost savings of £9,946 per patient after 6 years, compared with conventional rods. The EAC critiqued and updated the model structure and inputs, calculating robust cost savings of £12,077 per patient with MAGEC rods compared with conventional rods over 6 years. The year of valuation was 2012. NICE issued a positive recommendation as supported by the evidence (Medical Technologies Guidance 18)

Challenges, barriers and strategies for engaging in level 7 apprenticeship studies

This study explores the lived experience of apprentices on a degree-level programme and their perceptions of how elements of apprenticeship study that aren’t components of traditional degree study – i.e. off-the- job training – impact their learner journey. This article undertakes a thematic analysis following qualitative interviews with eleven apprentices, who are early-career academic professionals nearing the end of their apprenticeships. Key findings offer a mixed picture, and suggest that the study habits and preferences of apprentices are personal to individuals and are impacted on by employment workload and access to off-the-job study time. Apprentices indicate that many factors encroach on their ability to utilise the allocated off-the-job study time, primarily the ability to be released from employed work and conflicting priorities around meeting study, business, and personal needs. Apprentices suggest that in reality it is almost impossible for them to spend 20% of their working time on their studies. Recommendations are offered to both institutions and individuals, regarding the need for sound dialogue and the removal of barriers to ensure that apprentices can meet the contractual requirements of apprenticeship stud

Systematic Review of Economic Models Used to Compare Techniques for Detecting Peripheral Arterial Disease

Background and objective Peripheral arterial disease (PAD) is a common condition, in which atherosclerotic narrowing in the arteries restricts blood supply to the leg muscles. In order to support future model-based economic evaluations comparing methods of diagnosis in this area, a systematic review of economic modelling studies was conducted. Methods A systematic literature review was performed in June 2017 to identify model-based economic evaluations of diagnostic tests to detect PAD, with six individual databases searched. The review was conducted in accordance with the methods outlined in the Centre for Reviews and Dissemination’s guidance for undertaking reviews in healthcare, and appropriate inclusion criteria were applied. Relevant data were extracted, and studies were quality assessed. Results Seven studies were included in the final review, all of which were published between 1995 and 2014. There was wide variation in the types of diagnostic test compared. The majority of the studies (six of seven) referenced the sources used to develop their model, and all studies stated and justified the structural assumptions. Reporting of the data within the included studies could have been improved. Only one identified study focused on the cost-effectiveness of a test typically used in primary care. Conclusions This review brings together all applied modelling methods for tests used in the diagnosis of PAD, which could be used to support future model-based economic evaluations in this field. The limited modelling work available on tests typically used for the detection of PAD in primary care, in particular, highlights the importance of future work in this area

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy

<b>Background:</b> Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2–3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.<p></p> <b>Objective:</b> To undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC.<p></p> <b>Design, setting, and participants:</b> RNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes.<p></p> <b>Outcome measurements and statistical analysis:</b> We searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in a CRPC in vitro cell line model.<p></p> <b>Results and limitations:</b> We identified ADT-regulated signalling pathways, including the Wnt/β-catenin signalling pathway, and observed overexpression of β-catenin in a subset of CRPC by immunohistochemistry. We validated 6 of 12 (50%) pathway members by qRT-PCR on LNCaP/LNCaP-AI cell RNAs, of which 4 (67%) demonstrated expression changes consistent with RNA-seq data. We show that the tankyrase inhibitor XAV939 (which promotes β-catenin degradation) reduced androgen-independent LNCaP-AI cell line growth compared with androgen-responsive LNCaP cells via an accumulation of cell proportions in the G0/G1 phase and reduction in the S and G2/M phases. Our biopsy protocol did not account for tumour heterogeneity, and pathway inhibition was limited to pharmacologic approaches.<p></p> <b>Conclusions:</b> RNA-seq of paired PCa samples revealed ADT-regulated signalling pathways. Proof-of-principle inhibition of the Wnt/β-catenin signalling pathway specifically delays androgen-independent PCa cell cycle progression and proliferation and warrants further investigation as a potential target for therapy for CRPC.<p></p&gt

Greater understanding of normal hip physical function may guide clinicians in providing targeted rehabilitation programmes

Objectives: This study investigated tests of hip muscle strength and functional performance. The specific objectives were to: (i) establish intra- and inter-rater reliability; (ii) compare differences between dominant and non-dominant limbs; (iii) compare agonist and antagonist muscle strength ratios; (iv) compare differences between genders; and (v) examine relationships between hip muscle strength, baseline measures and functional performance. Design: Reliability study and cross-sectional analysis of hip strength and functional performance. Methods: In healthy adults aged 18-50. years, normalised hip muscle peak torque and functional performance were evaluated to: (i) establish intra-rater and inter-rater reliability; (ii) analyse differences between limbs, between antagonistic muscle groups and genders; and (iii) associations between strength and functional performance. Results: Excellent reliability (intra-rater ICC = 0.77-0.96; inter-rater ICC = 0.82-0.95) was observed. No difference existed between dominant and non-dominant limbs. Differences in strength existed between antagonistic pairs of muscles: hip abduction was greater than adduction (p < 0.001) and hip ER was greater than IR (p < 0.001). Men had greater ER strength (p = 0.006) and hop for distance (p < 0.001) than women. Strong associations were observed between measures of hip muscle strength (except hip flexion) and age, height, and functional performance. Conclusions: Deficits in hip muscle strength or functional performance may influence hip pain. In order to provide targeted rehabilitation programmes to address patient-specific impairments, and determine when individuals are ready to return to physical activity, clinicians are increasingly utilising tests of hip strength and functional performance. This study provides a battery of reliable, clinically applicable tests which can be used for these purposes

Protecting older people living in care homes from COVID-19 : a protocol for a mixed-methods study to understand the challenges and solutions to implementing social distancing and isolation.

Older people living in residential and nursing care homes often have complex needs and are at high risk of poor health outcomes and mortality, especially if they contract COVID-19. Care homes use infection prevention and control measures such as social distancing and isolating residents to protect them from COVID-19. The care home sector has stated that implementing social distancing and isolation when caring for residents is a significant challenge. This paper presents the protocol of a mixed-methods study to explore and understand the real-life experiences of implementing social distancing and isolation of residents in care homes for older people from the perspective of residents, families/friends and staff working in and with care homes. The study aims to develop a toolkit of resources for health and care delivery now and for future outbreaks of infectious diseases. The study will be conducted in three phases. Phase 1 is a rapid review of evidence to collate knowledge on the mechanisms and measures used by care homes and long-term facilities to socially distance and isolate older people or control the spread of other infectious and contagious diseases. The review results will contribute to participant interviews in phase 2 and toolkit development in phase 3. Phase 2 will involve case studies with six care homes in England, involving the conduct of individual interviews with residents, families and friends, and staff, collection of care home policies and protocols related to social distancing and isolation for residents, and routinely collected care home data. A focus group with a purposive sample of external key informants will also be conducted. Phase 3, synthesising findings from phases 1 and 2, will inform the codesign of a toolkit of resources for residents, families/friends and care homes. The study has been approved by Coventry and Warwick Research Ethics Committee (20/WM/0318). To maximise impact, we will work closely with the Study Committees and the Patient and Public Involvement group to ensure the findings reach key stakeholders, including residents, families/friends, care homes, commissioners and organisations representing care home providers. We will disseminate the study outputs in peer-reviewed and professional journals, at professional conferences and via other knowledge transfer activities with the care home sector, and resident and carer organisations. The toolkit comprising evidence-informed guidance and resources and a mosaic film will be hosted on a project webpage. This project is funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research Programme (Project reference NIHR132541). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. CRD42021226734. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Social Distancing and Isolation Strategies to Prevent and Control the Transmission of COVID-19 and Other Infectious Diseases in Care Homes for Older People: An International Review.

Older people living in care homes are at high risk of poor health outcomes and mortality if they contract COVID-19 or other infectious diseases. Measures used to protect residents include social distancing and isolation, although implementation is challenging. This review aimed to assess the social distancing and isolation strategies used by care homes to prevent and control the transmission of COVID-19 and other infectious diseases. Seven electronic databases were searched: Medline, CINAHL, Embase, PsycINFO, HMIC, Social Care Online, and Web of Science Core Collection. Grey literature was searched using MedRxiv, PDQ-Evidence, NICE Evidence Search, LTCCovid19.org and TRIP. Extracted data were synthesised using narrative synthesis and tabulation. 103 papers were included (10 empirical studies, seven literature reviews, and 86 policy documents). Strategies used to prevent and control the transmission of COVID-19 and other infectious diseases included social distancing and isolation of residents and staff, zoning and cohorting of residents, restriction of resident movement/activities, restriction of visitors and restriction of staff working patterns. This review demonstrates a lack of empirical evidence and the limited nature of policy documentation around social distancing and isolation measures in care homes. Evaluative research on these interventions is needed urgently, focusing on the well-being of all residents, particularly those with hearing, vision or cognitive impairments

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy