Effect of Grain Boundary Character Distribution on the Impact Toughness of 410NiMo Weld Metal

Grain boundary character distributions in 410NiMo weld metal were studied in the as-welded, first-stage, and second-stage postweld heat treatment (PWHT) conditions, and these were correlated with the Charpy-V impact toughness values of the material. The high impact toughness values in the weld metal in the as-welded and first-stage PWHT conditions compared to that in the second-stage condition are attributed to the higher fraction of low-energy I pound boundaries. A higher volume fraction of retained austenite and coarser martensite after second-stage PWHT accompanied by the formation of the ideal cube component in the 2-hour heat-treated specimen led to a reduction in the toughness value. A subsequent increase in the PWHT duration at 873 K (600 A degrees C) enhanced the formation of {111}aOE (c) 112 >, which impedes the adverse effect of the cubic component, resulting in an increase in the impact toughness. In addition to this, grain refinement during 4-hour PWHT in the second stage also increased the toughness of the weld metal

Dexamethasone in hospitalized patients with Covid-19

BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment.ResultsA total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55).ConclusionsIn patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936. opens in new tab; ISRCTN number, 50189673. opens in new tab.

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Analysing the timing of peak warming and minimum winter sea-ice extent in the Southern Ocean during MIS 5e

The peak of the Last Interglacial, Marine Isotope Stage (MIS) 5e (130–116 ka), provides a valuable ‘process analogue’ for validating the climatic feedbacks and forcings likely active under future anthropogenic warming. Reconstructing exact timings of MIS 5e peak warming and minimum winter sea-ice extent (WSIE) throughout the Southern Ocean (SO) will help to identify the interactions and feedbacks within the ice-ocean system. Here we present a new MIS 5e marine sediment record from the SW Atlantic sector together with 28 published core records (chronologies standardised to the LR04 δ18O benthic stack; Lisiecki and Raymo, 2005) to investigate the timing and sequence of minimum WSIE and peak warming across the SO. Sea-surface temperatures (SSTs) peaked earliest in the Indian (20oE–150oE) and Atlantic (70oW–20oE) sectors, at 128.7 ± 0.8 ka and 127.4 ± 1.1 ka respectively, followed by the Pacific sector (150oE–70oW) at 124.9 ± 3.6 ka. The interval of minimum WSIE for all three sectors occurred within the period from 129–125 ka, consistent with the ∼128 ka sea salt flux minimum in Antarctic ice cores. Minimum WSIE appears to have coincided with peak July insolation at 55 oS, suggesting it could be linked with the mildest winters. The reduced WSIE during MIS 5e would have likely reduced the production of deep- and bottom water masses, inhibiting storage of CO2 in the abyssal ocean and lowering nutrient availability in SO surface waters. Examining a wide spatial range of proxy records for MIS 5e is a critical step forward in understanding climatic interactions and processes that will be active under warmer global temperatures

Reconstructing Antarctic winter sea-ice extent during Marine Isotope Stage (MIS) 5e

MIS 5e (130-116 ka) is an important ‘process analogue’ for understanding the high latitude climatic feedbacks and forcings active under future anthropogenic warming. Antarctic sea-ice extent is a critical component of the Earth’s climate system through its impact on global albedo and Southern Hemisphere atmospheric and ocean circulation. Published marine sediment core records are located too far north to accurately constrain the timing and extent of the winter sea-ice (WSI) minimum during MIS 5e (Chadwick et al., 2020) and researchers/models have therefore assumed that this minimum occurs synchronously with peak warming in Antarctic ice core records (Holloway et al., 2017). This study presents new reconstructions of Southern Ocean (SO) WSI extent for MIS 5e based on the diatom assemblage records in marine sediment cores. These records have robust age models, which allow for the different timings and patterns of WSI retreat throughout the SO to be examined. In particular, the difference between the relatively stable WSI extent in the Pacific sector of the SO and the more dynamic WSI extent in the Atlantic sector of the SO. Using sediment cores located south of 55 o S creates a novel synthesis for assessing the evidence for the considerable MIS 5e WSI reduction predicted by model simulations (Holloway et al., 2017)

How does the Southern Ocean palaeoenvironment during Marine Isotope Stage 5e compare to the modern?

Marine Isotope Stage (MIS) 5e (130–116 ka) represents an important ‘process analogue’ for understanding the climatic feedbacks and responses likely active under future anthropogenic warming. Reconstructing the Southern Ocean (SO) palaeoenvironment during MIS 5e and comparing it to the present day provides insights into the different responses of the SO sectors to a warmer climate. This study presents new records from seven marine sediment cores for MIS 5e together with their surface sediment records; all cores are located south of 55 oS. We investigate changes in diatom species assemblage and the accompanying variations in sea surface temperatures, winter sea-ice extent (WSIE) and glacial meltwater flux. All records show warmer conditions and a reduced WSIE during MIS 5e relative to the surface sediments. While the Pacific and Indian Sector records present very stable conditions throughout MIS 5e, the Atlantic Sector records display much more changeable conditions, particularly with respect to the WSIE. These variable conditions are attributed to higher iceberg and glacial meltwater flux in the Weddell Sea. This evidence for increased iceberg and glacial meltwater flux in the Weddell Sea during MIS 5e may have significant implications for understanding the stability of the West Antarctic Ice Sheet, both during MIS 5e and under future warming