Stratigraphy and palaeoceanography of upper Maastrichtian chalks, southern Danish Central Graben

Upper Maastrichtian chalks form important hydrocarbon reservoirs in the Danish sector of the North Sea and have been intensively studied, yet their lithological uniformity can frustrate attempts to develop a high-resolution stratigraphic subdivision and a genetic understanding of the factors controlling production and sedimentation of the pelagic carbonate ooze. Recent research into these topics, supported by the Danish Energy Authority, was carried out by the Geological Survey of Denmark and Greenland (GEUS) in collaboration with the Geological Institute, University of Copenhagen by means of a multidisciplinary study involvingquantitative/semiquantitative palynology, micropalaeontology (nannofossils, foraminifers) and isotope geochemistry, integrated with detailed sedimentology. Two key wells were selected, the M-10X well from the Dan Field and the E-5X well from the Tyra SE Field (Fig. 1), based on the extensive core coverage in these wells and on their position in the southern part of the Danish Central Graben where evidence of large-scale resedimentation (and consequent stratigraphic complexity) is uncommon within the Maastrichtian section. In focusing on such a pelagic carbonate system, the ultimate aim is a holistic understanding of the marine system including temperature variation, nutrient supply and distribution, salinity, watermass layering, circulation and oxygen distribution. All these factors influence organic productivity and thus the accumulation of biogenic sediment. This study concentrated on a number of palaeoceanographic signals that can be derived from the sedimentary record, summarised in Fig. 2. Planktonic organisms, both phytoplankton (e.g. coccolithophores, some dinoflagellates) and zooplankton (e.g. foraminifers) provide a record of conditions in the upper water masses, largely within the photic zone, while bottom conditions are indicated by epifaunal/infaunal organisms (e.g. benthic foraminifers) and bioturbation, and by the sedimentological evidence of depositional processes at the sea floor. On a larger scale, the input of terrestrial organic material relative to the marine component can provide an indirect measure of shoreline migration and thus relative sea-level change, a factor that is also reflected in the δ13C isotopic composition of the seawater, as recorded by the biogenic carbonate ooze

A Census of Baryons and Dark Matter in an Isolated, Milky Way-sized Elliptical Galaxy

We present a study of the dark and luminous matter in the isolated elliptical galaxy NGC720, based on deep X-ray observations made with Chandra and Suzaku. The gas is reliably measured to ~R2500, allowing us to place good constraints on the enclosed mass and baryon fraction (fb) within this radius (M2500=1.6e12+/-0.2e12 Msun, fb(2500)=0.10+/-0.01; systematic errors are <~20%). The data indicate that the hot gas is close to hydrostatic, which is supported by good agreement with a kinematical analysis of the dwarf satellite galaxies. We confirm a dark matter (DM) halo at ~20-sigma. Assuming an NFW DM profile, our physical model for the gas distribution enables us to obtain meaningful constraints at scales larger than R2500, revealing that most of the baryons are in the hot gas. We find that fb within Rvir is consistent with the Cosmological value, confirming theoretical predictions that a ~Milky Way-mass (Mvir=3.1e12+/-0.4e12 Msun) galaxy can sustain a massive, quasi-hydrostatic gas halo. While fb is higher than the cold baryon fraction typically measured in similar-mass spiral galaxies, both the gas fraction (fg) and fb in NGC720 are consistent with an extrapolation of the trends with mass seen in massive galaxy groups and clusters. After correcting for fg, the entropy profile is close to the self-similar prediction of gravitational structure formation simulations, as observed in galaxy clusters. Finally, we find a strong heavy metal abundance gradient in the ISM similar to those observed in massive galaxy groups.Comment: 23 pages, 13 figures, 4 tables. Accepted for publication in the Astrophysical Journal. Minor modifications to match accepted version. Conclusions unchange

Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1 alpha axis

Abstract Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and double-stranded DNA breaks (SSBs and DSBs), and single-stranded gaps can block progression of the DNA replication fork, causing replicative stress and/or cell cycle arrest. However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to bypass some DNA lesions, which can circumvent the process leading to replication fork arrest and minimize replicative stress. Here, we show that Rev1-deficiency in mouse embryo fibroblasts or mouse liver tissue is associated with replicative stress and mitochondrial dysfunction. In addition, Rev1-deficiency is associated with high poly(ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD+, low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via the PARP-NAD+-SIRT1-PGC1α axis

Controlled Experiments of Hillslope Coevolution at the Biosphere 2 Landscape Evolution Observatory: Toward Prediction of Coupled Hydrological, Biogeochemical, and Ecological Change

Understanding the process interactions and feedbacks among water, porous geological media, microbes, and vascular plants is crucial for improving predictions of the response of Earth’s critical zone to future climatic conditions. However, the integrated coevolution of landscapes under change is notoriously difficult to investigate. Laboratory studies are limited in spatial and temporal scale, while field studies lack observational density and control. To bridge the gap between controlled laboratory and uncontrollable field studies, the University of Arizona built a macrocosm experiment of unprecedented scale: the Landscape Evolution Observatory (LEO). LEO comprises three replicated, heavily instrumented, hillslope-scale model landscapes within the environmentally controlled Biosphere 2 facility. The model landscapes were designed to initially be simple and purely abiotic, enabling scientists to observe each step in the landscapes’ evolution as they undergo physical, chemical, and biological changes over many years. This chapter describes the model systems and associated research facilities and illustrates how LEO allows for tracking of multiscale matter and energy fluxes at a level of detail impossible in field experiments. Initial sensor, sampler, and soil coring data are already providing insights into the tight linkages between water flow, weathering, and microbial community development. These interacting processes are anticipated to drive the model systems to increasingly complex states and will be impacted by the introduction of vascular plants and changes in climatic regimes over the years to come. By intensively monitoring the evolutionary trajectory, integrating data with mathematical models, and fostering community-wide collaborations, we envision that emergent landscape structures and functions can be linked, and significant progress can be made toward predicting the coupled hydro-biogeochemical and ecological responses to global change

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P\u3c0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.

Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia:Recent Progress on the Mechanisms and Interventional Strategies

Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.</p

Acute intestinal failure: international multicenter point-of-prevalence study

Background & aims: Intestinal failure (IF) is defined from a requirement or intravenous supplementation due to failing capacity to absorb nutrients and fluids. Acute IF is an acute, potentially reversible form of IF. We aimed to identify the prevalence, underlying causes and outcomes of acute IF. Methods: This point-of-prevalence study included all adult patients hospitalized in acute care hospitals and receiving parenteral nutrition (PN) on a study day. The reason for PN and the mechanism of IF (if present) were documented by local investigators and reviewed by an expert panel. Results: Twenty-three hospitals (19 university, 4 regional) with a total capacity of 16,356 acute care beds and 1237 intensive care unit (ICU) beds participated in this study. On the study day, 338 patients received PN (21 patients/1000 acute care beds) and 206 (13/1000) were categorized as acute IF. The categorization of reason for PN was revised in 64 cases (18.9% of total) in consensus between the expert panel and investigators. Hospital mortality of all study patients was 21.5%; the median hospital stay was 36 days. Patients with acute IF had a hospital mortality of 20.5% and median hospital stay of 38 days (P > 0.05 for both outcomes). Disordered gut motility (e.g. ileus) was the most common mechanism of acute IF, and 71.5% of patients with acute IF had undergone abdominal surgery. Duration of PN of ≥42 days was identified as being the best cut-off predicting hospital mortality within 90 days. PN ≥ 42 days, age, sepsis and ICU admission were independently associated with 90-day hospital mortality. Conclusions: Around 2% of adult patients in acute care hospitals received PN, 60% of them due to acute IF. High 90-day hospital mortality and long hospital stay were observed in patients receiving PN, whereas presence of acute IF did not additionally influence these outcomes. Duration of PN was associated with increased 90-day hospital mortality

Effects of semaglutide on symptoms, function, and quality of life in patients with heart failure with preserved ejection fraction and obesity: a prespecified analysis of the STEP-HFpEF trial

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [–0.6 to 9.9] points; for body weight, –11 [–13.2 to –8.8], –9.4 [–11.5 to –7.2], and –11.8 [–14.0 to –9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction&gt;0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7–9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6–2.9 across domains; P&lt;0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains