The Carboniferous carbon isotope record from sedimentary organic matter: can we disentangle the carbon cycle?

A comprehensive analysis of the 13C composition of sedimentary organic matter from Euramerican Carboniferous successions indicates there are significant shifts in 13C through this key time interval. Our studies have revealed that, at an individual location, the source and delivery mechanism of the sediment contribute to the type of organic matter preserved and, in turn this influences the measured 13C values from bulk sedimentary organic matter of organic matter

Rebuilding terrestrial ecosystems after the end-Devonian mass extinction: insights from the TW:eed Project

The TW:eed (Tetrapod World: early evolution and diversification) project is a major research initiative that will generate a coherent picture of the biotic, environmental and geological conditions of the 15-20 million years recovery period following the major extinction event at the end-Devonian that was a major turning point in terrestrial evolution. A paucity of terrestrial invertebrates and few fossils of early tetrapods have been found in post-Devonian successions from the immediate aftermath (Romer’s Gap) and yet, during a relatively brief time period in the Early Carboniferous, fully terrestrial vertebrates evolved, terrestrial arthropods radiated, ray-finned fishes took over from lobe-finned forms and plant groups diversified. Several new localities in Carboniferous successions in southern Scotland and northern England are providing completely new insights into this pivotal period for the evolution of life on land. Significant new tetrapod material is helping to populate Romer’s Gap. Localities are also yielding a diverse fauna of fish (gyracanthids, lungfish, rhizodonts and actinopterygians), invertebrates (malacostracans, eurypterids, ostracods, scorpions and myriapods) and plants. The fossil localities are within the Ballagan Formation, a distinctive unit comprising mudstones with interbedded sandstones, palaeosols and thin beds of dolomitic “cementstone”. The sediments were deposited on an extensive low relief, muddy, vegetated floodplain that was traversed by numerous river systems. Periodically the river-derived floods submerged the floodplains generating extensive shallow freshwater lakes. The presence of gypsum and anhydrite indicates that there were occasional marine transgressions across a marginal coastal plain. So far, most of the fossils have been found towards the top of the Ballagan Formation, but a coastal exposure of the entire formation provides a unique opportunity to search for fossils across a time interval of about 15 million years at the base of the Carboniferous. In addition to the detailed analysis of key outcrops, a drilling program in the Tweed Basin is in the process of acquiring 500 m of continuous core through these earliest Carboniferous successions. A tight stratigraphic framework for tetrapod localities across the region will be generated by integrating the sedimentological (lithostratigraphy), micropalaeontological (biostratigraphy), chemostratigraphical (carbon and oxygen stable isotopes) and petrophysical data from the core and outcrops. The borehole will provide the high-resolution datasets required to investigate the local, and potentially, global palaeoclimate and its evolution through this time interval. This multifaceted project is a unique opportunity to examine the progression, causes and context of the rebuilding of an ecosystem following a major extinction

Tests of sunspot number sequences: 1. Using ionosonde data

More than 70 years ago it was recognised that ionospheric F2-layer critical frequencies [foF2] had a strong relationship to sunspot number. Using historic datasets from the Slough and Washington ionosondes, we evaluate the best statistical fits of foF2 to sunspot numbers (at each Universal Time [UT] separately) in order to search for drifts and abrupt changes in the fit residuals over Solar Cycles 17-21. This test is carried out for the original composite of the Wolf/Zürich/International sunspot number [R], the new “backbone” group sunspot number [RBB] and the proposed “corrected sunspot number” [RC]. Polynomial fits are made both with and without allowance for the white-light facular area, which has been reported as being associated with cycle-to-cycle changes in the sunspot number - foF2 relationship. Over the interval studied here, R, RBB, and RC largely differ in their allowance for the “Waldmeier discontinuity” around 1945 (the correction factor for which for R, RBB and RC is, respectively, zero, effectively over 20 %, and explicitly 11.6 %). It is shown that for Solar Cycles 18-21, all three sunspot data sequences perform well, but that the fit residuals are lowest and most uniform for RBB. We here use foF2 for those UTs for which R, RBB, and RC all give correlations exceeding 0.99 for intervals both before and after the Waldmeier discontinuity. The error introduced by the Waldmeier discontinuity causes R to underestimate the fitted values based on the foF2 data for 1932-1945 but RBB overestimates them by almost the same factor, implying that the correction for the Waldmeier discontinuity inherent in RBB is too large by a factor of two. Fit residuals are smallest and most uniform for RC and the ionospheric data support the optimum discontinuity multiplicative correction factor derived from the independent Royal Greenwich Observatory (RGO) sunspot group data for the same interval

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A phase II study of fenretinide in patients with hormone refractory prostate cancer: a trial of the Cancer Therapeutics Research Group

10.1007/s00280-009-1228-xCancer Chemotherapy and Pharmacology1-