Understanding Extraneous Argon in Silicic Volcanic Products Using ⁴⁰Ar/³⁹Ar Laserprobe Geochronology

The Ar-Ar dating technique is one of the most widely applied geochronological techniques to products of silicic volcanism, which represent geologically instantaneous events, and have been used to calibrate the geological timescale, correlate stratigraphy and biostratigraphy over large areas, and assess the impact of explosive volcanic eruptions. Recent advances (e.g., improved instrument precision and recalibration of the K-Ar decay scheme), are now making it possible to obtain increasingly precise and accurate ages for young volcanic eruptions, K-poor minerals, and even discrete parts of single crystals. These advances have highlighted the realisation that relatively small levels of Ar contamination (e.g., extraneous Ar, either excess (40ArE), or inherited Ar), previously assumed to be minor, may now have a considerable effect on the accuracy of ages determined using the Ar-Ar technique. To assess the issue of extraneous Ar, this study applied the Ar-Ar technique to a range of minerals (including sanidine, plagioclase and biotite), and glass separated from the products of large-volume silicic magma systems, which have undergone repeated cycles of crystallisation and rejuvenation. The in situ Ar-Ar laserprobe technique was applied to dacite of the Fish Canyon magmatic system (erupted at ~28 Ma; Colorado, USA), and the single-grain fusion Ar-Ar laser melting technique was applied to rhyolitic pumice (from explosive ignimbrite and ash fall, and effusive dome building events) of the Yellowstone Plateau Volcanic Field (< 2.1 Ma; Idaho, Wyoming, USA), and the Bishop Tuff (erupted at -0.76 Ma; California, USA). The in situ study revealed variable 40ArE contamination of feldspar (i.e., hosted in fluid and melt inclusions in plagioclase and sanidine), and biotite (incorporated 40ArE due to having a relatively high Ar mineral/fluid partition coefficient), resulting in an age range of 25.07±1.86 to 61.46±10.11 Ma. Single-grain fusion experiments revealed that in some cases the source of extraneous Ar was identifiable as partially re-set xenocrysts contaminating systems immediately prior to, and/or during eruption. In other cases, in particular some Yellowstone rhyolite domes, persistent recycling of material (crystal mixes including phenocrysts and antecrysts imparting an inherited Ar component), has resulted in a spread to older ages. This signal of inheritance is also seen in U-Pb zircon ages, but this is less evident or absent in Ar-Ar ages of co-existing glass. Ar diffusion modelling and Ar-Ar data in this study suggests sanidine is more likely to yield an eruption age. The use of sanidine feldspar, instead of anorthoclase and/or plagioclase feldspar is therefore strongly recommended. Biotite, which has shown to incorporate the largest proportion of 40ArE, should be used with caution, and successful dating of a glass phase can be a useful geochronological tool. Despite extraneous Ar contamination, the Ar-Ar dating technique can be successfully applied to the products of silicic volcanism. This work has provided the opportunity to determine new Ar-Ar eruption ages (Green Canyon Flow dome at 1.29±0.01 Ma; Sheridan Reservoir dome at 2.04±0.03 Ma, and Snake River Butte dome at 2.15±0.01 Ma), for rhyolite domes of the Yellowstone Plateau Volcanic Field previously only dated using the K-Ar technique. Finally, dating multiple phases (e.g., feldspar (sanidine); glass, and where possible zircon) is strongly recommended in order to identify cases of subtle contamination which will have a negative impact on our ability to obtain an accurate eruption age

Observation of centimetre-scale argon diffusion in alkali feldspars: implications for ⁴⁰Ar/³⁹Ar thermochronology

New data from a gem-quality feldspar from Itrongay, Madagascar, record naturally occurring 40Ar/39Ar age profiles which can be numerically modelled by invoking a single diffusion mechanism and show that microtexturally simple crystals are capable of recording complex thermal histories. We present the longest directly measured, naturally produced 40Ar*-closure profiles from a single, homogeneous orthoclase feldspar. These data appear to confirm the assumption that laboratory derived diffusion parameters are valid in nature and over geological timescales. Diffusion domains are defined by crystal faces and ancient cracks, thus in gem-quality feldspars the diffusion domain size equates to the physical grain size. The data also illustrate the potential of large, gem-quality feldspars to record detailed thermal histories over tens of millions of years and such samples should be considered for future studies on the slow cooling of continental crust

Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer

High-grade serous ovarian carcinoma (HGSOC) is a cancer with dismal prognosis due to the limited effectiveness of existing chemo- and immunotherapies. To elucidate mechanisms mediating sensitivity or resistance to these therapies, we developed a fast and flexible autochthonous mouse model based on somatic introduction of HGSOC-associated genetic alterations into the ovary of immunocompetent mice using tissue electroporation. Tumors arising in these mice recapitulate the metastatic patterns and histological, molecular, and treatment response features of the human disease. By leveraging these models, we show that the ability to undergo senescence underlies the clinically observed increase in sensitivity of homologous recombination (HR)-deficient HGSOC tumors to platinum-based chemotherapy. Further, cGas/STING-mediated activation of a restricted senescence-associated secretory phenotype (SASP) was sufficient to induce immune infiltration and sensitize HR-deficient tumors to immune checkpoint blockade. In sum, our study identifies senescence propensity as a predictor of therapy response and defines a limited SASP profile that appears sufficient to confer added vulnerability to concurrent immunotherapy and, more broadly, provides a blueprint for the implementation of electroporation-based mouse models to reveal mechanisms of oncogenesis and therapy response in HGSOC

Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily). METHODS: This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as "definite," "probable," or "possible" using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40. DISCUSSION: The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT04145258. Registered on October 30, 2019

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.Peer reviewe

Electroweak production of two jets in association with a Z boson in proton-proton collisions root s =13 TeV

A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 <cwww/Lambda(2) <2.6 TeV-2 and -8.4 <cw/Lambda(2) <10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.Peer reviewe

Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s}$ = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s}$ = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s} =$ 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s} =$ 7 TeV, as well as with theoretical predictions

Measurement of electroweak WZ boson production and search for new physics in WZ + two jets events in pp collisions at √s=13TeV

A measurement of WZ electroweak (EW) vector boson scattering is presented. The measurement is performed in the leptonic decay modes WZ→ℓνℓ′ℓ′, where ℓ,ℓ′=e,μ. The analysis is based on a data sample of proton-proton collisions at √s=13 TeV at the LHC collected with the CMS detector and corresponding to an integrated luminosity of 35.9 fb−1. The WZ plus two jet production cross section is measured in fiducial regions with enhanced contributions from EW production and found to be consistent with standard model predictions. The EW WZ production in association with two jets is measured with an observed (expected) significance of 2.2 (2.5) standard deviations. Constraints on charged Higgs boson production and on anomalous quartic gauge couplings in terms of dimension-eight effective field theory operators are also presented