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A firm understanding of the relationship between atmospheric carbon dioxide concentration and temperature is critical for interpreting past climate change and for predicting future climate change. A recent synthesis suggests that the increase in global-mean surface temperature in response to a doubling of the atmospheric carbon dioxide concentration, termed ‘climate sensitivity’, is between 1.5 and 6.2 °C (5–95 per cent likelihood range), but some evidence is inconsistent with this range. Moreover, most estimates of climate sensitivity are based on records of climate change over the past few decades to thousands of years, when carbon dioxide concentrations and global temperatures were similar to or lower than today, so such calculations tend to underestimate the magnitude of large climate-change events and may not be applicable to climate change under warmer conditions in the future. Here we estimate long-term equilibrium climate sensitivity by modelling carbon dioxide concentrations over the past 420 million years and comparing our calculations with a proxy record. Our estimates are broadly consistent with estimates based on short-term climate records, and indicate that a weak radiative forcing by carbon dioxide is highly unlikely on multi-million-year timescales. We conclude that a climate sensitivity greater than 1.5 °C has probably been a robust feature of the Earth’s climate system over the past 420 million years, regardless of temporal scaling. [ABSTRACT FROM AUTHOR]

A reliable, non-invasive diagnostic method is needed for early detection and serial monitoring of cardiotoxicity, a well-known side effect of chemotherapy. This study aimed to assess the feasibility of T1-mapping cardiac magnetic resonance imaging (CMR) for evaluating subclinical myocardial changes in a doxorubicin-induced cardiotoxicity rabbit model. Adult male New Zealand White rabbits were injected twice-weekly with doxorubicin and subjected to CMR on a clinical 3T MR system before and every 2–4 weeks post-drug administration. Native T1 and extracellular volume (ECV) values were measured at six mid-left ventricle (LV) and specific LV lesions. Histological assessments evaluated myocardial injury and fibrosis. Three pre-model and 11 post-model animals were included. Myocardial injury was observed from 3 weeks. Mean LV myocardium ECV values increased significantly from week 3 before LV ejection fraction decreases (week 6), and ECVs of the RV upper/lower insertion sites and papillary muscle exceeded those of the LV. The mean native T1 value in the mid-LV increased significantly increased from week 6, and LV myocardium ECV correlated strongly with the degree of fibrosis (r = 0.979, p < 0.001). Myocardial T1 mapping, particularly ECV values, reliably and non-invasively detected early cardiotoxicity, allowing serial monitoring of chemotherapy-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Long-term carbon and sulfur cycle models have helped shape our understanding of the Phanerozoic history of atmospheric CO2 and O2, but error analyses have been largely limited to testing only a subset of input parameters singly. As a result, the full ranges of probable CO2 and O2 are not quantitatively known. Here we investigate how variation in all 68 input parameters of the GEOCARBSULF model, both singly and in combination, affect estimated CO2 and O2. We improve formulations for land area, runoff, and continental temperature, the latter of which now excludes land area not experiencing chemical weathering. We find our resampled model CO2 and O2 estimates are well bounded and provide high confidence for a "double-hump" in CO2 during the Phanerozoic, with high values during the early Paleozoic and Mesozoic, and low values during the late Paleozoic and late Mesozoic-to-Cenozoic. Our analyses also support a distinct atmospheric O2 peak during the late Paleozoic (>30%) followed by low values near the Triassic-Jurassic boundary (~10%). Most of the spread in CO2 is contributed by three factors: climate sensitivity to CO2-doubling and the plant-assisted chemical weathering factors LIFE and GYM. CO2 estimates during the Paleozoic to early Mesozoic are highly concordant with independent records from proxies, but are offset to lower values during the globally warm late Mesozoic to early Cenozoic. The model-proxy mismatch for the late Mesozoic can be eliminated with a change in GYM within its plausible range, but no change within plausible ranges can resolve the early Cenozoic mismatch. Either the true value for one or more input parameters during this interval is outside our sampled range, or the model is missing one or more key processes. [ABSTRACT FROM AUTHOR]

Abstract: Seismic anisotropy, a property linked to the texture of the mantle rock, should be distributed with depth along the trace of the Dead Sea Rift (DSR), owing to a combination of present day and ancient tectonics. Using data from four permanent and one temporary seismic observatories we evaluate birefringence (splitting) of 91 teleseismic core-refracted shear waves, primarily SKS phases. We find significant levels of birefringence in the bulk of observed phases. We also find that birefringence parameters (fast directions and delays) vary as a function of source–receiver geometry. Notably, the pattern of this directional variation in birefringence is quite similar at all sites we have examined. We interpret observed birefringence in SKS phases in terms of one- and two-layer models. Single-layer models for all stations exhibit a fast polarization oriented 12–19° east of north, with anisotropy sufficient to generate 1.3-s time delay. We find strong evidence for at least two distinct anisotropic layers. For the two layer models, the upper layers resemble the single-layer models, showing near-north fast polarizations and delays on the order of 1s. Three out of four sites show fast polarizations in the lower layer that strike 50–80° CW from north with time delays 0.3–0.6s. One site, at the northern end of the DSR, displays a higher degree of anisotropy in the lower layer, and a more northerly fast polarization. Overall, the lower layers at all sites appear to be consistent with the deformation caused by plate motion relative to the asthenosphere. The fabric in the upper layer is sub-parallel to the present-day transcurrent motion on the DSR, but also matches the typical orientation of lithospheric seismic anisotropy in the Arabian shield. Our overall conclusion is that the impact of the DSR on the rock fabric of the mantle lithosphere is probably quite weak. [Copyright &y& Elsevier]

Tomographic images of the distribution of shear-wave speed beneath the northwestern Pacific delineate the configuration of the subducted oceanic lithosphere beneath the western Aleutian arc. At ∼100 km depth, a fast shear-wave speed anomaly is beneath the Aleutian arc everywhere east of 173°E. Between 164°E and 173°E, however, seismic velocities at this depth are slow relative to the surrounding mantle. The lateral termination of the fast shear-wave speed anomaly at depth coincides with a gap in deep seismicity beneath the Aleutians. The absence of these two distinctive traits of subducting slabs leads us to conclude that this segment of the Aleutian arc overlies a very large window in the otherwise continuous lithospheric slab that we term a ‘slab portal.’ This portal is likely to facilitate the production of distinctive volcanic rocks (adakites or high-Mg# andesites) by partially melting the adjacent edges of the slab. The Miocene age of most adakites in the westernmost Aleutians where no slab is present may indicate that the portal formed relatively recently. The chemistry of western Aleutian adakites approximates that of typical continental crust, so their genesis and subsequent lateral transport toward Kamchatka is a plausible mechanism for new continent formation. [ABSTRACT FROM AUTHOR]

Presents images of the seismic structure beneath the Aleutian-Kamchatka junctions (AKJ) and the surrounding region. Geodynamics of the AKJ; Occurrence of two episodes of catastrophic slab loss; Tomographic imaging of the upper-mantle compressional velocity structure in the AKJ region with body waves.

This study presents observations of Love-to-Rayleigh scattering beneath the eastern North American passive margin that place new constraints on seismic anisotropy in the upper mantle. The scattering of Love-wave energy to Rayleigh waves is generated via sharp lateral gradients in anisotropic structure along the source-receiver path. The scattered phases, known as quasi-Love (QL) waves, exhibit amplitude behavior that depends on the strength of the anisotropic contrast as well as the geometrical relationship between the propagation azimuth and the anisotropic symmetry axis. Previous studies of seismic anisotropy in the upper mantle beneath eastern North America have revealed evidence for a mix of lithospheric and asthenospheric contributions, but the interpretation of indicators such as SKS splitting is hampered by a lack of vertical resolution. Complementary constraints on the depth distribution of anisotropy can be provided by surface waves, which have the additional advantage of sampling portions of the margin that lie offshore. Here we present measurements of QL phases using data from several hundred broadband seismic stations in eastern North America, including stations of the USArray Transportable Array, the Central and Eastern U.S. Network, and the MAGIC experiment in the central Appalachians. We find evidence for clear QL arrivals at stations in eastern North America, consistent with a region of particularly strong and coherent scattering inferred just offshore the central portion of the margin. The coherent scattering near the Eastern North American Margin likely reflects lateral transitions in seismic anisotropy in the asthenospheric mantle, associated with locally complex three-dimensional flow, with possible additional contributions from anisotropy in the mantle lithosphere. A second region of strong QL scattering near the southern coast of Greenland is enigmatic in origin, but may be due to pre-existing lithospheric fabric. • We observe Love-to-Rayleigh scattering at seismic stations in eastern North America. • There is coherent scattering offshore the Eastern North American Margin (ENAM). • A region of coherent scattering in and around southern Greenland is also observed. • Our observations indicate lateral variations in upper mantle seismic anisotropy. [ABSTRACT FROM AUTHOR]

Functional profiling of CFTR-directed therapeutics offers the potential to provide significant benefits to young people with cystic fibrosis (CF). However, the development of 2D airway epithelial cell models for individual response tests in CF children remains a central task. The objective of this study was to determine the utility of EpiX TM technology for expansion of nasal epithelial cells for use in electrophysiological CFTR function measurements. An initial harvest of as few as 20,000 cells was sufficient to expand up to 50 million cells that were used to generate air-liquid interface (ALI) cultures for ion transport studies with the Ussing assay. CFTR function was assessed by measuring responses to forskolin and the CFTR potentiator VX-770 (ivacaftor) in ALI cultures generated from passage 3 and 4 cells. Short-circuit current (Isc) measurements of blocked CFTR currents (ΔI CFTRinh ) discriminated CFTR function between healthy control (wild type, WT) and patients with intermediate (F508del/R117H-7T: 56% WT) and severe (F508del/F508del: 12% WT) CF disease. For the mixed genotypes, CFTR activity for F508del/c.850dupA was 12% WT, R334W/406-1G>A was 24% WT, and CFTRdele2,3(21 kb)/CFTRdele2,3(21 kb) was 9% WT. The CFTR correctors VX-809 (lumacaftor) and VX-661 (tezacaftor) significantly increased CFTR currents for F508del/R117H to 73 and 67% WT, respectively. Cultures with the large deletion mutation CFTRdele2,3(21 kb) unexpectedly responded to VX-661 treatment (20% WT). Amiloride-sensitive sodium currents were robust and ranged between 20-80 μA/cm 2 depending on the subject. In addition to characterizing the electrophysiological profile of mutant CFTR activity in cultures for five genotypes, our study exemplifies the promising paradigm of bed-to-bench side cooperation and personalized medicine., (Copyright © 2020 Park, Shrivastava, Zhang, Pollok, Finkbeiner, Gibb, Ly and Illek.)

Background: Transcatheter left atrial appendage occlusion (LAAO) using Watchman device has been demonstrated to be efficacious in decreasing stroke risk in patients with atrial fibrillation who are not suitable for long-term anticoagulation. Residual leaks are frequently encountered following LAAO procedures and their clinical implications and optimal management remain controversial., Case Summary: In this report, we describe a case of peri-Watchman device leak treated successfully with percutaneous device closure using an Amplatzer Vascular Plug II device., Discussion: The clinical implications of peri-device leaks remain controversial with general consensus to continue anticoagulation along with serial imaging for larger leaks (>5 mm). As an alternative strategy, percutaneous closure of these leaks has been attempted in hope of avoiding anticoagulation and minimizing the risk of stroke and should be studied further., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)