Human settlement of East Polynesia earlier, incremental, and coincident with prolonged South Pacific drought

The timing of human colonization of East Polynesia, a vast area lying between Hawai‘i, Rapa Nui, and New Zealand, is much debated and the underlying causes of this great migration have been enigmatic. Our study generates evidence for human dispersal into eastern Polynesia from islands to the west from around AD 900 and contemporaneous paleoclimate data from the likely source region. Lake cores from Atiu, Southern Cook Islands (SCIs) register evidence of pig and/or human occupation on a virgin landscape at this time, followed by changes in lake carbon around AD 1000 and significant anthropogenic disturbance from c. AD 1100. The broader paleoclimate context of these early voyages of exploration are derived from the Atiu lake core and complemented by additional lake cores from Samoa (directly west) and Vanuatu (southwest) and published hydroclimate proxies from the Society Islands (northeast) and Kiribati (north). Algal lipid and leaf wax biomarkers allow for comparisons of changing hydroclimate conditions across the region before, during, and after human arrival in the SCIs. The evidence indicates a prolonged drought in the likely western source region for these colonists, lasting c. 200 to 400 y, contemporaneous with the phasing of human dispersal into the Pacific. We propose that drying climate, coupled with documented social pressures and societal developments, instigated initial eastward exploration, resulting in SCI landfall(s) and return voyaging, with colonization a century or two later. This incremental settlement process likely involved the accumulation of critical maritime knowledge over several generations

Glacial-interglacial changes in central tropical Pacific surface seawater property gradients

Much uncertainty exists about the state of the oceanic and atmospheric circulation in the tropical Pacific over the last glacial cycle. Studies have been hampered by the fact that sediment cores suitable for study were concentrated in the western and eastern parts of the tropical Pacific, with little information from the central tropical Pacific. Here we present information from a suite of sediment cores collected from the Line Islands Ridge in the central tropical Pacific, which show sedimentation rates and stratigraphies suitable for paleoceanographic investigations. Based on the radiocarbon and oxygen isotope measurements on the planktonic foraminifera Globigerinoides ruber, we construct preliminary age models for selected cores and show that the gradient in the oxygen isotope ratio of G. ruber between the equator and 8°N is enhanced during glacial stages relative to interglacial stages. This stronger gradient could reflect enhanced equatorial cooling (perhaps reflecting a stronger Walker circulation) or an enhanced salinity gradient (perhaps reflecting increased rainfall in the central tropical Pacific).This is the publisher’s final pdf. The article is copyrighted by American Geophysical Union and published by John Wiley & Sons Ltd. It can be found at: http://agupubs.onlinelibrary.wiley.com/agu/journal/10.1002/%28ISSN%291944-9186/Keywords: tropical Pacific, oxygen isotopes, foraminifer

Increased Secreted Amyloid Precursor Protein-α (sAPPα) in Severe Autism: Proposal of a Specific, Anabolic Pathway and Putative Biomarker

Autism is a neurodevelopmental disorder characterized by deficits in verbal communication, social interactions, and the presence of repetitive, stereotyped and compulsive behaviors. Excessive early brain growth is found commonly in some patients and may contribute to disease phenotype. Reports of increased levels of brain-derived neurotrophic factor (BDNF) and other neurotrophic-like factors in autistic neonates suggest that enhanced anabolic activity in CNS mediates this overgrowth effect. We have shown previously that in a subset of patients with severe autism and aggression, plasma levels of the secreted amyloid-β (Aβ) precursor protein-alpha form (sAPPα) were significantly elevated relative to controls and patients with mild-to-moderate autism. Here we further tested the hypothesis that levels of sAPPα and sAPPβ (proteolytic cleavage products of APP by α- and β-secretase, respectively) are deranged in autism and may contribute to an anabolic environment leading to brain overgrowth. We measured plasma levels of sAPPα, sAPPβ, Aβ peptides and BDNF by corresponding ELISA in a well characterized set of subjects. We included for analysis 18 control, 6 mild-to-moderate, and 15 severely autistic patient plasma samples. We have observed that sAPPα levels are increased and BDNF levels decreased in the plasma of patients with severe autism as compared to controls. Further, we show that Aβ1-40, Aβ1-42, and sAPPβ levels are significantly decreased in the plasma of patients with severe autism. These findings do not extend to patients with mild-to-moderate autism, providing a biochemical correlate of phenotypic severity. Taken together, this study provides evidence that sAPPα levels are generally elevated in severe autism and suggests that these patients may have aberrant non-amyloidogenic processing of APP

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Suspended particles from ship’s surface intake samples collected on R/V Kilo Moana cruise KM1910 in June 2019

Dataset: Suspended particlesSurface particulate carbon concentration, nitrogen concentration, and bulk isotope composition (C and N) from underway clean water intake during June 2019 at station ALOHA during cruise KM1910. Suspended particulates were collected while underway using the ship's clean surface water intake ( ~0 to 5 m ocean depth) in the hydro lab sink aboard RV Kilo Moana. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/852242NSF Division of Ocean Sciences (NSF OCE) OCE-1911831, NSF Division of Ocean Sciences (NSF OCE) OCE-191199

Particulate phosphate, particulate carbon, particulate nitrogen, particulate bulk isotope composition (C and N), and dissolved oxygen from Niskin bottle samples collected on R/V Kilo Moana cruise KM1910 in June 2019

Dataset: Niskin bottle samplesParticulate phosphate, particulate carbon, particulate nitrogen, particulate bulk isotope composition (C and N), and dissolved oxygen, collected with Niskin bottles during CTD deployments in June 2019 at station ALOHA during cruise KM1910. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/852179NSF Division of Ocean Sciences (NSF OCE) OCE-1911831, NSF Division of Ocean Sciences (NSF OCE) OCE-191199

Increasing the usability of climate science in political decision-making

Abstract As climate-science graduate students at the University of Washington, we had the opportunity to engage in a political process focused on implementing legislation to reduce greenhouse gas emissions in Washington State. Our insights gained from this rare, first-hand, experience may be particularly relevant to other climate scientists. We argue that inflexible research goals within the United States climate-science community limit the relevance of the knowledge our community creates. The mismatch between climate-science research and the information needs of policy makers, while widely acknowledged in certain domains, has yet to be fully appreciated within many earth science disciplines. Broadening the climate-science training of graduate students to include education on the uses of climate information outside of academic settings would both inform and motivate new research directions, and engender validation of non-traditional research within disciplinary cultures

An Arctic Ocean paleosalinity proxy from d2H of palmitic acid provides evidence for deglacial Mackenzie River flood events

The hydrogen isotopic composition (2H/1H, or d2H) of palmitic acid (PA) was measured in surface sediments from the Laptev and Kara Seas in the Russian Arctic to evaluate its use as a paleohydrographic proxy. d2HPA values in surface sediments varied by 118‰ over a 21 ppt range in mean annual surface salinity, and the two properties were highly correlated (R2 ¼ 0.8, p < 0.001) according to the relationship d2HPA ¼ 4.22 (±0.60)*S - 338 (±15). In contrast, d2H values of vascular plant wax n-alkanes (nC27, nC29, nC31) did not change systematically with salinity. These differing lipid d2H trends support the interpretation of PA as derived primarily from marine microalgae at these sites. Both the range and absolute values of d2HPA compared favorably to those predicted from published Arctic Ocean salinity and water isotope data and the expected response of d2HPA to salinity in cultured phytoplankton. Some 64e74% of the observed sedimentary d2HPA increase is estimated to have resulted from increasing d2Hwater values, with the remainder resulting from decreased 2H-discrimination during lipid biosynthesis at higher salinities. The large signal and high sensitivity of d2HPA to surface salinity changes in the Russian Arctic was exploited to test the hypothesis that floodwaters emanated from the Mackenzie River during the late deglacial period. Measurements of d2HPA were performed in a sediment core from the continental slope off the Mackenzie River in the Canadian Arctic. In samples from the top Bølling/Allerød-Younger Dryas period, reconstructed surface salinities (and d2HPA values) off the Mackenzie River declined from 20 ("253‰) to 16 ("269‰) before rebounding to 24 ("236‰) in the early Holocene, close to the modern value of ~25. A large salinity depression in the Canadian Arctic just prior to the start of the Younger Dryas would support the hypothesis of a northern routing of flood-waters from glacial Lake Agassiz via the Mackenzie River as a trigger for the Younger Dryas event

Sinking particle from R/V Kilo Moana cruise KM1910 in June 2019

Dataset: Sinking particles from trapsPhosphorus, carbon (total and organic), and nitrogen flux and bulk isotope composition (C and N) from 3-day pit trap deployments in June 2019 at station ALOHA during cruise KM1910. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/852779NSF Division of Ocean Sciences (NSF OCE) OCE-1911831, NSF Division of Ocean Sciences (NSF OCE) OCE-191199