Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Isoprene hotspots at the Western Coast of Antarctic Peninsula during MASEC′16

Isoprene (C5H8) plays an important role in the formation of surface ozone (O3) and the secondary organic aerosol (SOA) which contributed to the climate change. This study aims to determine hourly distribution of tropospheric isoprene over the Western Coast of Antarctic Peninsula (WCAP) during the Malaysian Antarctic Scientific Expedition Cruise 2016 (MASEC′16). In-situ measurements of isoprene were taken using a custom-built gas chromatography with photoionization detector, known as iDirac. Biological parameters such as chlorophyll a (chl-a) and particulate organic carbon (POC) were compared to the in-situ isoprene measurements. Significant positive correlation was observed between isoprene and POC concentrations (r2 = 0.67, p < 0.001), but not between isoprene and chl-a. The hotspots of isoprene over maritime Antarctic were then were investigated using NAME dispersion model reanalysis. Measurements showed that isoprene mixing ratio were the highest over region of King George Island, Deception Island and Booth Island with values of ∼5.0, ∼0.9 and ∼5.2 ppb, respectively. Backward trajectory analysis showed that air masses may have lifted the isoprene emitted by marine algae. We believe our findings provide valuable data set of isoprene estimation over the under sampled WCAP

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

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

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

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

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

Slipfaceless 'whaleback' dunes in a polar desert, Victoria Valley, Antarctica: Insights from ground penetrating radar

The Lower Victoria Valley is one of the McMurdo Dry Valleys, Antarctica, and has the largest concentration of aeolian sand dunes on the continent. Aeolian bedforms include elongate slipfaceless dunes which have been called ‘whaleback’ dunes. These dunes are composed of coarse sand and capped by granule ripples. Ground penetrating radar (GPR) profiles across one of these dunes reveal low-angle inclined sigmoid/tangential and convex reflections that are interpreted as strata within the dune. These dipping strata record the migration of the whaleback dune and show that they are not sand mantles as previously described but are actively migrating, long-wavelength, low-amplitude bedforms resembling zibar. An 800 m profile along the axis of the dune reveals low-angle dips from west to east showing that the dune has accreted towards the east. GPR profiles collected at 100 m intervals transverse to the dune axis reveal sets of cross-stratification dipping towards the south at the eastern end of the dune and towards the north at its western end. These apparent dips are resolved to show that the dune has migrated from west to east, driven by westerly foehn winds and katabatic winds blowing from the Polar ice cap, whilst at the same time it has been building obliquely towards the south. Accretion towards the north at the western end of the dune is attributed to reworking of the dune sand by easterly winds blowing inland from McMurdo Sound. An unconformity within the dune suggests that the wind regime has varied in the past. Beneath the unconformity the direction of dune migration was from west to east, and eastward extension of the dune continues at the present day. However, this is combined with accretion towards the north and west at the western end of the dune which is not recorded in the older sediments beneath the unconformity. Sand wedge structures that may have taken hundreds to thousands of years to form are found within the dune, and suggest that arid conditions suitable for dune construction have persisted in Victoria Valley for a considerable time

Investigation of the age and migration of reversing dunes in Antarctica using GPR and OSL, with implications for GPR on Mars

GPR provides high resolution images of aeolian strata in frozen sand in the McMurdo Dry Valleys of Antarctica. The results have positive implications for potential GPR surveys of aeolian strata on Mars. Within the Lower Victoria Valley, seasonal changes in climate and a topographically-constrained wind regime result in significant wind reversals. As a consequence, dunes show reversing crest-lines and flattened dune crests. Ground-penetrating radar (GPR) surveys of the dunes reveal sets of cross-strata and low-angle bounding surfaces produced by reversing winds. Summer sand transport appears to be dominant and this is attributed to the seasonal increase in solar radiation. Solar radiation which heats the valley floor melts ice cements making sand available for transport. At the same time, solar heating of the valley floor generates easterly winds that transport the sand, contributing to the resultant westward dune migration. The location of the dune field along the northern edge of the Lower Victoria Valley provides some shelter from the powerful föehn and katabatic winds that sweep down the valley. Topographic steering of the winds along the valley and drag against the valley wall has probably aided the formation, migration and preservation of the dune field. Optically-stimulated luminescence (OSL) ages from dune deposits range from 0 to 1.3 kyr showing that the dune field has been present for at least 1000 yr. The OSL ages are used to calculate end-point migration rates of 0.05 to 1.3 m/yr, which are lower than migration rates reported from recent surveys of the Packard dunes and lower than similar-sized dunes in low-latitude deserts. The relatively low rates of migration are attributed to a combination of dune crest reversal under a bimodal wind regime and ice cement that reduces dune deflation and restricts sand entrainment