Assessment of C, N, and Si Isotopes as Tracers of Past Ocean Nutrient and Carbon Cycling

28 pages, 6 figures, 1 box, 1 appendix.-- Data Availability Statement: Data sets presented in this research are available via the following repositories and study (listed by Figure): Figures 3 and 4: (1)δ13CDIC:(a) CLIVAR P16S (Feely et al., 2008) from GLODAPv2.2020 database (Olsen et al., 2020): https://www.glodap.info/index.php/merged-and-adjusted-data-product/. (b) GEOTRACES GA03 (Quay & Wu, 2015) and GP16 (P. Quay, unpublished data) from GEOTRACES IDP2017 (Schlitzer et al., 2018): https://www.bodc.ac.uk/geotraces/data/idp2017/. (2) δ15Nnitrate:(a) CLIVAR P16S (Rafter et al., 2013) from BCO-DMO: https://www.bco-dmo.org/dataset/651722. (b) GEOTRACES GA03 (Marconi et al., 2015) and GP16 (Peters et al., 2018) from GEOTRACES IDP2017 (Schlitzer et al., 2018): https://www.bodc.ac.uk/geotraces/data/idp2017/. (3) δ30Si: GEOTRACES GA03 (Brzezinski & Jones, 2015) and GIPY04 (Fripiat et al., 2012) from GEOTRACES IDP2017 (Schlitzer et al., 2018): https://www.bodc.ac.uk/geotraces/data/idp2017/. (4) Figure 4a POC Flux (DeVries & Weber, 2017): SIMPLE-TRIM Output from https://tdevries.eri.ucsb.edu/models-and-data-products/. Figure 5: (a) Antarctic CO2 composite: https://www.ncdc.noaa.gov/paleo-search/study/17975. (b) ∆δ13Cthermocline-deep from Ziegler et al. (2013) supporting information: https://www.nature.com/articles/ngeo1782; ∆δ13Cepifaunal-infaunal (Hoogakker et al., 2018): https://doi.pangaea.de/10.1594/PANGAEA.891185. (c) SAZ FB-δ15N (Martínez-García et al., 2014): https://www.ncdc.noaa.gov/paleo/study/18318; AZ DB-δ15N (Studer et al., 2015): https://doi.pangaea.de/10.1594/PANGAEA.848271. (d) SAZ Fe flux (Martínez-García et al., 2014): https://www.ncdc.noaa.gov/paleo/study/18318. (e) AZ diatom δ30Si (Robinson et al., 2014): https:// www.ncdc.noaa.gov/paleo/study/17917. Figure 6: (a) and (b) Benthic foraminifera δ18O and δ13C (Zachos et al., 2001): https:// www.ncdc.noaa.gov/paleo/study/8674. (c) FB-δ15N from Kast et al. (2019) supporting information data: https://science.sciencemag.org/content/suppl/2019/04/24/364.6438.386.DC1. (d) and (e) Diatom, sponge, and radiolarian δ30Si in Egan et al. (2013) supporting information: https://www.sciencedirect.com/science/article/pii/S0012821X13002185, Fontorbe et al. (2016) supporting information: https://www.sciencedirect.com/science/article/pii/S0012821X16304265, and Fontorbe et al. (2017) supporting information: https://agupubs.onlinelibrary.wiley.com/doi/full/10.1002/2017PA003090Biological productivity in the ocean directly influences the partitioning of carbon between the atmosphere and ocean interior. Through this carbon cycle feedback, changing ocean productivity has long been hypothesized as a key pathway for modulating past atmospheric carbon dioxide levels and hence global climate. Because phytoplankton preferentially assimilate the light isotopes of carbon and the major nutrients nitrate and silicic acid, stable isotopes of carbon (C), nitrogen (N), and silicon (Si) in seawater and marine sediments can inform on ocean carbon and nutrient cycling, and by extension the relationship with biological productivity and global climate. Here, we compile water column C, N, and Si stable isotopes from GEOTRACES-era data in four key ocean regions to review geochemical proxies of oceanic carbon and nutrient cycling based on the C, N, and Si isotopic composition of marine sediments. External sources and sinks as well as internal cycling (including assimilation, particulate matter export, and regeneration) are discussed as likely drivers of observed C, N, and Si isotope distributions in the ocean. The potential for C, N, and Si isotope measurements in sedimentary archives to record aspects of past ocean C and nutrient cycling is evaluated, along with key uncertainties and limitations associated with each proxy. Constraints on ocean C and nutrient cycling during late Quaternary glacial-interglacial cycles and over the Cenozoic are examined. This review highlights opportunities for future research using multielement stable isotope proxy applications and emphasizes the importance of such applications to reconstructing past changes in the oceans and climate systemThis workshop was funded by the United States National Science Foundation (NSF) through the GEOTRACES program, the international Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and NSF, and the French national program LEFE (Les Enveloppes Fluides et l'Environnement). [...] This study was supported by PAGES, LEFE, and GEOTRACES through NSF. J. R. Farmer acknowledges support from the Max Planck Society, the Tuttle Fund of the Department of Geosciences of Princeton University, the Grand Challenges Program of the Princeton Environmental Institute, and through Exxon Mobil via the Andlinger Center for Energy and the Environment of Princeton University. Open access funding enabled and organized by Projekt DEAL. [...] With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S

Scenario trees and policy selection for multistage stochastic programming using machine learning

We propose a hybrid algorithmic strategy for complex stochastic optimization problems, which combines the use of scenario trees from multistage stochastic programming with machine learning techniques for learning a policy in the form of a statistical model, in the context of constrained vector-valued decisions. Such a policy allows one to run out-of-sample simulations over a large number of independent scenarios, and obtain a signal on the quality of the approximation scheme used to solve the multistage stochastic program. We propose to apply this fast simulation technique to choose the best tree from a set of scenario trees. A solution scheme is introduced, where several scenario trees with random branching structure are solved in parallel, and where the tree from which the best policy for the true problem could be learned is ultimately retained. Numerical tests show that excellent trade-offs can be achieved between run times and solution quality

A review of the stable isotope bio-geochemistry of the global silicon cycle and its associated trace elements

Silicon (Si) is the second most abundant element in the Earth's crust and is an important nutrient in the ocean. The global Si cycle plays a critical role in regulating primary productivity and carbon cycling on the continents and in the oceans. Development of the analytical tools used to study the sources, sinks, and fluxes of the global Si cycle (e.g., elemental and stable isotope ratio data for Ge, Si, Zn, etc.) have recently led to major advances in our understanding of the mechanisms and processes that constrain the cycling of Si in the modern environment and in the past. Here, we provide background on the geochemical tools that are available for studying the Si cycle and highlight our current understanding of the marine, freshwater and terrestrial systems. We place emphasis on the geochemistry (e.g., Al/Si, Ge/Si, Zn/Si, δ13C, δ15N, δ18O, δ30Si) of dissolved and biogenic Si, present case studies, such as the Silicic Acid Leakage Hypothesis, and discuss challenges associated with the development of these environmental proxies for the global Si cycle. We also discuss how each system within the global Si cycle might change over time (i.e., sources, sinks, and processes) and the potential technical and conceptual limitations that need to be considered for future studies.The work by JS was supported by the “Laboratoire d’Excellence” LabexMER (ANR-10-LABX-19) and co-funded by a grant from the French government under the program “Investissements d’Avenir,” and by a grant from the Regional Council of Brittany (SAD programme). DJC was partially supported by the Knut and Alice Wallenberg Foundation (KAW Wallenberg Scholar) and the Swedish Research Council. This review article has benefited from funding by the European Union Seventh Framework Programme under grant agreement n◦294146 (project MuSiCC, Marie Curie CIG to DC). GdS is supported by a Marie Skłodowska-Curie Research Fellowship under EU Horizon2020 (GA #708407). JuD was supported by the American Chemical Society Petroleum Research Fund (Grant # 53798-DNI2). CE acknowledges financial support by the Institute for Chemistry and Biology of the Marine Environment (Oldenburg, Germany) and the Max Planck Institute for Marine Microbiology (Bremen, Germany). KH is funded by The Royal Society (UF120084) and the European Research Council (ERC-2015-StG - 678371_ICY-LAB). PG acknowledges funding by the Collaborative Research Centre 754 “ClimateBiogeochemistry interactions in the Tropical Ocean” (www. sfb754.de), supported by the Deutsche Forschungsgemeinschaft (DFG)

A national cross-sectional study among drug-users in France: epidemiology of HCV and highlight on practical and statistical aspects of the design

<p>Abstract</p> <p>Background</p> <p>Epidemiology of HCV infection among drug users (DUs) has been widely studied. Prevalence and sociobehavioural data among DUs are therefore available in most countries but no study has taken into account in the sampling weights one important aspect of the way of life of DUs, namely that they can use one or more specialized services during the study period. In 2004–2005, we conducted a national seroepidemiologic survey of DUs, based on a random sampling design using the Generalised Weight Share Method (GWSM) and on blood testing.</p> <p>Methods</p> <p>A cross-sectional multicenter survey was done among DUs having injected or snorted drugs at least once in their life. We conducted a two stage random survey of DUs selected to represent the diversity of drug use. The fact that DUs can use more than one structure during the study period has an impact on their inclusion probabilities. To calculate a correct sampling weight, we used the GWSM. A sociobehavioral questionnaire was administered by interviewers. Selected DUs were asked to self-collect a fingerprick blood sample on blotting paper.</p> <p>Results</p> <p>Of all DUs selected, 1462 (75%) accepted to participate. HCV seroprevalence was 59.8% [95% CI: 50.7–68.3]. Of DUs under 30 years, 28% were HCV seropositive. Of HCV-infected DUs, 27% were unaware of their status. In the month prior to interview, 13% of DUs shared a syringe, 38% other injection parapharnelia and 81% shared a crack pipe. In multivariate analysis, factors independently associated with HCV seropositivity were age over 30, HIV seropositivity, having ever injected drugs, opiate substitution treatment (OST), crack use, and precarious housing.</p> <p>Conclusion</p> <p>This is the first time that blood testing combined to GWSM is applied to a DUs population, which improve the estimate of HCV prevalence. HCV seroprevalence is high, indeed by the youngest DUs. And a large proportion of DUs are not aware of their status. Our multivariate analysis identifies risk factors such as crack consumption and unstable housing.</p

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

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

Batch mode reinforcement learning based on the synthesis of artificial trajectories

In this paper, we consider the batch mode reinforcement learning setting, where the central problem is to learn from a sample of trajectories a policy that satisfies or optimizes a performance criterion. We focus on the continuous state space case for which usual resolution schemes rely on function approximators either to represent the underlying control problem or to represent its value function. As an alternative to the use of function approximators, we rely on the synthesis of “artificial trajectories” from the given sample of trajectories, and show that this idea opens new avenues for designing and analyzing algorithms for batch mode reinforcement learning

Bioactive trace metals and their isotopes as paleoproductivity proxies: An assessment using GEOTRACES-era data

International audiencePhytoplankton productivity and export sequester climatically significant quantities of atmospheric carbon dioxide as particulate organic carbon through a suite of processes termed the biological pump. How the biological pump operated in the past is therefore important for understanding past atmospheric carbon pump requires proxies. Due to their intimate association with biological processes, several bioactive trace metals and their isotopes are potential proxies for past phytoplankton productivity, including: iron, zinc, copper, cadmium, molybdenum, barium, nickel, chromium, and silver. Here we review the oceanic distributions, driving processes, and depositional archives for these nine metals and their isotopes based on GEOTRACES-era datasets. We offer an assessment of the overall maturity of each isotope system to serve as a proxy for diagnosing aspects of past ocean productivity and identify priorities for future research. This assessment reveals that cadmium, barium, nickel, and chromium isotopes offer the most promise as tracers of paleoproductivity, whereas iron, zinc, copper, and molybdenum do not. Too little is known about silver to make a confident determination. Intriguingly, the elements that are least sensitive to productivity may be used to trace other aspects of ocean chemistry, such as nutrient sources, particle scavenging, organic complexation, and ocean redox state. These complementary sensitivities suggest new opportunities for combining perspectives from multiple proxies that will ultimately enable painting a more complete picture of marine paleoproductivity, biogeochemical cycles, and Earth's climate history