The Transformation of Sediment Into Rock : Insights From IODP Site U1352, Canterbury Basin, New Zealand

ACKNOWLEDGMENTS We thank the crew of the RV JOIDES Resolution for professional seamanship, excellent drilling, and the scientific support on board. GHB and SCG thank the Australia–New Zealand IODP Consortium (ANZIC), and KMM thanks the Consortium for Ocean Leadership U.S. Science Support Program for partly funding this work. Thanks also to funding agencies of the respective authors, and Mark Lawrence (GNS Science) and Cam Nelson (University of Waikato) for their thoughtful comments on an earlier draft. Karsten Kroeger (GNS Science) helped by providing compaction data for New Zealand basins, and Michelle Kominz (Western Michigan University) provided data on which Figure 8 was developed. Further improvements were the result of thoughtful detailed reviews by Gemma Barrie, Bill Heins, Stan Paxton, Associate Editor Joe Macquaker, and Editor Leslie Melim.Peer reviewedPostprin

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial

Acknowledgements The study and article were funded by Novavax. We would like to thank all the study participants for their commitment to this study. We also acknowledge the investigators and their study teams for their hard work and dedication. In addition, we would like to thank the National Institute for Health Research, representatives from the Department of Health and Social Care laboratories and NHS Digital and the members of the UK Vaccine Task Force. Editorial support was provided by Kelly Cameron of Ashfield MedComms, an Inizio company Funding This work was funded by Novavax, and the sponsor had primary responsibility for study design, study vaccines, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission. LF reports a position as a prior full-time employee, now contractor to Novavax re-imbursed hourly for work performed on this study and in analyses and drafting this report. IC reports providing medical writing support for this work as an employee of NovavaxPeer reviewedPublisher PD

Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo

Long-lasting, latently infected resting CD4+ T cells are the greatest obstacle to obtaining a cure for HIV infection, as these cells can persist despite decades of treatment with antiretroviral therapy (ART). Estimates indicate that more than 70 years of continuous, fully suppressive ART are needed to eliminate the HIV reservoir1. Alternatively, induction of HIV from its latent state could accelerate the decrease in the reservoir, thus reducing the time to eradication. Previous attempts to reactivate latent HIV in preclinical animal models and in clinical trials have measured HIV induction in the peripheral blood with minimal focus on tissue reservoirs and have had limited effect2–9. Here we show that activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of ART-suppressed bone-marrow–liver–thymus (BLT) humanized mice and rhesus macaques infected with HIV and SIV, respectively. Analysis of resting CD4+ T cells from tissues after AZD5582 treatment revealed increased SIV RNA expression in the lymph nodes of macaques and robust induction of HIV in almost all tissues analysed in humanized mice, including the lymph nodes, thymus, bone marrow, liver and lung. This promising approach to latency reversal—in combination with appropriate tools for systemic clearance of persistent HIV infection—greatly increases opportunities for HIV eradication

Safety and efficacy of the NVX-CoV2373 coronavirus disease 2019 vaccine at completion of the placebo-controlled phase of a randomized controlled trial

Background: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. Methods: Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. Results: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. Conclusions: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated

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

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

Reconnaissance composition of river sand from northern South Island, New Zealand: a modern analogue for southern Taranaki Basin

The composition of 20 modern sand samples (18 streams, one beach, and one lakeshore) collected from the northern South Island provide a dataset for assessing detrital signatures of Paleozoic-Mesozoic basement terranes that may have served as sediment sources for reservoir sandstones in the Taranaki Basin. Non-plutonic terranes produce lithic-rich sand dominated by metamorphic fragments. Samples derived from erosion of the Rakaia and Caples terranes are more quartz-rich than the other non-plutonic terrane samples. Sand from the Dun Mountain-Maitai and Brook Street terranes has the lowest quartz content and is further distinguished by detrital serpentine. Pervasive pumpellyite-bearing metamorphic lithic fragments characterise the Caples, Dun Mountain-Maitai and Brook Street terranes. Feldspar is rare in Eastern province terrane sand. Sand from the Median Batholith tends to have less quartz than sand from the Karamea Batholith and a higher percentage of plagioclase, while sand from the Karamea Batholith has a higher proportion of potassium feldspar. Petrographic analyses were compared with published reports describing the composition of offshore sandstone reservoirs to evaluate their likely provenance

Sequence stratigraphy of the ANDRILL AND-2A drillcore, Antarctica: A long-term, ice-proximal record of Early to Mid-Miocene climate, sea-level and glacial dynamism

Present understanding of Antarctic climate change during the Early to Mid-Miocene, including major cycles of glacial expansion and contraction, relies in large part on stable isotope proxies from deep sea core drilling. Here, we summarize the lithostratigraphy of the ANDRILL Southern McMurdo Sound Project drillcore AND-2A. This core offers a hitherto unavailable ice-proximal stratigraphic archive from a high-accommodation continental margin setting, and provides clear evidence of repeated fluctuations in climate, ice expansion/contraction and attendant sea-level change over the period c. 20.2–14.2 Ma, with a more fragmentary record of Late Miocene and Pliocene time. The core is divided into seventy-four high-frequency (fourth- or fifth-order) glacimarine sequences recording repeated advances and retreats of glaciers into and out of the Victoria Land Basin. The section can be resolved into thirteen longer-term, composite (thirdorder) sequences, which comprise packages of higher frequency sequences that show a consistent stratigraphic stacking pattern (Stratigraphic Motif). The distribution of the six recognized motifs indicates intervals of less and more ice-proximal, and temperate to subpolar/polar climate, through the Miocene period. The core demonstrates a dynamic climate regime throughout the Early to Mid-Miocene that may be correlated to some previously-recognized events such as the Mid-Miocene Climatic Optimum, and provides a detailed reference point from which to evaluate stable isotope proxy records from the deep-sea