Major ice‐sheet change in the Weddell Sector of West Antarctica over the last 5000 years

Until recently, little was known about the Weddell Sea sector of the West Antarctic Ice Sheet. In the last 10 years, a variety of expeditions and numerical modelling experiments have improved knowledge of its glaciology, glacial geology, and tectonic setting. Two of the sector's largest ice streams rest on a steep reverse‐sloping bed yet, despite being vulnerable to change, satellite observations show contemporary stability. There is clear evidence for major ice‐sheet reconfiguration in the last few thousand years, however. Knowing precisely how the ice sheet has changed in the past, and when, would allow us to better understand whether it is now at risk. Two competing hypotheses have been established for this glacial history. In one, the ice sheet retreated and thinned progressively from its Last Glacial Maximum position. Retreat stopped at, or very near, the present position in the Late Holocene. Alternatively, in the Late Holocene the ice sheet retreated significantly upstream of the present grounding line, and then advanced to the present location due to glacial isostatic adjustment, and ice‐shelf and ice rise buttressing. Both hypotheses point to data and theory in their support, yet neither has been unequivocally tested or falsified. Here, we review geophysical evidence to determine how each hypothesis has been formed, where there are inconsistencies in the respective glacial histories, how they may be tested or reconciled, and what new evidence is required to reach a common model for the Late Holocene ice sheet history of the Weddell Sea sector of West Antarctica

Growth and mortality of coccolithophores during spring in a temperate Shelf Sea (Celtic Sea, April 2015)

Coccolithophores are key components of phytoplankton communities, exerting a critical impact on the global carbon cycle and the Earth’s climate through the production of coccoliths made of calcium carbonate (calcite) and bioactive gases. Microzooplankton grazing is an important mortality factor in coccolithophore blooms, however little is currently known regarding the mortality (or growth) rates within non-bloom populations. Measurements of coccolithophore calcite production (CP) and dilution experiments to determine microzooplankton (≤63 µm) grazing rates were made during a spring cruise (April 2015) at the Central Celtic Sea (CCS), shelf edge (CS2), and within an adjacent April bloom of the coccolithophore Emiliania huxleyi at station J2. CP at CCS ranged from 10.4 to 40.4 µmol C m−3 d−1 and peaked at the height of the spring phytoplankton bloom (peak chlorophyll-a concentrations ∼6 mg m−3). Cell normalised calcification rates declined from ∼1.7 to ∼0.2 pmol C cell−1 d−1, accompanied by a shift from a mixed coccolithophore species community to one dominated by the more lightly calcified species E. huxleyi and Calciopappus caudatus. At the CCS, coccolithophore abundance increased from 6 to 94 cells mL−1, with net growth rates ranging from 0.06 to 0.21 d−1 from the 4th to the 28th April. Estimates of intrinsic growth and grazing rates from dilution experiments, at the CCS ranged from 0.01 to 0.86 d−1 and from 0.01 to 1.32 d−1, respectively, which resulted in variable net growth rates during April. Microzooplankton grazers consumed 59 to >100% of daily calcite production at the CCS. Within the E. huxleyi bloom a maximum density of 1986 cells mL−1 was recorded, along with CP rates of 6000 µmol C m−3 d−1 and an intrinsic growth rate of 0.29 d−1, with ∼80% of daily calcite production being consumed. Our results show that microzooplankton can exert strong top-down control on both bloom and non-bloom coccolithophore populations, grazing over 60% of daily growth (and calcite production). The fate of consumed calcite is unclear, but may be lost either through dissolution in acidic food vacuoles, and subsequent release as CO2, or export to the seabed after incorporation into small faecal pellets. With such high microzooplankton-mediated mortality losses, the fate of grazed calcite is clearly a high priority research direction

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Search for annual and diurnal rate modulations in the LUX experiment

Various dark matter models predict annual and diurnal modulations of dark matter interaction rates in Earth-based experiments as a result of the Earth’s motion in the halo. Observation of such features can provide generic evidence for detection of dark matter interactions. This paper reports a search for both annual and diurnal rate modulations in the LUX dark matter experiment using over 20 calendar months of data acquired between 2013 and 2016. This search focuses on electron recoil events at low energies, where leptophilic dark matter interactions are expected to occur and where the DAMA experiment has observed a strong rate modulation for over two decades. By using the innermost volume of the LUX detector and developing robust cuts and corrections, we obtained a stable event rate of 2.3±0.2  cpd/keVee/tonne, which is among the lowest in all dark matter experiments. No statistically significant annual modulation was observed in energy windows up to 26  keVee. Between 2 and 6  keVee, this analysis demonstrates the most sensitive annual modulation search up to date, with 9.2σ tension with the DAMA/LIBRA result. We also report no observation of diurnal modulations above 0.2  cpd/keVee/tonne amplitude between 2 and 6  keVee.Various dark matter models predict annual and diurnal modulations of dark matter interaction rates in Earth-based experiments as a result of the Earth's motion in the halo. Observation of such features can provide generic evidence for detection of dark matter interactions. This paper reports a search for both annual and diurnal rate modulations in the LUX dark matter experiment using over 20 calendar months of data acquired between 2013 and 2016. This search focuses on electron recoil events at low energies, where leptophilic dark matter interactions are expected to occur and where the DAMA experiment has observed a strong rate modulation for over two decades. By using the innermost volume of the LUX detector and developing robust cuts and corrections, we obtained a stable event rate of 2.3$\pm$0.2~cpd/keV$_{\text{ee}}$/tonne, which is among the lowest in all dark matter experiments. No statistically significant annual modulation was observed in energy windows up to 26~keV$_{\text{ee}}$. Between 2 and 6~keV$_{\text{ee}}$, this analysis demonstrates the most sensitive annual modulation search up to date, with 9.2$\sigma$ tension with the DAMA/LIBRA result. We also report no observation of diurnal modulations above 0.2~cpd/keV$_{\text{ee}}$/tonne amplitude between 2 and 6~keV$_{\text{ee}}$

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p

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

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

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Measurement of the Bs0→ μμ effective lifetime with the ATLAS detector

This paper reports the first ATLAS measurement of the B0s → μμ effective lifetime. The measurement is based on the data collected in 2015–2016, amounting to 26.3 fb−1 of 13 TeV LHC proton-proton collisions. The proper decay-time distribution of 58 ± 13 background-subtracted signal candidates is fit with simulated signal templates parameterised as a function of the B0s effective lifetime, with statistical uncertainties extracted through a Neyman construction. The resulting effective measurement of the B0s → μμ lifetime is 0.99+0.42−0.07 (stat.) ± 0.17 (syst.) ps and it is found to be consistent with the Standard Model