A review of the constraints, limitations and success of Homecoming Scotland 2009

The aim of this review is to provide insight and analysis of a government tourism initiative within the geographic context of Scotland. It highlights the centrality of public-private partnership and the catalytic role of key government agencies in channelling investment, energies, events and marketing effort for a nationally focused tourism theme of Homecoming Scotland 2009 (HS09). The review also delves below the public relations veneer of many such activities to uncover the political debates and controversies, and the wider issues that may have detracted from the degree of success achieved by the initiative

Non traditional but extremely powerful

A short piece on the nature of research management in the arts and creative practice discipline

Investigation of the inter- and intra-scanner reproducibility and repeatability of radiomics features in T1-weighted brain MRI

Open Access via the Wiley Agreement Acknowledgments This work was supported by the Industrial Centre for AI Research in digital Diagnostics (iCAIRD) which was funded by Innovate UK on behalf of UK Research and Innovation (UKRI) (project number: 104690) and the Roland Sutton Academic Trust (RSAT).Peer reviewedPublisher PD

Political Intervention in a National Tourism Event: The Politics of Homecoming Scotland

The aim of this paper is to provide insight and analysis into the politics of a government tourism initiative within the geographic context of Scotland. It highlights the catalytic role of key government agencies in channelling investment, energies, events and marketing effort into a nationally focused tourism theme: Homecoming Scotland 2009 (HS09). The paper delves below the public relations veneer of many such activities to uncover the political debates and controversies that may have detracted from the successes of the initiative.div_BaMAudit Scotland. (2010). The Gathering 2009, project brief. Eirich, F., & McLaren, J. (2008). Engaging the Scottish diaspora. Edinburgh: The Scottish Government's Europe, External Affairs and Cultural Analytical Unit. Hall, C. M. (2005). Contemporary issues in tourism management. In L. Pender and R. Sharpley (Eds.), The Management of Tourism (pp. 217-245). London: Sage. Hutcheon, P. (2009, October 18). Probe call as public carries burden for losses by clan gathering firm, Sunday Herald. Kemp, K. (2009, October). What has Scotland done to its brand? Business Herald, pp. 8-9. Lederer, P. (2009, October). Homecoming Scotland: the making of Scotland. Edinburgh: Edinburgh City Council. McCracken, E. (2008, May 31). Poetic injustice: fear that Robert Burns has been sidelined in celebrations for his own 250th birthday. The Herald. Morrison, A., & Hay, B. (2010). A review of homecoming Scotland. Fraser of Allander Economic Commentary, 34(1), 44-54. Page, S., & Connell, J. (2006). Tourism: a modern synthesis. London: Thomson Learning. Ryan, C. (2005). Destination marketing and technology. In L. Pender and R. Sharpley (Eds.), The Management of Tourism (pp. 246-258). London: Sage. Scottish Government (2007a). Join a year-long celebration of Scotland and the Scots. (News Release). Scottish Government (2007b). Launch of M events fund to encourage Scots to come home. (News Release). Scottish Government (2009). Homecoming - the real thing. (News Release).pub2673pu

Subcellular fractionation of primary chronic lymphocytic leukemia cells to monitor nuclear/ cytoplasmic protein trafficking

Nuclear export of macromolecules is often deregulated in cancer cells. Tumor suppressor proteins, such as p53, can be rendered inactive due to aberrant cellular localization disrupting their mechanism of action. The survival of chronic lymphocytic leukaemia (CLL) cells, among other cancer cells, is assisted by the deregulation of nuclear to cytoplasmic shuttling, at least in part through deregulation of the transport receptor XPO1 and the constitutive activation of PI3K-mediated signaling pathways. It is essential to understand the role of individual proteins in the context of their intracellular location to gain a deeper understanding of the role of such proteins in the pathobiology of the disease. Furthermore, identifying processes that underlie cell stimulation and the mechanism of action of specific pharmacological inhibitors, in the context of subcellular protein trafficking, will provide a more comprehensive understanding of the mechanism of action. The protocol described here enables the optimization and subsequent efficient generation of nuclear and cytoplasmic fractions from primary chronic lymphocytic leukemia cells. These fractions can be used to determine changes in protein trafficking between the nuclear and cytoplasmic fractions upon cell stimulation and drug treatment. The data can be quantified and presented in parallel with immunofluorescent images, thus providing robust and quantifiable data

Stakeholder and parent co-production within an NHS-tailored evidence synthesis of breastfeeding support in the UK:the Action4Breastfeeding project

BackgroundCo-production in research enhances the quality and relevance of research findings. Stakeholder engagement was integral to the Action4Breastfeeding project. Our approach to stakeholder and parent involvement was ‘active involvement’ (Pollock et al 2018) throughout the process of evidence synthesis including planning, production and dissemination.MethodsEngagement was achieved through a stakeholder working group and a parents’ panel, supplemented by focus group discussions with women from groups least likely to breastfeed. All four UK countries were represented. The stakeholder working group included members of third sector organisations, policymakers, NHS practitioners, and commissioners. The parents’ panel included women who had breastfed a child within the last three years and fathers. Focus group participants were recruited by a peer support organisation working with disadvantaged families. The three groups met separately four times during the study. Co-production activities included: a) discussing priorities for breastfeeding support, b) agreeing criteria to assess transferability of effective interventions from global evidence to the UK setting; c) identifying barriers to implementing breastfeeding support in NHS settings, and d) developing and prioritising strategies to overcome the identified barriers. The online meetings were supplemented with a modified Delphi survey. Focus groups were held online and in-person. Members of the stakeholder working group and parents panel attended in-person workshops held around the UK as the final stage of the project. A project extension for women with multiple long-term conditions mirrored this work.Results/findingsPractical elements of engaging stakeholders and parents in co-creation within an evidence synthesis will be presented, including achieving trust, confidentiality, and good working relations, valuing contributions and maintaining engagement. Examples of diversity and differing priorities within the various stages of the evidence synthesis will be provided. Ways of managing these to produce an NHS-tailored implementation and evaluation strategy framework will be discussed. We plan to continue engagement beyond the funded project to ensure effective knowledge mobilisation (Grindall et al 2022)ConclusionCo-creation was essential to this evidence synthesis and whilst not always easy to achieve, resulted in rich discussions and diverse priorities that will contribute to the development of cost-effective breastfeeding support interventions in the UK

mTORC1 activity is essential for erythropoiesis and B cell lineage commitment

Mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that mediates phosphoinositide-3-kinase (PI3K)/AKT signalling. This pathway is involved in a plethora of cellular functions including protein and lipid synthesis, cell migration, cell proliferation and apoptosis. In this study, we proposed to delineate the role of mTORC1 in haemopoietic lineage commitment using knock out (KO) mouse and cell line models. Mx1-cre and Vav-cre expression systems were used to specifically target Raptorfl/fl (mTORC1), either in all tissues upon poly(I:C) inoculation, or specifically in haemopoietic stem cells, respectively. Assessment of the role of mTORC1 during the early stages of development in Vav-cre+Raptorfl/fl mice, revealed that these mice do not survive post birth due to aberrations in erythropoiesis resulting from an arrest in development at the megakaryocyte-erythrocyte progenitor stage. Furthermore, Raptor-deficient mice exhibited a block in B cell lineage commitment. The essential role of Raptor (mTORC1) in erythrocyte and B lineage commitment was confirmed in adult Mx1-cre+Raptorfl/fl mice upon cre-recombinase induction. These studies were supported by results showing that the expression of key lineage commitment regulators, GATA1, GATA2 and PAX5 were dysregulated in the absence of mTORC1-mediated signals. The regulatory role of mTOR during erythropoiesis was confirmed in vitro by demonstrating a reduction of K562 cell differentiation towards RBCs in the presence of established mTOR inhibitors. While mTORC1 plays a fundamental role in promoting RBC development, we showed that mTORC2 has an opposing role, as Rictor-deficient progenitor cells exhibited an elevation in RBC colony formation ex vivo. Collectively, our data demonstrate a critical role played by mTORC1 in regulating the haemopoietic cell lineage commitment

Effectiveness and cost-effectiveness of basic versus biofeedback-mediated intensive pelvic floor muscle training for female stress or mixed urinary incontinence: protocol for the OPAL randomised trial

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordIntroduction Accidental urine leakage is a distressing problem that affects around one in three women. The main types of urinary incontinence (UI) are stress, urgency and mixed, with stress being most common. Current UK guidelines recommend that women with UI are offered at least 3 months of pelvic floor muscle training (PFMT). There is evidence that PFMT is effective in treating UI, however it is not clear how intensively women have to exercise to give the maximum sustained improvement in symptoms, and how we enable women to achieve this. Biofeedback is an adjunct to PFMT that may help women exercise more intensively for longer, and thus may improve continence outcomes when compared with PFMT alone. A Cochrane review was inconclusive about the benefit of biofeedback, indicating the need for further evidence. Methods and analysis This multicentre randomised controlled trial will compare the effectiveness and cost-effectiveness of PFMT versus biofeedback-mediated PFMT for women with stress UI or mixed UI. The primary outcome is UI severity at 24 months after randomisation. The primary economic outcome measure is incremental cost per quality-adjusted life-year at 24 months. Six hundred women from UK community, outpatient and primary care settings will be randomised and followed up via questionnaires, diaries and pelvic floor assessment. All participants are offered six PFMT appointments over 16 weeks. The use of clinic and home biofeedback is added to PFMT for participants in the biofeedback group. Group allocation could not be masked from participants and healthcare staff. An intention-to-treat analysis of the primary outcome will estimate the mean difference between the trial groups at 24 months using a general linear mixed model adjusting for minimisation covariates and other important prognostic covariates, including the baseline score. Ethics and dissemination Approval granted by the West of Scotland Research Ethics Committee 4 (16/LO/0990). Written informed consent will be obtained from participants by the local research team. Serious adverse events will be reported to the data monitoring and ethics committee, the ethics committee and trial centres as required. A Standard Protocol Items: Recommendations for Interventional Trials checklist and figure are available for this protocol. The results will be published in international journals and included in the relevant Cochrane review. Trial registration number ISRCTN57746448; Pre-results.National Institute for Health Research (NIHR

From theory to practice : a roadmap for applying dual-process theory in design cognition research

Dual-process theory categorises cognition into two types of processing: Type 1 which is intuitive, autonomous processing, and Type 2 which is reflective processing that burdens limited executive cognitive resources (i.e. working memory). A recent call for increased theory-driven research in the field of design has led to a framing of dual-process theory as a foundation for design research. This research note presents a roadmap for future dual-process theory-driven design research outlining three main stages: defining dual-process theory constructs, determining research focus, and selecting research methods. Across these stages, we offer a conceptualisation of dual-process theory for design researchers, outlining the main concepts of the theory. We then present how a research study design must consider the nature of design problems (complex, ill-structured, ambiguous), designers, and the practice of design. Finally, we outline the main methods employed in dual-process theory research: behavioural, physiological, and self-report measures, suggesting ways to adapt such methods to design contexts. Ultimately, this work presents how dual-process theory may connect with theories of cognition often considered in design and offers a path forward for dual-process theory-driven design research

The discrete roles of individual FOXO transcription factor family members in B-cell malignancies

Forkhead box (FOX) class O (FOXO) proteins are a dynamic family of transcription factors composed of four family members: FOXO1, FOXO3, FOXO4 and FOXO6. As context-dependent transcriptional activators and repressors, the FOXO family regulates diverse cellular processes including cell cycle arrest, apoptosis, metabolism, longevity and cell fate determination. A central pathway responsible for negative regulation of FOXO activity is the phosphatidylinositol-3-kinase (PI3K)-AKT signalling pathway, enabling cell survival and proliferation. FOXO family members can be further regulated by distinct kinases, both positively (e.g., JNK, AMPK) and negatively (e.g., ERK-MAPK, CDK2), with additional post-translational modifications further impacting on FOXO activity. Evidence has suggested that FOXOs behave as ‘bona fide’ tumour suppressors, through transcriptional programmes regulating several cellular behaviours including cell cycle arrest and apoptosis. However, an alternative paradigm has emerged which indicates that FOXOs operate as mediators of cellular homeostasis and/or resistance in both ‘normal’ and pathophysiological scenarios. Distinct FOXO family members fulfil discrete roles during normal B cell maturation and function, and it is now clear that FOXOs are aberrantly expressed and mutated in discrete B-cell malignancies. While active FOXO function is generally associated with disease suppression in chronic lymphocytic leukemia for example, FOXO expression is associated with disease progression in diffuse large B cell lymphoma, an observation also seen in other cancers. The opposing functions of the FOXO family drives the debate about the circumstances in which FOXOs favour or hinder disease progression, and whether targeting FOXO-mediated processes would be effective in the treatment of B-cell malignancies. Here, we discuss the disparate roles of FOXO family members in B lineage cells, the regulatory events that influence FOXO function focusing mainly on post-translational modifications, and consider the potential for future development of therapies that target FOXO activity