Turbulent Mixing in the Outer Solar Nebula

The effects of turbulence on the mixing of gases and dust in the outer Solar nebula are examined using 3-D MHD calculations in the shearing-box approximation with vertical stratification. The turbulence is driven by the magneto-rotational instability. The magnetic and hydrodynamic stresses in the turbulence correspond to an accretion time at the midplane about equal to the lifetimes of T Tauri disks, while accretion in the surface layers is thirty times faster. The mixing resulting from the turbulence is also fastest in the surface layers. The mixing rate is similar to the rate of radial exchange of orbital angular momentum, so that the Schmidt number is near unity. The vertical spreading of a trace species is well-matched by solutions of a damped wave equation when the flow is horizontally-averaged. The damped wave description can be used to inexpensively treat mixing in 1-D chemical models. However, even in calculations reaching a statistical steady state, the concentration at any given time varies substantially over horizontal planes, due to fluctuations in the rate and direction of the transport. In addition to mixing species that are formed under widely varying conditions, the turbulence intermittently forces the nebula away from local chemical equilibrium. The different transport rates in the surface layers and interior may affect estimates of the grain evolution and molecular abundances during the formation of the Solar system.Comment: To appear in the Astrophysical Journal; 20 pages, 9 figure

Closed-form expressions for particle relative velocities induced by turbulence

In this note we present complete, closed-form expressions for random relative velocities between colliding particles of arbitrary size in nebula turbulence. These results are exact for very small particles (those with stopping times much shorter than the large eddy overturn time) and are also surprisingly accurate in complete generality (that is, also apply for particles with stopping times comparable to, or much longer than, the large eddy overturn time). We note that some previous studies may have adopted previous simple expressions, which we find to be in error regarding the size dependence in the large particle regime.Comment: 8 pages, accepted as Research Note by A&

Dust Size Growth and Settling in a Protoplanetary Disk

We have studied dust evolution in a quiescent or turbulent protoplanetary disk by numerically solving coagulation equation for settling dust particles, using the minimum mass solar nebular model. As a result, if we assume an ideally quiescent disk, the dust particles settle toward the disk midplane to form a gravitationally unstable layer within 2x10^3 - 4x10^4 yr at 1 - 30 AU, which is in good agreement with an analytic calculation by Nakagawa, Sekiya, & Hayashi (1986) although they did not take into account the particle size distribution explicitly. In an opposite extreme case of a globally turbulent disk, on the other hand, the dust particles fluctuate owing to turbulent motion of the gas and most particles become large enough to move inward very rapidly within 70 - 3x10^4 yr at 1 - 30 AU, depending on the strength of turbulence. Our result suggests that global turbulent motion should cease for the planetesimal formation in protoplanetary disks.Comment: 27 pages, 8 figures, accepted for publication in the Ap

Reducing the risk of iatrogenic Creutzfeldt–Jakob disease by improving the cleaning of neurosurgical instruments

Background: In all, there have been 178 variant Creutzfeldt–Jakob disease (vCJD) patients diagnosed in the UK, with an estimated maximum 1:2000 carriage rate based on archived appendix and tonsil tissue, implying that infection may be rare but carriage relatively frequent. Previous workers have identified that maintenance of surgical instruments in a humid atmosphere after use and prior to cleaning assists cleaning efficacy. Recently the Department of Health/Advisory Committee on Dangerous Pathogens UK have recommended a surgical instrument cleanliness threshold post cleaning of <5 μg protein per instrument side. Aim: To quantify cleanliness of neurosurgical instruments and to investigate cost-effective measures for improved cleaning. Methods: Two instrument protein quantification methods were used: one based on the International Standard (15883 series) using sodium dodecyl sulphate elution and ortho-phthalaldehyde reaction, and a second in-situ protein fluorescence detection system (ProReveal) providing results per instrument side. In-vitro investigation of the efficacy of some commercial and in-house pre-clean wetting agents was undertaken using artificial test soil and stainless steel discs under standard conditions. In-vivo evaluation of best-performing in-vitro agents was undertaken on craniotomy sets. Findings: ProReveal technology demonstrated that 163 out of 187 (87%) neurosurgical instruments had <5 μg residual protein per instrument side. The use of proprietary National Health Service plastic bags and sterile water-soaked wound pads were equivalent in efficacy to commercial pre-cleaning wetting products and significantly less expensive. Conclusion: Although we demonstrate low in-situ protein levels on neurosurgical instruments and the beneficial effects of keeping instruments moist, other cleaning critical-control points such as instrument loading patterns should also be monitored

Evolution of Young Brown Dwarf Disks in the Mid-Infrared

We have imaged two bona-fide brown dwarfs with TReCS/GEMINI-S and find mid-infrared excess emission that can be explained by optically thick dust disk models. In the case of the young ($\approx$2Myr) Cha H$\alpha$1 we measure fluxes at 10.4$\mu$m and 12.3$\mu$m that are fully consistent with a standard flared disk model and prominent silicate emission. For the $\approx$ 10Myr old brown dwarf 2MASS1207-3932 located in the TW Hydrae association we find excess emission at 8.7$\mu$m and 10.4$\mu$m with respect to its photosphere, and confirm disk accretion as likely cause of its strong activity. Disks around brown dwarfs likely last at least as long as their low-mass stellar counterparts in the T-Tauri phase. Grain growth, dust settling, and evolution of the geometry of brown dwarfs disks may appear on a timescale of 10Myr and can be witnessed by observations in the mid-infrared.Comment: 6 pages, 4 figure

3D Simulations of Betelgeuse's Bow Shock

Betelgeuse, the bright, cool red supergiant in Orion, is moving supersonically relative to the local interstellar medium. The star emits a powerful stellar wind which collides with this medium, forming a cometary structure, a bow shock, pointing in the direction of motion. We present the first 3D hydrodynamic simulations of the formation and evolution of Betelgeuse's bow shock. The models include realistic low temperature cooling and cover a range of plausible interstellar medium densities and stellar velocities between 0.3 - 1.9 cm-3 and 28 - 73 km/s. We show that the flow dynamics and morphology of the bow shock differ substantially due to the preferential growth of Rayleigh-Taylor or Kelvin-Helmholtz instabilities in the models. The former dominate the models with slow stellar velocities resulting in a clumpy bow shock sub-structure, whereas the latter produce a smoother, more layered sub-structure in the fast models. If the mass in the bow shock shell is low, as seems to be implied by the AKARI luminosities (~0.003 Msun), then Betelgeuse's bow shock is very young and is unlikely to have reached a steady state. The circular nature of the bow shock shell is consistent with this conclusion. Thus, our results suggest that Betelgeuse entered the red supergiant phase only recently.Comment: Minor revisions, replaced Fig. 1, 15, and 16, added movies. For a pdf version with higher resolution, see A&A: Forthcomin

The Spectral Energy Distribution of HH30 IRS: Constraining The Circumstellar Dust Size Distribution

We present spectral energy distribution (SED) models for the edge-on classical T Tauri star HH30 IRS that indicate dust grains have grown to larger than 50 microns within its circumstellar disk. The disk geometry and inclination are known from previous modeling of multiwavelength Hubble Space Telescope images and we use the SED to constrain the dust size distribution. Model spectra are shown for different circumstellar dust models: a standard ISM mixture and larger grain models. As compared to ISM grains, the larger dust grain models have a shallower wavelength dependent opacity. Models with the larger dust grains provide a good match to the currently available data, but mid and far-IR observations are required to more tightly constrain the dust size distribution. The accretion luminosity in our models is L_acc<0.2 L_star corresponding to an accretion rate of 4E-9M_sun/yr. Dust size distributions that are simple power-law extensions (i.e., no exponential cutoff) yield acceptable fits to the optical/near-IR but too much emission at mm wavelengths and require larger disk masses. Such a simple size distribution would not be expected in an environment such as the disk of HH30 IRS, particularly over such a large range in grain sizes. However, its ability to adequately characterize the grain populations may be determined from more complete observational sampling of the SED in the mid to far-IR.Comment: ApJ Accepte

61MO Biomarker analysis of men with enzalutamide (enza)-resistant metastatic castration-resistant prostate cancer (mCRPC) treated with pembrolizumab (pembro) + enza in KEYNOTE-199

Background: In KEYNOTE-199 (NCT02787005), pembro + enza had durable antitumor activity in enza-refractory mCRPC. We evaluated the association between prespecified biomarkers and clinical outcomes. Methods: Cohorts 4 (C4; RECIST-measurable disease) and 5 (C5; nonmeasurable, bone-predominant disease) enrolled men with chemotherapy-naive mCRPC, irrespective of PD-L1 status, that progressed after initial response to enza. We evaluated TMB by whole exome sequencing (n = 64), PD-L1 combined positive score (CPS) by IHC (n = 124), and 18-gene T-cell–inflamed gene expression profile (TcellinfGEP) by NanoString (n = 51). Outcomes were DCR, PFS, PSA response, PSA progression, OS, and ORR per blinded independent review (C4 only). Significance of continuous biomarkers (CPS, TMB, GEP) was prespecified at 0.05 for 1-sided P values from logistic (ORR, DCR, PSA response) and Cox proportional hazard (PFS, OS, PSA progression) regression adjusted for ECOG PS. Results: In C4, ORR was 10% (5/48) in pts with evaluable TMB data and 12% (10/81) in pts with CPS data. In C4 and C5, 16% (10/64) and 14% (17/124) of pts with TMB and CPS data, respectively, achieved a PSA response. TMB was significantly associated with DCR (P = 0.03) and trended toward an association with PSA response (P = 0.08). TMB (AUROC [95% CI]: 0.68 [0.51-0.86]), but not CPS (0.54 [0.41-0.67]) or TcellinfGEP (0.55 [0.37-0.74]), enriched for PSA response. TMB (P = 0.04), but not CPS (P = 0.57) or TcellinfGEP (P = 0.32), was significantly associated with PSA progression. There was 1 MSI-H pt (per Promega PCR assay); this pt achieved an objective and PSA response and had PFS \u3e6 months. TMB, CPS, and TcellinfGEP were not associated with PFS or OS. There was a low prevalence of TMB ≥175 mut/exome (11%) and TcellinfGEP-high (≥−0.318; 16%). Conclusions: In this biomarker analysis of KEYNOTE-199 C4-C5, PD-L1 CPS and TcellinfGEP were not significantly associated with clinical outcome. Despite the low prevalence of TMB ≥175 mut/exome, TMB was positively associated with outcomes of pembro + enza in pts with mCRPC. The sample sizes for the exploratory analyses were small, and results should be interpreted with caution

Trial of Dexamethasone for Chronic Subdural Hematoma

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.)