Comparative outcomes between COVID-19 and influenza patients placed on veno-venous extracorporeal membrane oxygenation for severe ARDS

Background ECMO is an established supportive adjunct for patients with severe, refractory ARDS from viral pneumonia. However, the exact role and timing of ECMO for COVID-19 patients remains unclear. Methods We conducted a retrospective comparison of the first 32 patients with COVID-19-associated ARDS to the last 28 patients with influenza-associated ARDS placed on V-V ECMO. We compared patient factors between the two cohorts and used survival analysis to compare the hazard of mortality over sixty days post-cannulation.Results COVID-19 patients were older (mean 47.8 vs. 41.2 years, p = 0.033), had more ventilator days before cannulation (mean 4.5 vs. 1.5 days, p < 0.001). Crude in-hospital mortality was significantly higher in the COVID-19 cohort at 65.6% (n = 21/32) versus 36.3% (n = 11/28, p = 0.041). The adjusted hazard ratio over sixty days for COVID-19 patients was 2.81 (95% CI 1.07, 7.35) after adjusting for age, race, ECMO-associated organ failure, and Charlson Comorbidity Index. Conclusion ECMO has a role in severe ARDS associated with COVID-19 but providers should carefully weigh patient factors when utilizing this scarce resource in favor of influenza pneumonia

Dgp71WD is required for the assembly of the acentrosomal meiosis I spindle, and is not a general targeting factor for the γ-TuRC

Dgp71WD/Nedd1 proteins are essential for mitotic spindle formation. In human cells, Nedd1 targets γ-tubulin to both centrosomes and spindles, but in other organisms the function of Dgp71WD/Nedd1 is less clear. In Drosophila cells, Dgp71WD plays a major part in targeting γ-tubulin to spindles, but not centrosomes, while in Xenopus egg extracts, Nedd1 acts as a more general microtubule (MT) organiser that can function independently of γ-tubulin. The interpretation of these studies, however, is complicated by the fact that some residual Dgp71WD/Nedd1 is likely present in the cells/extracts analysed. Here we generate a Dgp71WD null mutant lacking all but the last 12 nucleotides of coding sequence. The complete loss of Dgp71WD has no quantifiable effect on γ-tubulin or Centrosomin recruitment to the centrosome in larval brain cells. The recruitment of γ-tubulin to spindle MTs, however, is severely impaired, and spindle MT density is reduced in a manner that is indistinguishable from cells lacking Augmin or γ-TuRC function. In contrast, the absence of Dgp71WD leads to defects in the assembly of the acentrosomal female Meiosis I spindle that are more severe than those seen in Augmin or γ-TuRC mutants, indicating that Dgp71WD has additional functions that are independent of these complexes in oocytes. Moreover, the localisation of bicoid RNA during oogenesis, which requires γ-TuRC function, is unperturbed in Dgp71WD(120) mutants. Thus, Dgp71WD is not simply a general cofactor required for γ-TuRC and/or Augmin targeting, and it appears to have a crucial role independent of these complexes in the acentrosomal Meiosis I spindle

Gaseous Electronics

Contains reports on two research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E

A quasi classical approach to electron impact ionization

A quasi classical approximation to quantum mechanical scattering in the Moeller formalism is developed. While keeping the numerical advantage of a standard Classical--Trajectory--Monte--Carlo calculation, our approach is no longer restricted to use stationary initial distributions. This allows one to improve the results by using better suited initial phase space distributions than the microcanonical one and to gain insight into the collision mechanism by studying the influence of different initial distributions on the cross section. A comprehensive account of results for single, double and triple differential cross sections for atomic hydrogen will be given, in comparison with experiment and other theories.Comment: 21 pages, 10 figures, submitted to J Phys

Organization of Multinational Activities and Ownership Structure

We develop a model in which multinational investors decide about the modes of organization, the locations of production, and the markets to be served. Foreign investments are driven by market-seeking and cost-reducing motives. We further assume that investors face costs of control that vary among sectors and increase in distance. The results show that (i) production intensive sectors are more likely to operate a foreign business independent of the investment motive, (ii) that distance may have a non-monotonous effect on the likelihood of horizontal investments, and (iii) that globalization, if understood as reducing distance, leads to more integration

Vertical Distribution, Parallel Trade, and Price Divergence in Integrated Markets

We develop a model of vertical pricing in which an original manufacturer sets wholesale prices in two markets that are integrated at the distributor level by parallel imports (PI). The manufacturing firm needs to set these two prices to balance three competing interests: restricting competition in the PI-recipient market, avoiding resource wastes due to actual trade, and reducing the double-markup problem in the PI-source nation. These trade-offs imply the counterintuitive result that both wholesale and retail prices could diverge as a result of declining trading costs, even as the volume of PI increases. Thus, in some circumstances it may be misleading to think of PI as an unambiguous force for price integration

HOx and NOx production in oxidation flow reactors via photolysis of isopropyl nitrite, isopropyl nitrite-d(7), and 1,3-propyl dinitrite at lambda=254, 350, and 369 nm

Oxidation flow reactors (OFRs) are an emerging technique for studying the formation and oxidative aging of organic aerosols and other applications. In these flow reactors, hydroxyl radicals (OH), hydroperoxyl radicals (HO2), and nitric oxide (NO) are typically produced in the following ways: photolysis of ozone (O-3) at), = 254 nm, photolysis of H2O at), = 185 nm, and via reactions of O(D-1) with H2O and nitrous oxide (N2O); O(D-1) is formed via photolysis of O-3 at = 254 nm and/or N2O at = 185 nm. Here, we adapt a complementary method that uses alkyl nitrite photolysis as a source of OH via its production of HO2 and NO followed by the reaction NO + HO2 -> NO2 + OH. We present experimental and model characterization of the OH exposure and NO, levels generated via photolysis of C3 alkyl nitrites (isopropyl nitrite, perdeuterated isopropyl nitrite, 1,3-propyl dinitrite) in the Potential Aerosol Mass (PAM) OFR as a function of photolysis wavelength (7, = 254 to 369 nm) and organic nitrite concentration (0.5 to 20 ppm). We also apply this technique in conjunction with chemical ionization mass spectrometer measurements of multifunctional oxidation products generated following the exposure of a-Pinene to HO, and NO, obtained using both isopropyl nitrite and O-3 + H2O + N2O as the radical precursors.Peer reviewe

Pulsed Feedback Defers Cellular Differentiation

Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable “polyphasic” positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a “timer” that operates over timescales much longer than a cell cycle