Regional hydrothermal alteration and 18O-depletion of the ca. 620 Ma Huntington Mountain pluton and related rocks, Cape Breton Island, Canada

The ca. 620 Ma Huntington Mountain pluton and East Bay Hills Group, which comprise part of the Avalonian Mira terrane, Cape Breton Island, Nova Scotia, Canada, are characterized by pervasive propylitic alteration (chlorite, epidote, sericite, and Fe-Ti oxides) and low δ18O values (–3.8 to +6.2‰). This alteration is a product of interaction with hydrothermal fluids of meteoric and/or meteoric-seawater mixed origin at ~300 °C over a range of water/rock (w/r) ratios. Locally, the propylitic alteration was further overprinted by quartz-calcite-sericite alteration. Such samples have generally higher δ18OWR values (up to +9.5‰), reflecting interaction with evolved meteoric water at lower temperatures (~200 °C) and very low w/r ratios. The hydrothermal fluids responsible for widespread propylitic alteration of the Huntington Mountain-East Bay Hills complex (and regions beyond) likely entered the crust during initial rifting of the Mira terrane from Gondwana at ca. 575–550 Ma.RÉSUMÉLe pluton du mont Huntington, apparu il y a quelque 620 Ma et la succession volcanique des collines East Bay, qui font partie du terrane Mira d’Avalon, sur l’île du Cap-Breton, en Nouvelle-Écosse, au Canada, se caractérisent par une altération propylitique envahissante (chlorite, épidote, séricite, et oxydes de fer et de titane), et des teneurs faibles en δ18O (−3,8 à +6,2‰). Cette altération est le résultat de l’interaction de fluides hydrothermaux d’origine mixte météorique ou météorique et d’eau de mer, ou des deux, à une température d’environ 300 °C, selon divers rapports eau/roche. Au plan local, une altération de quartz-calcite-séricite s’est superposée à l’altération propylitique. Ces échantillons ont en règle générale des valeurs de δ18OWR supérieures (qui peuvent atteindre +9,5‰), ce qui rend compte de l’interaction de l’eau météorique évoluée à de basses températures (environ 200 °C) et de rapports eau/roche très faibles. Les fluides hydrothermaux à l’origine de l’altération propylitique très étendue du complexe du mont Huntington et des collines East Bay (et des régions au-delà) ont probablement pénétré la croûte terrestre au cours du soulèvement initial du terrane Mira, à l’époque du continent de Gondwana, il y a de cela entre 575 et 550 Ma.[Traduit par la redaction

Cross-Monitoring and Corporate Governance

We take the view that corporate governance must involve more than corporate law. Despite corporate scholars\u27 nearly exclusive focus on corporate law mechanisms for controlling managerial agency costs, shareholders are not the only constituency concerned with such costs. Given the thick web of firms\u27 contractual commitments, it should not be a surprise that other financial claimants may also attempt to control agency costs in their contracts with the firm. We hypothesize that this cross-monitoring by other claimants has value for shareholders. We examine bank loans for empirical evidence of the value of cross-monitoring. Our approach builds on prior empirical work on the value of good corporate governance, to which we add data on the presence of bank loans and their interactions with free cash flow, governance indices, and individual corporate governance provisions. To our knowledge, ours is the first study to measure the performance effects of bank debt as a device for reducing managerial agency costs, and the first study on the interaction of ongoing bank monitoring with corporate governance arrangements. We find strong evidence that bank monitoring adds value. In effect, bank monitoring can counteract somewhat the value-decreasing effects of managerial entrenchment. Bank monitoring may substitute for good corporate governance

A Spitzer c2d Legacy Survey to Identify and Characterize Disks with Inner Dust Holes

Understanding how disks dissipate is essential to studies of planet formation. However, identifying exactly how dust and gas dissipates is complicated due to difficulty in finding objects clearly in the transition of losing their surrounding material. We use Spitzer IRS spectra to examine 35 photometrically-selected candidate cold disks (disks with large inner dust holes). The infrared spectra are supplemented with optical spectra to determine stellar and accretion properties and 1.3mm photometry to measure disk masses. Based on detailed SED modeling, we identify 15 new cold disks. The remaining 20 objects have IRS spectra that are consistent with disks without holes, disks that are observed close to edge-on, or stars with background emission. Based on these results, we determine reliable criteria for identifying disks with inner holes from Spitzer photometry and examine criteria already in the literature. Applying these criteria to the c2d surveyed star-forming regions gives a frequency of such objects of at least 4% and most likely of order 12% of the YSO population identified by Spitzer. We also examine the properties of these new cold disks in combination with cold disks from the literature. Hole sizes in this sample are generally smaller than for previously discovered disks and reflect a distribution in better agreement with exoplanet orbit radii. We find correlations between hole size and both disk and stellar masses. Silicate features, including crystalline features, are present in the overwhelming majority of the sample although 10 micron feature strength above the continuum declines for holes with radii larger than ~7 AU. In contrast, PAHs are only detected in 2 out of 15 sources. Only a quarter of the cold disk sample shows no signs of accretion, making it unlikely that photoevaporation is the dominant hole forming process in most cases.Comment: 24 pages, 18 figures and 8 tables. Fixed a typo in Table

The Prevalence of Cognitive Impairment Among Adults With Incident Heart Failure: The “Reasons for Geographic and Racial Differences in Stroke” (REGARDS) Study

Background Cognitive impairment (CI) is estimated to be present in 25%–80% of heart failure (HF) patients, but its prevalence at diagnosis is unclear. To improve our understanding of cognition in HF, we determined the prevalence of CI among adults with incident HF in the REGARDS study. Methods and Results REGARDS is a longitudinal cohort study of adults ≥45 years of age recruited in the years 2003–2007. Incident HF was expert adjudicated. Cognitive function was assessed with the Six-Item Screener. The prevalence of CI among those with incident HF was compared with the prevalence of CI among an age-, sex-, and race-matched cohort without HF. The 436 participants with incident HF had a mean age of 70.3 years (SD 8.9), 47% were female, and 39% were black. Old age, black race, female sex, less education, and anticoagulation use were associated with CI. The prevalence of CI among participants with incident HF (14.9% [95% CI 11.7%–18.6%]) was similar to the non-HF matched cohort (13.4% [11.6%–15.4%]; P < .43). Conclusions A total of 14.9% of the adults with incident HF had CI, suggesting that the majority of cognitive decline occurs after HF diagnosis. Increased awareness of CI among newly diagnosed patients and ways to mitigate it in the context of HF management are warranted

The Far-Ultraviolet "Continuum" in Protoplanetary Disk Systems II: CO Fourth Positive Emission and Absorption

We exploit the high sensitivity and moderate spectral resolution of the $HST$-Cosmic Origins Spectrograph to detect far-ultraviolet spectral features of carbon monoxide (CO) present in the inner regions of protoplanetary disks for the first time. We present spectra of the classical T Tauri stars HN Tau, RECX-11, and V4046 Sgr, representative of a range of CO radiative processes. HN Tau shows CO bands in absorption against the accretion continuum. We measure a CO column density and rotational excitation temperature of N(CO) = 2 +/- 1 $\times$ 10$^{17}$ cm$^{-2}$ and T_rot(CO) 500 +/- 200 K for the absorbing gas. We also detect CO A-X band emission in RECX-11 and V4046 Sgr, excited by ultraviolet line photons, predominantly HI LyA. All three objects show emission from CO bands at $\lambda$ $>$ 1560 \AA, which may be excited by a combination of UV photons and collisions with non-thermal electrons. In previous observations these emission processes were not accounted for due to blending with emission from the accretion shock, collisionally excited H$_{2}$, and photo-excited H2; all of which appeared as a "continuum" whose components could not be separated. The CO emission spectrum is strongly dependent upon the shape of the incident stellar LyA emission profile. We find CO parameters in the range: N(CO) 10$^{18-19}$ cm$^{-2}$, T_{rot}(CO) > 300 K for the LyA-pumped emission. We combine these results with recent work on photo- and collisionally-excited H$_{2}$ emission, concluding that the observations of ultraviolet-emitting CO and H2 are consistent with a common spatial origin. We suggest that the CO/H2 ratio in the inner disk is ~1, a transition between the much lower interstellar value and the higher value observed in solar system comets today, a result that will require future observational and theoretical study to confirm.Comment: 12 pages, 7 figures, 3 tables. ApJ - accepte

A Unique Population of Ventral Tegmental Area Neurons Inhibits the Lateral Habenula to Promote Reward

Lateral habenula (LHb) neurons convey aversive and negative reward conditions through potent indirect inhibition of ventral tegmental area (VTA) dopaminergic neurons. While VTA dopaminergic neurons reciprocally project to the LHb, the electrophysiological properties and the behavioral consequences associated with selective manipulations of this circuit are unknown. Here, we identify a novel inhibitory input to the LHb arising from a unique population of VTA neurons expressing dopaminergic markers. Optogenetic activation of this circuit resulted in no detectable dopamine release in LHb brain slices. Instead, stimulation produced GABA-mediated inhibitory synaptic transmission, which suppressed the firing of postsynaptic LHb neurons in brain slices and increased the spontaneous firing rate of VTA dopaminergic neurons in vivo. Furthermore, in vivo activation of this pathway produced reward-related phenotypes that were dependent on intra-LHb GABAA receptor signaling. These results suggest that non-canonical inhibitory signaling by these hybrid dopaminergic-GABAergic neurons act to suppress LHb output under rewarding conditions

A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor

© 2020 The Author(s). Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and a significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, in participants with IPF. Methods: This was a phase 1b, randomised, double-blind (sponsor unblind) study, conducted in the UK (two clinical sites, one imaging unit) between June 2017 and July 2018 (NCT03069989). Participants with a definite or probable diagnosis of IPF received a single nebulised dose of 1000 mcg GSK3008348 or placebo (ratio 5:2) in two dosing periods. In period 1, safety and PK assessments were performed up to 24 h post-dose; in period 2, after a 7-day to 28-day washout, participants underwent a total of three positron emission tomography (PET) scans: Baseline, Day 1 (~ 30 min post-dosing) and Day 2 (~ 24 h post-dosing), using a radiolabelled αvβ6-specific ligand, [18F]FB-A20FMDV2. The primary endpoint was whole lung volume of distribution (VT), not corrected for air volume, at ~ 30 min post-dose compared with pre-dose. The study success criterion, determined using Bayesian analysis, was a posterior probability (true % reduction in VT > 0%) of ≥80%. Results: Eight participants with IPF were enrolled and seven completed the study. Adjusted posterior median reduction in uncorrected VT at ~ 30 min after GSK3008348 inhalation was 20% (95% CrI:-9 to 42%). The posterior probability that the true % reduction in VT > 0% was 93%. GSK3008348 was well tolerated with no reports of serious adverse events or clinically significant abnormalities that were attributable to study treatment. PK was successfully characterised showing rapid absorption followed by a multiphasic elimination. Conclusions: This study demonstrated engagement of the αvβ6 integrin target in the lung following nebulised dosing with GSK3008348 to participants with IPF. To the best of our knowledge this is the first time a target-specific PET radioligand has been used to assess target engagement in the lung, not least for an inhaled drug. Trial registration: Clinicaltrials.gov: NCT03069989; date of registration: 3 March 2017