The productivity advantages of large cities: Distinguishing agglomeration from firm selection

Firms are more productive on average in larger cities. Two explanations have been offered: agglomeration economies (larger cities promote interactions that increase productivity) and firm selection (larger cities toughen competition allowing only the most productive to survive). To distinguish between them, we nest a generalised version of a seminal firm selection model and a standard model of agglomeration. Stronger selection in larger cities left truncates the productivity distribution whereas stronger agglomeration right shifts and dilates the distribution. We assess the relative importance of agglomeration and firm selection using French establishment level data and a new quantile approach. Spatial productivity differences in France are mostly explained by agglomeration.agglomeration; firm selection; productivity; cities

ALMA captures feeding and feedback from the active galactic nucleus in NGC 613

We report ALMA observations of CO(3-2) emission in the Seyfert/nuclear starburst galaxy NGC 613, at a spatial resolution of 17 pc, as part of our NUclei of GAlaxies (NUGA) sample. Our aim is to investigate the morphology and dynamics of the gas inside the central kiloparsec, and to probe nuclear fueling and feedback phenomena. The morphology of CO(3-2) line emission reveals a two-arm trailing nuclear spiral at r≤ 100 pc and a circumnuclear ring at a radius of ∼350 pc that is coincident with the star-forming ring seen in the optical images. Also, we find evidence for a filamentary structure connecting the ring and the nuclear spiral. The ring reveals two breaks into two winding spiral arms corresponding to the dust lanes in the optical images. The molecular gas in the galaxy disk is in a remarkably regular rotation, however the kinematics in the nuclear region are very skewed. The nuclear spectrum of CO and dense gas tracers HCN(4-3), HCO+(4-3), and CS(7-6) show broad wings up to \ub1300 km s-1, associated with a molecular outflow emanating from the nucleus (r ∼ 25 pc). We derive a molecular outflow mass Mout=2 7 106 M⊙ and a mass outflow rate of M out = 27 M⊙ yr-1. The molecular outflow energetics exceed the values predicted by AGN feedback models: the kinetic power of the outflow corresponds to PK, out=20%LAGN and the momentum rate is M outv ∼400LAGN/c. The outflow is mainly boosted by the AGN through entrainment by the radio jet, but given the weak nuclear activity of NGC 613, we might be witnessing a fossil outflow resulting from a previously strong AGN that has now faded. Furthermore, the nuclear trailing spiral observed in CO emission is inside the inner Lindblad resonance ring of the bar. We compute the gravitational torques exerted in the gas to estimate the efficiency of the angular momentum exchange. The gravity torques are negative from 25 to 100 pc and the gas loses its angular momentum in a rotation period, providing evidence for a highly efficient inflow towards the center. This phenomenon shows that the massive central black hole has significant dynamical influence on the gas, triggering the inflowing of molecular gas to feed the black hole

PKS 1413+135: OH and H i at z = 0.247 with MeerKAT

The BL Lac object PKS 1413+135 was observed by the Large Survey Project MeerKAT Absorption Line Survey (MALS) in the L-band, at 1139 MHz and 12931379 MHz, targeting the HI and OH lines in absorption at z=0.24671. The radio continuum might come from the nucleus of the absorbing galaxy or from a background object at redshift lower than 0.5, as suggested by the absence of gravitational images. The HI absorption line is detected at a high signal-To-noise ratio, with a narrow central component, and with a red wing, confirming previous results. The OH 1720 MHz line is clearly detected in (maser) emission, peaking at a velocity shifted by-10 to-15 km s-1 with respect to the HI peak. The 1612 MHz line is lost due to radio frequency interference. The OH 1667 MHz main line is tentatively detected in absorption, but not the 1665 MHz line. Over 30 years a high variability is observed in optical depths, due to the rapid changes of the line of sight caused by the superluminal motions of the radio knots. The HI line has varied by 20% in depth, while the OH-1720 MHz depth has varied by a factor of ∼3. The position of the central velocity and the widths also varied. The absorbing galaxy is an early-Type spiral (maybe S0) seen edge-on, with a prominent dust lane, covering the whole disk. Given the measured mass concentration and the radio continuum size at centimeter wavelengths (100 mas corresponding to 400 pc at z=0.25), the width of the absorption lines from the nuclear regions are expected up to 250 km s-1. The narrowness of the observed lines (< 15 km s-1) suggests that the absorption comes from an outer gas ring, as frequently observed in S0 galaxies. The millimetric lines are even narrower (< 1 km s-1), which corresponds to the continuum size restricted to the core. The radio core is covered by individual 1 pc molecular clouds, whose column density is a few 1022 cm-2, which is compatible with the gas screen detected in X-rays

Discovery of Hydrogen Radio Recombination Lines at z = 0.89 toward PKS 1830-211

We report the detection of stimulated hydrogen radio recombination line (RRL) emission from ionized gas in a z = 0.89 galaxy using 580-1670 MHz observations from the MeerKAT Absorption Line Survey. The RRL emission originates in a galaxy that intercepts and strongly lenses the radio blazar PKS 1830−211 (z = 2.5). This is the second detection of RRLs outside of the local Universe and the first clearly associated with hydrogen. We detect effective H144α (and H163α) transitions at observed frequencies of 1156 (798) MHz by stacking 17 (27) RRLs with 21σ (14σ) significance. The RRL emission contains two main velocity components and is coincident in velocity with H i 21 cm and OH 18 cm absorption. We use the RRL spectral line energy distribution and a Bayesian analysis to constrain the density (n e ) and the volume-averaged path length (ℓ) of the ionized gas. We determine log ( n e ) = 2.0 − 0.7 + 1.0 cm−3 and log ( ℓ ) = − 0.7 − 1.1 + 1.1 pc toward the northeast (NE) lensed image, likely tracing the diffuse thermal phase of the ionized ISM in a thin disk. Toward the southwest (SW) lensed image, we determine log ( n e ) = 3.2 − 1.0 + 0.4 cm−3 and log ( ℓ ) = − 2.7 − 0.2 + 1.8 pc, tracing gas that is more reminiscent of H scii regions. We estimate a star formation (surface density) rate of ΣSFR ∼ 0.6 M ⊙ yr−1 kpc−2 or SFR ∼ 50 M ⊙ yr−1, consistent with a star-forming main-sequence galaxy of M ⋆ ∼ 1011 M ⊙. The discovery presented here opens up the possibility of studying ionized gas at high redshifts using RRL observations from current and future (e.g., SKA and ngVLA) radio facilities

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Population pharmacokinetics of asciminib in tyrosine kinase inhibitor-treated patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic and acute phases

Background: Asciminib, a first-in-class highly potent BCR-ABL1 inhibitor has shown superior efficacy compared to the existing tyrosine kinase inhibitor TKI in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, treated with ≥2 TKIs. This study aimed to describe pharmacokinetic properties of asciminib and to identify clinically relevant covariates impacting its exposure. Methods: A population pharmacokinetics (PopPK) model was developed using a two-compartment model with delayed first-order absorption and elimination. The analysis included pharmacokinetics data from two clinical studies (Phases 1 and 3) involving 353 patients, with total daily asciminib doses range of 20-400 mg. Results: The nominal total daily dose was incorporated as a structural covariate on clearance (CL), and body weight (BW) was included as a structural covariate via allometric scaling on CL and central volume. Renal function and formulation were included as statistically significant covariates on CL and absorption (ka), respectively. The simulation results revealed a modest but clinically non-significant effect of baseline BW and renal function on ka. Covariates such as baseline demographic and disease characteristics, hepatic function, and T315I mutation were not statistically significant and were not incorporated in the final model. Additionally, the final model-based simulations demonstrated comparable exposure and CL for asciminib 40 mg bid and 80 mg qd (an alternative regimen not studied in the Phase 3 trial), as well as similar PK properties in patients with and without T315I mutation. Conclusions: The final PopPK model adequately characterized the pharmacokinetics properties of asciminib and assessed the impact of key covariates on its exposure. The model not only corroborates the use of the recommended asciminib dose of 40 mg bid, but also substantiates the use of 80 mg qd to facilitate patient’s compliance