15 research outputs found

    Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

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    The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

    Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

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    SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

    Designing their own Future: Teaching Students how to Design Aerospace Operations Research

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    This paper tells of the development of a course designed to help students set up their own operations research projects. The course was taught in a lecture format with much room for interaction and the students were required to make submit formal research plans for their operations research projects as well as literature review. The initial results from course evaluations show a significant improvement in student’s self-perceived level of preparedness for their Master thesis as well as a high satisfaction with the course itself.Aerospace Structures & MaterialsAerospace Engineerin

    Mapping the maze of assessment: an investigation into practice

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    “The final, definitive version of this article has been published in the Journal, Active Learning in Higher Education, 10 (2) pp.120-137, 2009, copyright SAGE Publications Ltd. on SAGE Journals Online: http://online.sagepub.com/ "This article presents the results of a preliminary survey of assessment tasks undertaken by students in higher education at a particular university. A key premise of the study was that the ability to handle assessment is central to the development of academic and professional literacy. Much of the current literature on assessment demonstrates a concern that it is not currently achieving this end. A grid of various features of assessment has been developed, onto which are mapped tasks used at all levels and within all disciplines in the institution. Considerable differences in the type and range of assessment tasks used across schools and disciplines are identified, and also a gap between the variation in tasks and the relatively narrow range of activities and techniques covered in most study skills manuals. It is argued that generic materials should broaden their base and that subject-specific material needs to be developed to accommodate the realities of lifelong learning.Peer reviewe

    Multiphase circumgalactic medium probed with MUSE and ALMA

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    Galaxy haloes appear to be missing a large fraction of their baryons, most probably hiding in the circumgalactic medium (CGM), a diffuse component within the dark matter halo that extends far from the inner regions of the galaxies. A powerful tool to study the CGM gas is offered by absorption lines in the spectra of background quasars. Here, we present optical (MUSE) and mm (ALMA) observations of the field of the quasar Q1130−1449 which includes a log [N(H I)/cm−2] = 21.71 ± 0.07 absorber at z = 0.313. Ground-based VLT/MUSE 3D spectroscopy shows 11 galaxies at the redshift of the absorber down to a limiting SFR > 0.01 M⊙ yr−1 (covering emission lines of [O II], Hβ, [O III], [N II], and H α), 7 of which are new discoveries. In particular, we report a new emitter with a smaller impact parameter to the quasar line of sight (b = 10.6 kpc) than the galaxies detected so far. Three of the objects are also detected in CO(1–0) in our ALMA observations indicating long depletion time-scales for the molecular gas and kinematics consistent with the ionized gas. We infer from dedicated numerical cosmological RAMSES zoom-in simulations that the physical properties of these objects qualitatively resemble a small group environment, possibly part of a filamentary structure. Based on metallicity and velocity arguments, we conclude that the neutral gas traced in absorption is only partly related to these emitting galaxies while a larger fraction is likely the signature of gas with surface brightness almost four orders of magnitude fainter that current detection limits. Together, these findings challenge a picture where strong-N(HI) quasar absorbers are associated with a single bright galaxy and favour a scenario where the H I gas probed in absorption is related to far more complex galaxy structures

    Breaking Bad: Public Pensions and the Loss of that Old-Time Fiscal Religion

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    Digital Currencies: Principles, Trends, Opportunities, and Risks

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