233 research outputs found

    WNK1-dependent osmoregulation in CD4⁺ T cell activation

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    CD4+ T cell activation is critical for the initiation of the adaptive immune response. In particular, through the provision of help to B cells, CD4+ T cells are essential for the generation of high-affinity, class-switched antibodies specific for epitopes on invading pathogens. CD4+ T cells also augment the activation of CD8+ cytotoxic T lymphocytes and modulate the effector function of innate immune cells. These features of the immune response are essential for the clearance of many pathogens and are conditional on the ability of a small population of antigen-specific CD4+ T cells to rapidly expand in response to antigenic challenge. In this study we show that this expansion is strongly dependent on the activity of the WNK1 kinase, and that in the absence of WNK1, CD4+ T cells are unable to support a class-switched antibody response. WNK1 has been extensively studied in the distal nephron of the kidney, where it regulates ion transport, and consequently blood pressure, via the STK39 and OXSR1 kinases and the SLC12A-family of ion co-transporters. Here we show that this osmoregulatory function of WNK1 is required for TCR signalling in CD4+ T cells and the subsequent entry of these cells into G1 phase of the cell cycle. Furthermore, having entered the cell cycle, WNK1-deficient T cells show a reduced rate of DNA replication and activate the ATR-mediated cell cycle checkpoint, resulting in a G2/M blockade. CD4+ T cells carrying mutations in both Oxsr1 and Stk39 phenocopy WNK1-deficient T cells, although the defects in TCR-induced proliferation are less severe. Taken together, these data suggest that WNK1 regulates cell cycle progression via the OXSR1 and STK39 signalling pathways, as well as via another, non-canonical pathway. Importantly, the defective TCR signalling and G1 entry exhibited by WNK1-deficient CD4+ T cells can be rescued by activating the cells in hypotonic medium. These novel findings reveal fundamental roles for WNK1 activity and transmembrane water movement in antigen receptor signalling and cell cycle dynamics

    Viral infection identifies micropeptides differentially regulated in smORF-containing lncRNAs

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    Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, studies utilizing next-generation sequencing technologies show that a subset of the >10,000 lncRNAs in the mammalian genome contain small open reading frames (smORFs) associated with active translation, i.e., many lncRNAs are not noncoding. Here, we use genome-wide high-throughput methods to identify potential micropeptides in smORF-containing lncRNAs involved in the immune response. Using influenza as a viral infection model, we performed RNA-seq and ribosome profiling to track expression and translation of putative lncRNAs that may encode for peptides and identify tens of potential candidates. Interestingly, many of these peptides are highly conserved at the protein level, strongly suggesting biological relevance and activity. By perusing publicly available data sets, four potential peptides of interest seem common to stress induction and/or are highly conserved; potential peptides from the MMP24-AS1, ZFAS1, RP11-622K12.1, and MIR22HG genes. Interestingly, using an antibody against the potential peptide encoded by MIR22HG RNA, we show that the peptide is stably expressed in the absence of infection, and upregulated in response to infection, corroborating the prediction of the ribosome profiling results. These data show the utility of perturbation approaches in identifying potentially relevant novel molecules encoded in the genome

    The Allied Health Professional Workforce: Evidence and Impact

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    Health workforce issues have been on the top of the policy agenda across the globe in recent years. Any dialogue with health policy makers about the health workforce is likely to engender the following key questions: - How do we plan how many health workers to educate, and employ? - How can we improve recruitment, retention and return? - Which incentives are effective in motivating staff? - How can we determine and deploy the most effective skill mix of staff? - How do we improve productivity? These health workforce challenges were summarised by WHO in the 2006 World Health Report, which presented an estimate that there was a world-wide shortage of almost 4.3 million health care workers, and that 57 countries, mostly in sub-Saharan Africa, had critical shortages. Sub-Saharan Africa had only 4% of health workers but 25% of the global burden of disease (GBD); in contrast the Americas had 37% of health workers but only 10% of GBD (WHR 2006). One critical dimension of shortages- is that there is uneven distribution of health workers to meet demand, by country, by region, by sector and by occupational mix. Against this backdrop of global shortages, and in the context of cost containment measures in many countries, developed and developing, it is critical that the allied health professional (AHP) workforce receives sufficient policy attention to enable it to make an optimal contribution to meeting health needs. At the moment, this is not happening fully in many countries and contexts. In part this is because the AHP workforce is often a newer element in the health system, and may not have developed the policy influencing mechanisms that are used by more established- and larger in number professions such as medicine and nursing. In part it can also be because some policy makers do not understand fully just what a contribution is being made, and could be made, by the AHP workforce. This paper summarises the recent evidence base on the contribution of the AHP workforce to health service delivery, and highlights current AHP workforce priorities.sch_nurunpub4303unpu

    International recruitment of physiotherapists: a report for the Chartered Society for Physiotherapy.

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    MY Voice: A participatory action research project with men, women and young people on female genital mutilation (FGM) in Scotland

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    MY Voice is an innovative participatory action research project with affected communities on Female Genital Mutilation (FGM) in Scotland. The project aims are to facilitate community engagement on FGM with women, men, young people and religious leaders, to enable their voices to be heard, and to contribute to the development of awareness-raising around FGM, as well as ensuring culturally appropriate services for Scotland. There have been multiple calls for greater community participation and leadership in the work on FGM in Scotland from those directly affected (see section 1.3). The findings from MY Voice can start to identify key issues and help determine ways in which community participation can be built in to the Scottish response to FGM more effectively.Funding was provided by the Scottish Government Violence Against Women Fund.https://www.waverleycare.orgpubpu

    Retirement patterns of doctors

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    Edinburghsch_nurpub764pu

    Reference to the index of Harry O'May's scrapbook of the 1930's.

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    Press cuttings relating to the O'May and other Derwent ferry services, Tasmanian shipping and history (1930's), also pay sheet of Rosny Estate & Ferry Co. Ltd (18-28 June 1925)

    Safe staffing levels - a national imperative. The UK nursing Labour Market Review 2013

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    LondonThis report is the 2013 annual review of the UK nursing labour market commissioned by the Royal College of Nursing. Events over the last twelve months point to the urgent need to address both the national security of the supply of nurses, and the local ability to determine evidence-based nurse staffing levels.div_PaSThe Mid Staffordshire NHS Foundation Trust Public Inquiry (2013) Report of the Mid Staffordshire NHS Foundation Trust Public Inquiry: executive summary. London: Stationery Office (Chair: R Francis). www.midstaffspublicinquiry.com/sites/default/files/report/Executive%20summary.pdf 2 Royal College of Nursing (2013) Mid Staffordshire NHS Foundation Trust Public Inquiry Report: Response of the Royal College of Nursing. RCN, London http://www.rcn.org.uk/__data/assets/pdf_file/0010/530956/004476.pdf 3 See e.g. Healthcare Improvement Scotland (2013) Announced Inspection Report - care for older people in acute hospitals, Aberdeen Royal Infirmary, NHS Grampian. Healthcare Improvement Scotland, Edinburgh www.healthcareimprovementscotland.org/our_work/inspecting_and_regulating_care/opah_grampian/aberde en_royal_infirmary_jun13.aspx 4 Scottish Government (2012) News Releases. Nurse staffing levels. 26th November. Scottish Government, Edinburgh. http://www.scotland.gov.uk/News/Releases/2012/11/staff261112 5 Buckland L (2013) 67 million boost to NHS staff to avert age crisis. Scotland on Sunday, August 11, p6. 6 Royal College of Nursing, Wales (2013) RCN in Wales responds to Health Minister's 10 million nurse recruitment announcement. www.rcn.org.uk/newsevents/news/article/wales/rcn_in_wales_responds_to_health_ministers_10_million_nu rse_recruitment_funding 7 DHSSPS (2013) Health Minister and RCN agree on nursing priorities for Workforce Plans. www.northernireland.gov.uk/news-dhssps-080713-health-minister-and 8 Department of Health (2013) The Cavendish Review. Review of healthcare assistants and support workers in NHS and social care. Department of Health, London. www.gov.uk/government/uploads/system/uploads/attachment_data/file/212732/Cavendish_Review_ACCESS IBLE_-_FINAL_VERSION_16-7-13.pdf 9 NHS England (2013) Review into the quality of care and treatment provided by 14 hospital trusts in England: overview report. NHS England, London. www.nhs.uk/NHSEngland/bruce-keogh-review/Documents/outcomes/keogh-review-final-report.pdf 10 National Advisory Group on the Safety of Patients in England (2013) A promise to learn- a commitment to act: Improving the Safety of Patients in England. NHS England, London www.gov.uk/government/uploads/system/uploads/attachment_data/file/226703/Berwick_Report.pdf 11 Imison C, Bohmer R (2013) NHS and social care workforce: Meeting our needs now and in the future? King's Fund, London www.kingsfund.org.uk/sites/files/kf/field/field_publication_file/perspectives-nhs-social-care-workforcejul13. pdf 12 Centre for Workforce Intelligence (2013) Future nursing workforce projections - starting the discussion, London: CfWI. www.cfwi.org.uk/publications/future-nursing-workforce-projectionsstarting% 20the%20discussion 13 Buchan J Seccombe I (2011) A decisive decade. The 2011 UK nursing labour market review. Royal College of Nursing, London. www.rcn.org.uk/__data/assets/pdf_file/0006/405483/LMR2011_FINAL.pdf 14 RCN Scotland (2013) Student numbers maintained, but looming shortage of nurses, warns RCN. RCN Edinburgh, 25 February. www.rcn.org.uk/newsevents/news/article/scotland/student_numbers_maintained,_but_looming_shortage_of _nurses,_warns_rcn 15 Department of Health (2013) Delivering high quality, effective, compassionate care: Developing the right people with the right skills and the right values. A mandate from the Government to Health Education England: April 2013 to March 2015. Department of Health, London http://hee.nhs.uk/wp-content/blogs.dir/321/files/2013/05/29257_2900971_Delivering_Accessible.pdf 16 National Audit Office (2013). Managing the transition to the reformed health system. NAO, London. www.nao.org.uk/report/managing-the-transition-to-the-reformed-health-system/ 17 Timmins N (2013) The four UK health systems: Learning from each other. King's Fund, London www.kingsfund.org.uk/sites/files/kf/field/field_publication_summary/four-uk-health-systems-jun13.pdf 18 Audit Scotland (2012) NHS financial performance 2011/12. Audit Scotland, Edinburgh www.audit-scotland.gov.uk/docs/health/2012/nr_121025_nhs_finances.pdf 19 National Audit Office (2012) Progress in making NHS efficiency savings. NAO London. 34 www.nao.org.uk/report/progress-in-making-nhs-efficiency-savings/ 20 Jones N, Charlesworth A (2013) The anatomy of health spending 2011/12. Nuffield Trust, London. www.nuffieldtrust.org.uk/publications/anatomy-health-spending-201112-review-nhs-expenditure-and-labourproductivity 21 Roberts A, Marshall L, Charlesworth A (2012) A decade of austerity? Nuffield Trust, London www.nuffieldtrust.org.uk/sites/files/nuffield/121203_a_decade_of_austerity_full_report_1.pdf 22 Duffin C (2013) Stop start recruitment of nurses is damaging morale and patient care. Nursing Standard 27(48) p5 23 Department of Health (2013) National health visitor plan: progress and future implementation. DH London. www.gov.uk/government/publications/health-visitor-vision 24 NHS Employers (2013) NHS Staff Council. NHS Working Longer Review: Audit of existing research. NHS Staff Council/ University of Bath 25 Nursing Times News (2013) Retirement age health visitors offered sweeteners to stay in work. Nursing Times 27 (44), July 3 26 Sprinks J (2013) Minister tells trusts to cut spending on agency staff and equipment. Nursing Standard 27 (50), p10. 27 UCAS annual datasets (subject dataset v2.0, JACS3 subject line B7 Nursing) 28 NHS Education for Scotland, 2011, Untangling a complex issue: Nursing & Midwifery Student Recruitment and Retention Delivery Group Annual report 2010-11 www.nes.scot.nhs.uk/media/536359/delivery_group_-_annual_report_2010-11_final.pdf 29 Nursing Times, 27 September 2011, Huge fall in numbers dropping out of nursing courses 30 http://hee.nhs.uk/2013/05/09/top-nurses-to-oversee-pilots-on-pre-degree-care-experience/ 31 Centre for Workforce Intelligence (2013) Horizon scanning - A strategic review of the future healthcare workforce: Informing the nursing workforce www.cfwi.org.uk/publications/horizon-scanning-a-strategic-review-of-the-future-healthcare-workforceinforming- the-nursing-workforce 32 Queens Nursing Institute (2013) District Nurse Education 2012/13. QNI London www.qni.org.uk/campaigns/report_on_district_nurse_education 33 RCN Policy Unit (2012) The Community Nursing Workforce in England. RCN, London 34 Department of Health (2013) Care in local communities - district nurse vision and model. DH London. www.gov.uk/government/uploads/system/uploads/attachment_data/file/213363/vision-district-nursing- 04012013.pdf 35 Nursing Times (2013) Retirement age health visitors offered sweeteners to stay in work. Nursing Times, 27 (44) July 3rd. 36 http://frontlinefirst.rcn.org.uk/sites/frontlinefirst/index.php/blog/entry/scotlands-families-deserve-healthvisitors 37 Sprinks J (2013) Drafting in of Danish health visitors is just a short term fix, says Unison. Nursing Standard 27 (51), p9 38 House of Commons, Health Committee (2007) Workforce Planning: Fourth Report of Session 2006-07 Volume I Report, together with formal minutes. Health Committee, London: The Stationery Office Limited www.publications.parliament.uk/pa/cm200607/cmselect/cmhealth/171/171i.pdf R C N L A B O U R M A R K E T R E V I E W The RCN represents nurses and nursing, promotes excellence in practice and shapes health policies September 2013 RCN Online www.rcn.org.uk RCN Direct www.rcn.org.uk/direct 0345 772 6100 Published bypub3274pu

    Exploring the impact of sport participation in the Homeless World Cup on individuals with substance abuse or mental health disorders

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    Objective To explore the role of the relationship between sport and social capital in negotiating improved social outcomes for homeless individuals with mental illness and/or substance abuse issues. Method A qualitative analysis of semi-structured interviews with 27 participants of the Melbourne 2008 Homeless World Cup (eight from Scotland and 19 from Australia). Interview questions focussed on the participants' interest of and participation in sport; factors influencing participation; any changes perceived by the individuals as a result of program participation; and in order to identify changes pre and post event, any current experiences of social exclusion. Results The role of social capital in mental health and substance abuse outcomes is addressed by the authors, in addition to the contribution of sport to the building of social capital. Conclusion Findings suggest that sport initially provided social bonding within a limited social network, yet over time other types of social capital (bridging and linking) were exhibited by participants, and enabled access to ancillary services provided by the program that led to reductions or cessation of both substance abuse and symptoms of mental illness. Implications Sport can provide an effective vehicle for the accrual of social capital, which may positively impact the mental health and substance abuse patterns of participants from marginalised and at-risk communities.sch_nur1.Dunn S. Creating accepting communities: report of the MIND inquiry into social exclusion and mental health problems. London: Mind1999. 2.Department of Health. Making it happen: a guide to delivering mental health promotion. London: Department of Health2001. 3.Mental Health Foundation. Strategies for living. London: MHF2000. 4.Hawkins R, Abrams C. 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