Labour exchange

This exhibition brings together works by painter Sarah Taylor and photography practitioner Magali Nougarède. ‘Labour Exchange’ was initially developed with Helen Sear who noticed similarities in Nougarède and Taylor’s practices. Research process: In their practice research, both artists use the domestic object as source material, especially soft furnishings re-appropriated from previous generations: fabrics, clothing, wallpaper, cloths, tea towels. These items are at the centre of the artists’ visual consciousness, both as objects of aesthetic fascination and as objects of historical and political significance. Taylor’s grandmother coveted objects to make her home look respectable, whilst Nougarède’s protestant family was entrenched in the production of linen, cottons and tea towels in the 19th and 20th century Normandy textile industry. Both artists see the domestic object as an opportunity to interrogate power relations, past and present, in terms of gender, class (especially in Taylor’s case) and political ideology, to address political inequities and reclaim histories. Research insights: Traditionally photography has been seen as inferior to painting, however it is the contemporary photographic discourse, defined by thinkers and writers such as Jo Spence, Annette Kuhn and John Tagg, that helps articulate some of the ideas for this exhibition. Both artists thrive on playing outside the boundaries of their own medium, contesting the parameters of both painting and photography. Conforming is not an option. Some of Taylor’s paintings made by direct application of paint laden fabric or cloth unto the canvass, at times adopt qualities of photographic exactness, whilst Nougarede’s high contrast enlarged tea towel grids printed on cotton rag paper may recall pencil marks on drawing paper. Dissemination: The exhibition was disseminated at BayArt Gallery, Bute Street, Cardiff Bay. Helen Sear led a pre-preview “In conversation” with artists Magali Nougarède and Sarah Taylor titled: A gendered perspective?

The role of computer-assisted radiographer reporting in lung cancer screening programmes

OBJECTIVES: Successful lung cancer screening delivery requires sensitive, timely reporting of low-dose computed tomography (LDCT) scans, placing a demand on radiology resources. Trained non-radiologist readers and computer-assisted detection (CADe) software may offer strategies to optimise the use of radiology resources without loss of sensitivity. This report examines the accuracy of trained reporting radiographers using CADe support to report LDCT scans performed as part of the Lung Screen Uptake Trial (LSUT). METHODS: In this observational cohort study, two radiographers independently read all LDCT performed within LSUT and reported on the presence of clinically significant nodules and common incidental findings (IFs), including recommendations for management. Reports were compared against a 'reference standard' (RS) derived from nodules identified by study radiologists without CADe, plus consensus radiologist review of any additional nodules identified by the radiographers. RESULTS: A total of 716 scans were included, 158 of which had one or more clinically significant pulmonary nodules as per our RS. Radiographer sensitivity against the RS was 68-73.7%, with specificity of 92.1-92.7%. Sensitivity for detection of proven cancers diagnosed from the baseline scan was 83.3-100%. The spectrum of IFs exceeded what could reasonably be covered in radiographer training. CONCLUSION: Our findings highlight the complexity of LDCT reporting requirements, including the limitations of CADe and the breadth of IFs. We are unable to recommend CADe-supported radiographers as a sole reader of LDCT scans, but propose potential avenues for further research including initial triage of abnormal LDCT or reporting of follow-up surveillance scans. KEY POINTS: • Successful roll-out of mass screening programmes for lung cancer depends on timely, accurate CT scan reporting, placing a demand on existing radiology resources. • This observational cohort study examines the accuracy of trained radiographers using computer-assisted detection (CADe) software to report lung cancer screening CT scans, as a potential means of supporting reporting workflows in LCS programmes. • CADe-supported radiographers were less sensitive than radiologists at identifying clinically significant pulmonary nodules, but had a low false-positive rate and good sensitivity for detection of confirmed cancers

Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.

BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening

Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis

BACKGROUND: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). METHODS: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. RESULTS: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). INTERPRETATION: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression

The chlorine isotopic composition of the Moon: Insights from melt inclusions

The Moon exhibits a heavier chlorine (Cl) isotopic composition compared to the Earth. Several hypotheses have been put forward to explain this difference, based mostly on analyses of apatite in lunar samples complemented by bulk-rock data. The earliest hypothesis argued for Cl isotope fractionation during the degassing of anhydrous basaltic magmas on the Moon. Subsequently, other hypotheses emerged linking Cl isotope fractionation on the Moon with the degassing during the crystallization of the Lunar Magma Ocean (LMO). Currently, a variant of the LMO degassing model involving mixing between two end-member components, defined by early-formed cumulates, from which mare magmas were subsequently derived, and a KREEP component, which formed towards the end of the LMO crystallization, seems to reconcile some existing Cl isotope data on lunar samples. To further ascertain the history of Cl in the Moon and to investigate any evolution of Cl during magma crystallization and emplacement events, which could help resolve the chlorine isotopic variation between the Earth and the Moon, we analysed the Cl abundance and its isotopic composition in 36 olivine- and pyroxene-hosted melt inclusions (MI) in five Apollo basalts (10020, 12004, 12040, 14072 and 15016). Olivine-hosted MI have an average of 3.3 ± 1.4 ppm Cl. Higher Cl abundances (11.9 ppm on average) are measured for pyroxene-hosted MI, consistent with their formation at later stages in the crystallization of their parental melt compared to olivines. Chlorine isotopic composition (δ37) of MI in the five Apollo basalts have weighted averages of +12 ± 2.4‰ and +10.1 ± 3.2‰ for olivine- and pyroxene-hosted MI, respectively, which are statistically indistinguishable. These isotopic compositions are also similar to those measured in apatite in these lunar basalts, with the exception of sample 14072, which is known to have a distinct petrogenetic history compared to other mare basalts. Based on our dataset, we conclude that, post-MI-entrapment, no significant Cl isotopic fractionation occurred during the crystallization and subsequent eruption of the parent magma and that Cl isotopic composition of MI and apatite primarily reflect the signature of the source region of these lunar basalts. Our findings are compatible with the hypothesis that in the majority of the cases the heavy Cl isotopic signature of the Moon was acquired during the earliest stages of LMO evolution. Interestingly, MI data from 14072 suggests that Apollo 14 lunar basalts might be an exception and may have experienced post-crystallization processes, possibly metasomatism, resulting in additional Cl isotopic fractionation recorded by apatite but not melt inclusions

Toward interoperable bioscience data

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Genetics 44 (2012): 121-126, doi:10.1038/ng.1054.To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision.The authors also acknowledge the following funding sources in particular: UK Biotechnology and Biological Sciences Research Council (BBSRC) BB/I000771/1 to S.-A.S. and A.T.; UK BBSRC BB/I025840/1 to S.-A.S.; UK BBSRC BB/I000917/1 to D.F.; EU CarcinoGENOMICS (PL037712) to J.K.; US National Institutes of Health (NIH) 1RC2CA148222-01 to W.H. and the HSCI; US MIRADA LTERS DEB-0717390 and Alfred P. Sloan Foundation (ICoMM) to L.A.-Z.; Swiss Federal Government through the Federal Office of Education and Science (FOES) to L.B. and I.X.; EU Innovative Medicines Initiative (IMI) Open PHACTS 115191 to C.T.E.; US Department of Energy (DOE) DE-AC02- 06CH11357 and Arthur P. Sloan Foundation (2011- 6-05) to J.G.; UK BBSRC SysMO-DB2 BB/I004637/1 and BBG0102181 to C.G.; UK BBSRC BB/I000933/1 to C.S. and J.L.G.; UK MRC UD99999906 to J.L.G.; US NIH R21 MH087336 (National Institute of Mental Health) and R00 GM079953 (National Institute of General Medical Science) to A.L.; NIH U54 HG006097 to J.C. and C.E.S.; Australian government through the National Collaborative Research Infrastructure Strategy (NCRIS); BIRN U24-RR025736 and BioScholar RO1-GM083871 to G.B. and the 2009 Super Science initiative to C.A.S

Predictive integration of gene functional similarity and co-expression defines treatment response of endothelial progenitor cells

<p>Abstract</p> <p>Background</p> <p>Endothelial progenitor cells (EPCs) have been implicated in different processes crucial to vasculature repair, which may offer the basis for new therapeutic strategies in cardiovascular disease. Despite advances facilitated by functional genomics, there is a lack of systems-level understanding of treatment response mechanisms of EPCs. In this research we aimed to characterize the EPCs response to adenosine (Ado), a cardioprotective factor, based on the systems-level integration of gene expression data and prior functional knowledge. Specifically, we set out to identify novel biosignatures of Ado-treatment response in EPCs.</p> <p>Results</p> <p>The predictive integration of gene expression data and standardized functional similarity information enabled us to identify new treatment response biosignatures. Gene expression data originated from Ado-treated and -untreated EPCs samples, and functional similarity was estimated with Gene Ontology (GO)-based similarity information. These information sources enabled us to implement and evaluate an integrated prediction approach based on the concept of <it>k</it>-nearest neighbours learning (<it>k</it>NN). The method can be executed by expert- and data-driven input queries to guide the search for biologically meaningful biosignatures. The resulting <it>integrated kNN </it>system identified new candidate EPC biosignatures that can offer high classification performance (areas under the operating characteristic curve > 0.8). We also showed that the proposed models can outperform those discovered by standard gene expression analysis. Furthermore, we report an initial independent <it>in vitro </it>experimental follow-up, which provides additional evidence of the potential validity of the top biosignature.</p> <p>Conclusion</p> <p>Response to Ado treatment in EPCs can be accurately characterized with a new method based on the combination of gene co-expression data and GO-based similarity information. It also exploits the incorporation of human expert-driven queries as a strategy to guide the automated search for candidate biosignatures. The proposed biosignature improves the systems-level characterization of EPCs. The new integrative predictive modeling approach can also be applied to other phenotype characterization or biomarker discovery problems.</p

Tracking genomic cancer evolution for precision medicine: The Lung TRACERx Study

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relaps

Chest radiograph classification and severity of suspected COVID-19 by different radiologist groups and attending clinicians: multi-reader, multi-case study.

OBJECTIVES: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. METHODS: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. RESULTS: Agreement with consensus for the indeterminate category was low across all groups (28-37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66-76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54-61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84-95%). For all groups, agreement for changes across paired CXRs was modest. CONCLUSION: Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. KEY POINTS: • Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. • Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. • Agreement for serial CXR change is moderate, limiting utility in guiding management