Clustering in surgical trials : database of intracluster correlations

PMID: 22217216 [PubMed - indexed for MEDLINE] PMCID: PMC3311136 Free PMC ArticlePeer reviewedPublisher PD

The role of FOXP3 in autoimmunity

FOXP3 controls the development and function of T regulatory cells (Tregs). Autoimmunity is linked to changes in FOXP3 activity that can occur at multiple levels and lead to Treg dysfunction. For example, changes in IL-2 signaling, FOXP3 transcription and/or post-translational modifications can all contribute to loss of self-tolerance. As additional pathways of FOXP3 regulation are elucidated, new therapeutic approaches to increase Treg activity either by cell therapy or pharmacological intervention are being tested. Early success from pioneering studies of Treg-based therapy in transplantation has promoted the undertaking of similar studies in autoimmunity, with emerging evidence for the effectiveness of these approaches, particularly in the context of type 1 diabetes

Experience of sexual self-esteem among men living with HIV

Much of the focus on sexual health for people living with HIV has been on promoting safe sex behaviours. However, also important for sexual health is a positive sexual self-esteem. This article reports on an interpretative phenomenological analysis of interviews with seven men about the impact that having HIV has had on their sense of sexual self. Five overarching themes were identified: the ‘destruction’ of a sexual self; feeling sexually hazardous; sexual inhibition; reclaiming a sexual self and finding a place through sero-sorting. With HIV now being a chronic illness, interventions are required to support people to lead sexually satisfying lives

Can Computer-Assisted Training of Prerequisite Motor Skills Help Enable Communication in People with Autism?

Our and others' research indicates that in fully a third of people with autism who lack communicative speech, the communication deficit may actually be a deficit in motor skills necessary to move the mouth and the vocal tract. These individuals have difficulties in fine, gross and especially oral motor skills, and a disparity between impaired expressive language and relatively intact receptive language: that is to say, they can listen but not speak. Because involvement in research and receipt of the fullest educational, occupational and other services demands ability to interact verbally and to control one's movements and actions, these people get the short end of the stick when it comes to scientific enquiry and pedagogic and therapeutic practice. Point OutWords, tablet-based software designed in collaboration with autistic clients and their communication therapists, exploits the autistic fascination with parts and details to motivate attention to learning manual motor and oral motor skills essential for communication. Along the way, autistic clients practise pointing and dragging at objects, then pointing at sequences of letters on a keyboard, and even speaking the syllables represented by these letters. Whereas many teaching and learning strategies adapted from methods for non-autistic people end up working against autistic cognition by asking people with autism to do what they cannot easily do, Point OutWords works with autistic cognition, by beginning from the autistic skill at manipulating parts and details. Users and their parents or guardians can opt into collection of data on motor interactions with Point OutWords; these internal measures of motor skills development are complemented by external, standardised tests of motor, oral motor and communicative development. These quantitative measures are collected alongside reports on Point OutWords's acceptability to users, and users' fidelity to a recommended treatment regime, so as to evaluate feasibility of a larger randomised controlled trial

Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations

There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

Estimation of greenhouse gas emissions from spontaneous combustion/fire of coal in opencast mines – Indian context

There are a significant number of uncontrolled coal mine fires (primarily due to spontaneous combustion of coal), which are currently burning all over the world. These spontaneous combustion sources emit greenhouse gases (GHGs). A critical review reveals that there are no standard measurement methods to estimate GHG emissions from mine fire/spontaneous combustion areas. The objective of this research paper was to estimate GHGs emissions from spontaneous combustion of coals in the Indian context. A sampling chamber (SC) method was successfully used to assess emissions at two locations of the Enna Opencast Project (OCP), Jharia Coalfield (JCF), for 3 months. The study reveals that measured cumulative average emission rate for CO2 varies from 75.02 to 286.03 gs−1m−1 and CH4 varies from 41.49 to 40.34 gs−1m−1 for low- and medium-temperature zones. The total GHG emissions predicted from this single fire affecting mines of JCF vary from 16.86 to 20.19 Mtyr−

Total versus partial knee replacement in patients with medial compartment knee osteoarthritis : the TOPKAT RCT

Article history The research reported in this issue of the journal was funded by the HTA programme as project number 08/14/08. The contractual start date was in January 2010. The draft report began editorial review in February 2019 and was accepted for publication in October 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements TOPKAT study group Chief investigator David Beard. Trial co-investigators Nigel Arden (Oxford), Helen Campbell (Oxford), Marion Campbell (Aberdeen), Andrew Carr (Oxford), Jonathan Cook (Aberdeen then Oxford), Helen Doll (Oxford), Ray Fitzpatrick (Oxford), David Murray (Oxford) and Andrew Price (Oxford). Trial management Mayret Castillo (until 2011), Cushla Cooper, Loretta Davies, Anne Duncan (until 2017), Gordon Fernie, Sophie Halpin (until 2015) and Alison McDonald. Trial administration Katie Chegwin, Jiyang Li (until 2018), Elena Rabaiotti (until 2013), Sandra Regan (until 2012) and Victoria Stalker (until 2014). Data management Diana Collins (until 2013), Janice Cruden, Akiko Greshon, Kay Holland and Beverley Smith (until 2017). Database/programming management Gladys McPherson. Trial statisticians Charles Boachie (until 2013), Jemma Hudson and Graeme MacLennan. Health economists Helen Campbell (until 2015), Francesco Fusco (until 2018), Seamus Kent and Jose Leal. We would also like to thank Hannah Wilson (DPhil student, University of Oxford) for her help with the update to the literature search. Research teams We are grateful to the participants and research teams at collaborating hospital sites: Aneurin Bevan University Health Board, Royal Gwent Hospital Ruth Jenkins, Mark Lewis [principal investigator (PI)] and Witek Mintowt-Czyz. Belfast Health and Social Care Trust, Musgrove Park Hospital, Belfast David Beverland (PI), Leeann Bryce, Julie Catney, Ian Dobie, Emer Doran and Seamus O’Brien. Chesterfield Royal Hospital NHS Foundation Trust Fazal Ali, Heather Cripps, Amanda Whileman, Phil Williams (PI) and Julie Toms. County Durham and Darlington NHS Foundation Trust Ellen Brown, Gillian Horner, Andrew Jennings (PI) and Glynis Rose. East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital Frances Bamford, Wendy Goddard, Hans Marynissen (PI), Haleh Peel and Lyndsey Richards. Great Western Hospitals NHS Foundation Trust, Swindon Amanda Bell, Sunny Deo, Sarah Grayland, David Hollinghurst, Suzannah Pegler, Venkat Satish (PI) and Claire Woodruffe. Harrogate and District NHS Foundation Trust, Harrogate Nick London (PI), David Duffy, Caroline Bennett and James Featherstone. Hull and East Yorkshire Hospitals NHS Trust Joss Cook, Kim Dearnley, Nagarajan Muthukumar (PI), Laura Onuoha and Sarah Wilson. Maidstone and Tunbridge Wells NHS Trust, Medway Sandhu Banher, Eunice Emeakaroha, Jamie Horohan, Sunil Jain (PI) and Susan Thompson. Mid Yorkshire Hospitals NHS Trust Sarah Buckley, Aaron Ng (PI), Ajit Shetty and Karen Simeson. Milton Keynes University Hospital NHS Foundation Trust Julian Flynn, Meryl Newsom, Cheryl Padilla-Harris and Oliver Pearce (PI). NHS Grampian, Woodend Hospital, Aberdeen James Bidwell (PI), Alison Innes, Winifred Culley and Bill Ledingham and Janis Stephen. North Bristol NHS Trust Rachel Bray, Hywel Davies, Debbie Delgado, Jonathan Eldridge, Leigh Morrison, James Murray (PI), Andrew Porteous and James Robinson. North Cumbria University Hospitals NHS Trust, Carlisle Matt Dawson (PI), Raj Dharmarajan, David Elson, Will Hage, Nicci Kelsall and Mike Orr. North Tees and Hartlepool NHS Foundation Trust, Stockton-On-Tees Jackie Grosvenor, SS Maheswaran (PI), Claire McCue, Hemanth Venkatesh, Michelle Wild and Deborah Wilson. Oxford University Hospitals NHS Trust, Nuffield Orthopaedic Centre Chris Dodd, William Jackson (PI), Pam Lovegrove, David Murray, Jennifer Piper and Andrew Price. Royal United Hospitals Bath NHS Foundation Trust, Bath Neil Bradbury, Lucy Clark, Stefanie Duncan, Genevieve Simpson and Allister Trezies (PI). Sherwood Forest Hospitals NHS Foundation Trust, Kings Mill Hospital, Sutton in Ashfield Vikram Desai (PI), Cheryl Heeley, Kramer Guy and Rosalyn Jackson. South Devon Healthcare NHS Foundation Trust, Torbay Alan Hall, Gordon Higgins (PI), Michael Hockings, David Isaac and Pauline Mercer. Stockport NHS Foundation Trust, Stockport Lindsey Barber, Helen Cochrane, Janette Curtis, Julie Grindey, David Johnson (PI), and Phil Turner. The Hillingdon Hospitals NHS Trust David Houlihan-Burne (PI), Briony Hill, Ron Langstaff and Mariam Nasseri. The Ipswich Hospital NHS Trust, Ipswich Mark Bowditch, Chris Martin, Steven Pryke, Bally Purewal, Chris Servant (PI), Sheeba Suresh and Claire Tricker. University Hospitals of Leicester NHS Trust, Leicester Robert Ashford, Manjit Attwal, Jeanette Bunga, Urjit Chatterji, Susan Cockburn, Colin Esler (PI), Steven Godsiff, Tim Green, Christina Haines and Subash Tandon. University Hospitals of North Midlands NHS Trust, Stoke on Trent Racquel Carpio, Sarah Griffiths, Natalie Grocott and Ian dos Remedios (PI). University Hospital Southampton NHS Foundation Trust David Barrett, Phil Chapman-Sheath, Caroline Grabau, Jane Moghul, William Tice (PI) and Catherine Trevithick. United Lincolnshire Hospitals NHS Trust, Boston Rajiv Deshmukh, Mandy Howes, Kimberley Netherton, Dipak Raj (PI) and Nikki Travis. United Lincolnshire Hospitals NHS Trust, Lincoln Mohammad Maqsood, Rebecca Norton, Farzana Rashid, Alison Raynor, Mark Rowsell and Karen Warner. We would like to thank the external members of the TSC and DMC for their advice and support for the project. Trial Steering Committee Donna Dodwell as our patient representative, Simon Donell (chairperson) (University of East Anglia), Shawn Tavares (Royal Berkshire Hospital) and Jonathan Waite (South Warwickshire NHS Foundation Trust). Data Monitoring Committee Karen Barker (Oxford University Hospitals NHS Foundation Trust), Gordon Murray (chairperson) (University of Edinburgh) and Hamish Simpson (University of Edinburgh). Independent review and interpretation of results Professor David Torgerson (University of York). Professor Chris Maher (University of Sydney). Mr Peter Brownson (The Royal Liverpool and Broadgreen University Hospitals NHS Trust). Professor Simon Donell (University of East Anglia, Norwich). Mr Mark Mullins (Abertawe Bro Morgannwg University Health Board). Professor Jane Blazeby (Bristol University).Peer reviewedPublisher PD