The QCD axion is a leading dark matter candidate that emerges as part of the solution to the strong-CP problem in the Standard Model. The coupling of the axion to photons is the most common ...experimental probe, but much parameter space remains unexplored. The coupling of the QCD axion to the Standard Model scales linearly with the axion mass; therefore, the highly motivated region 0.4–120 neV, corresponding to a GUT-scale axion, is particularly difficult to reach. This paper presents the design requirements for a definitive search for GUT-scale axions and reviews the technological advances needed to enable this program.
The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, ...replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD.
We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units PFU, 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed.
The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months.
This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).
After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another.
...We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores).
Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events.
After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.).
Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We ...analysed two decades of bla
evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the bla
gene across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. We showed how an initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability of bla
to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, bla
persisted through diversification of genetic settings that resulted from transfer of bla
plasmids between bacterial hosts and of the integron carrying bla
between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.
The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This ...Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.
LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. ...Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10−48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5 σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020.
The LUX-ZEPLIN (LZ) experiment is a dark matter detector centered on a dual-phase xenon time projection chamber. We report searches for new physics appearing through few-keV-scale electron recoils, ...using the experiment’s first exposure of 60 live days and a fiducial mass of 5.5 t. The data are found to be
consistent with a background-only hypothesis, and limits are set on models for new physics including solar axion electron coupling, solar neutrino magnetic moment and millicharge, and electron couplings to galactic axionlike particles and hidden photons. Similar limits are set on weakly interacting massive
particle (WIMP) dark matter producing signals through ionized atomic states from the Migdal effect.
Many trace metals such as iron, copper, and manganese have lower concentrations in the surface waters of the North Pacific Ocean than in North Atlantic surface waters. However, cobalt and zinc ...concentrations in North Atlantic surface waters are often as low as those reported in the North Pacific. We studied the relationship between the distribution of cobalt, zinc, and phosphorus in surface waters of the western North Atlantic Ocean. Both metals show strong depletion in the southern Sargasso Sea, a region characterized by exceedingly low dissolved inorganic phosphorus (generally <4 nmol L−1) and measurable alkaline phosphatase activity. Alkaline phosphatase is a metalloenzyme (typically containing zinc) that cleaves phosphate monoesters and is a diagnostic indicator of phosphorus stress in phytoplankton. In contrast to the North Pacific Ocean, cobalt and zinc appear to be drawn down to their lowest values only when inorganic phosphorus is below 10 nmol L−1 in the North Atlantic Ocean. Lower levels of phosphorus in the Atlantic may contribute to these differences, possibly through an increased biological demand for zinc and cobalt associated with dissolved organic phosphorus acquisition. This hypothesis is consistent with results of a culture study where alkaline phosphatase activity decreased in the model coccolithophore Emiliania huxleyi upon zinc and cobalt limitation.
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