8 research outputs found
The professional development of human service professionals in rural and remotes areas: Investigating the affordances of the internet
No full textThis paper is a report of work-in-progress on a project that seeks to identify effective ways in which the Internet can be used to overcome the isolation of human service professionals employed in rural and remote areas. Professionals employed in rural locations in Australia will be surveyed and interviewed with regard to their needs, awareness, use and benefits of the Internet for professional development and support. Guidelines will be produced to document strategies for the design and delivery of effective use of the Internet to support and assist professionals in rural and remote areas
Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx
No full textCorrection to: Nature https://doi.org/10.1038/s41586-023-05783-5 Published online 12 April 2023.
In the version of the article initially published, the symbols for death (x) and censored (>) were swapped in the graphs in Fig. 1. The figure has now been corrected in the HTML and PDF versions of the article
Video-assisted thoracoscopic surgery lobectomy at 20 years: A consensus statement
No full textOBJECTIVE: Video-assisted thoracoscopic surgery (VATS) lobectomy has been gradually accepted as an alternative surgical approach to open thoracotomy for selected patients with non-small-cell lung cancer (NSCLC) over the past 20 years. The aim of this project was to standardize the perioperative management of VATS lobectomy patients through expert consensus and to provide insightful guidance to clinical practice. METHODS: A panel of 55 experts on VATS lobectomy was identified by the Scientific Secretariat and the International Scientific Committee of the '20th Anniversary of VATS Lobectomy Conference-The Consensus Meeting'. The Delphi methodology consisting of two rounds of voting was implemented to facilitate the development of consensus. Results from the second-round voting formed the basis of the current Consensus Statement. Consensus was defined a priori as more than 50% agreement among the panel of experts. Clinical practice was deemed 'recommended' if 50-74% of the experts reached agreement and 'highly recommended' if 75% or more of the experts reached agreement. RESULTS: Fifty VATS lobectomy experts (91%) from 16 countries completed both rounds of standardized questionnaires. No statistically significant differences in the responses between the two rounds of questioning were identified. Consensus was reached on 21 controversial points, outlining the current accepted definition of VATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions. CONCLUSION: The present Consensus Statement represents a collective agreement among 50 international experts to establish a standardized practice of VATS lobectomy for the thoracic surgical community after 20 years of clinical experience. The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx (Nature, (2023), 616, 7957, (525-533), 10.1038/s41586-023-05783-5)
No full textCorrection to: Naturehttps://doi.org/10.1038/s41586-023-05783-5 Published online 12 April 2023 In the version of the article initially published, the symbols for death (x) and censored (>) were swapped in the graphs in Fig. 1. The figure has now been corrected in the HTML and PDF versions of the article
Neoantigen-directed immune escape in lung cancer evolution
No full textThe interplay between an evolving cancer and a dynamic immune microenvironment remains unclear. Here we analyse 258 regions from 88 early-stage, untreated non-small-cell lung cancers using RNA sequencing and histopathology-assessed tumour-infiltrating lymphocyte estimates. Immune infiltration varied both between and within tumours, with different mechanisms of neoantigen presentation dysfunction enriched in distinct immune microenvironments. Sparsely infiltrated tumours exhibited a waning of neoantigen editing during tumour evolution, indicative of historical immune editing, or copy-number loss of previously clonal neoantigens. Immune-infiltrated tumour regions exhibited ongoing immunoediting, with either loss of heterozygosity in human leukocyte antigens or depletion of expressed neoantigens. We identified promoter hypermethylation of genes that contain neoantigenic mutations as an epigenetic mechanism of immunoediting. Our results suggest that the immune microenvironment exerts a strong selection pressure in early-stage, untreated non-small-cell lung cancers that produces multiple routes to immune evasion, which are clinically relevant and forecast poor disease-free survival.sponsorship: We thank the members of the TRACERx consortium for participating in this study. C.S. is Royal Society Napier Research Professor. C.S. is supported by the Francis Crick Institute, which receives its core funding from the Medical Research Council (FC001169), the Wellcome Trust (FC001169), and Cancer Research UK (FC001169). C.S. is funded by Cancer Research UK (TRACERx and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence, Stand Up 2 Cancer (SU2C), the Rosetrees and Stoneygate Trusts, NovoNordisk Foundation (ID 16584), the Breast Cancer Research Foundation (BCRF), the European Research Council Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet-607722), Chromavision (this project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 665233), National Institute for Health Research (NIHR), the University College London Hospitals Biomedical Research Centre (BRC) and the Cancer Research UK University College London Experimental Cancer Medicine Centre. N.M. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (211179/Z/18/Z), and also receives funding from CRUK Lung Cancer Centre of Excellence, Rosetrees and the University College London Hospitals Biomedical Research Centre (BRC) and the Cancer Research UK University College London Experimental Cancer Medicine Centre. E.L.C., J.D. and P.V.L. are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001202), the UK Medical Research Council (FC001202), and the Wellcome Trust (FC001202). P.V.L. is a Winton Group Leader in recognition of the Winton Charitable Foundation's support towards the establishment of The Francis Crick Institute. J.D. is a postdoctoral fellow of the Research Foundation -Flanders (FWO). S.A.Q. is funded by a CRUK Senior Cancer Research Fellowship (C36463/A22246), a CRUK Biotherapeutic Program Grant (C36463/A20764), the Cancer Immunotherapy Accelerator Award (CITA-CRUK) (C33499/A20265) and Rosetrees. M.T. received funding from the People Programme Marie Curie Actions (FP7/2007-2013/WHRI-ACADEMY-608765) and the Danish Council for Strategic Research (1309-00006B). The TRACERx study (Clinicaltrials. gov no: NCT01888601) is sponsored by University College London (UCL/12/0279) and has been approved by an independent Research Ethics Committee (13/LO/1546). TRACERx is funded by Cancer Research UK (C11496/A17786) and coordinated through the Cancer Research UK and UCL Cancer Trials Centre. For the RRBS methylation data, we acknowledge technical support from the CRUK-UCL Centre-funded Genomics and Genome Engineering Core Facility of the UCL Cancer Institute and grant support from the NIHR BRC (BRC275/CN/SB/101330). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The results published here are based in part upon data generated by The Cancer Genome Atlas pilot project established by the NCI and the National Human Genome Research Institute. The data were retrieved through database of Genotypes and Phenotypes (dbGaP) authorization (accession number phs000178.v9.p8). Information about TCGA and the constituent investigators and institutions the TCGA research network can be found at http://cancergenome.nih.gov/. (Francis Crick Institute - Medical Research Council|FC001169, Wellcome Trust|FC001169, Wellcome Trust|211179/Z/18/Z, Wellcome Trust|FC001202, Cancer Research UK|FC001169, Cancer Research UK|C11496/A17786, Cancer Research UK (TRACERx), CRUK Lung Cancer Centre of Excellence, Stand Up 2 Cancer (SU2C), Rosetrees Trust, Stoneygate Trust, NovoNordisk Foundation|16584, Breast Cancer Research Foundation (BCRF), European Research Council Consolidator Grant|FP7-THESEUS-617844, European Commission ITN|FP7-PloidyNet-607722, Chromavision (European Union's Horizon 2020 research and innovation programme)|665233, National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre (BRC), Cancer Research UK University College London Experimental Cancer Medicine Centre, Royal Society|211179/Z/18/Z, Rosetrees, Francis Crick Institute - Cancer Research UK|FC001202, UK Medical Research Council|FC001202, Winton Charitable Foundation, CRUK Senior Cancer Research Fellowship|C36463/A22246, CRUK Biotherapeutic Program Grant|C36463/A20764, Cancer Immunotherapy Accelerator Award (CITA-CRUK)|C33499/A20265, People Programme Marie Curie Actions|FP7/2007-2013/WHRI-ACADEMY-608765, Danish Council for Strategic Research|1309-00006B, University College London|UCL/12/0279, CRUK-UCL Centre, NIHR BRC|BRC275/CN/SB/101330, Cancer Research UK (CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK|23896, Cancer Research UK|19278, Cancer Research UK|24314, Cancer Research UK|20466, Cancer Research UK|28990, Cancer Research UK|20764, Cancer Research UK|16463, Cancer Research UK|20465, Cancer Research UK|17786, Cancer Research UK|21999, Cancer Research UK|24956, Cancer Research UK; Versus Arthritis|22246, Cancer Research UK; Versus Arthritis|20265, Medical Research Council|MC_UP_1203/1, National Institute for Health Research|CL-2015-18-009, National Institute for Health Research|CL-2015-17-002, Novo Nordisk Fonden|NNF15OC0016584, Rosetrees|M179, Rosetrees|M630, The Francis Crick Institute|10169, The Francis Crick Institute|10202, The Francis Crick Institute|10002, The Francis Crick Institute|10233, Wellcome Trust|107963/Z/15/Z, Wellcome Trust|211179/Z/18/Z)status: Publishe
Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): a multi-centre, randomised, blinded, placebo controlled trial
No full textBackground: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. / Methods: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. / Findings: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). / Interpretation: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. / Funding: UK National Institute for Health Research Health Technology Assessment
Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial
No full textBackground Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events
