COVID-19 and haematological malignancy: navigating a narrow strait

Patients with haematological malignancies face unique infectious risks. Not only do their cancers typically directly affect the immune system, but therapies can cause severe myelosuppression and lymphodepletion, especially in curative settings. Vigilance to avoid life-threatening infection is a part of life for these patients and is crucial in medical decision making. With this context, the COVID-19 pandemic has understandably shaken this community, and more data to guide management are needed

HOPS 361-C's Jet Decelerating and Precessing Through NGC 2071 IR

We present a two-epoch Hubble Space Telescope (HST) near-infrared (NIR) study of NGC 2071 IR highlighting HOPS 361-C, a protostar producing an arced 0.2 parsec-scale jet. Proper motions for the brightest knots decrease from 350 to 100 km/s with increasing distance from the source. The [Fe II] and Pa$\beta$ emission line intensity ratio gives a velocity jump through each knot of 40-50 km/s. We show a new [O I] 63 $\rm \mu$m spectrum taken with the German REciever for Astronomy at Terahertz frequencies (GREAT) instrument aboard Stratospheric Observatory for Infrared Astronomy (SOFIA), which give a low jet inclination. Proper motions and jump velocities then estimate total flow speed throughout the jet. We model knot positions and speeds with a precessing jet that decelerates within the host molecular cloud. The measurements are matched with a precession period of a few thousand years and half opening angle of 15$\rm\deg$. The [Fe II] 1.26 $\rm \mu$m to 1.64 $\rm \mu$m line intensity ratio gives the extinction to each knot ranging from 5-30 mag. Relative to $\sim$14 mag of extinction through the cloud from C$^{18}$O emission maps, the jet is well embedded at a fractional depth from 1/5 to 4/5, and can interact with the cloud. Our model suggests the jet is locally dissipated over 0.2 pc. This may be because knots sweep through a wide angle, giving the cloud time to fill in cavities opened by the jet. This contrasts with nearly unidirectional protostellar jets that puncture host clouds and can propagate significantly further than a quarter pc.Comment: 24 pages, 9 figures, submitted to Ap

Metabolomic signatures of carfilzomib‐related cardiotoxicity in patients with multiple myeloma

As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib-CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post-baseline plasma samples of 60 MM patients treated with carfilzomib-based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post-baseline/baseline metabolite ratios that differ between the CVAE and no-CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T-UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21-0.94, p = 0.044) compared with the no-CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver-operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31-0.87, p = 0.023) was significantly lower in post-baseline/baseline ratios of CVAE patients compared with no-CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib-CVAE and potential cardioprotective strategies

Giving is a question of time: Response times and contributions to a real world public good

Recent experimental research has examined whether contributions to public goods can be traced back to intuitive or deliberative decision-making, using response times in public good games in order to identify the specific decision process at work. In light of conflicting results, this paper reports on an analysis of response time data from an online experiment in which over 3400 subjects from the general population decided whether to contribute to a real world public good. The between-subjects evidence confirms a strong positive link between contributing and deliberation and between free-riding and intuition. The average response time of contributors is 40 percent higher than that of free-riders. A within-subject analysis reveals that for a given individual, contributing significantly increases and free-riding significantly decreases the amount of deliberation required

JWST/MIRI detection of suprathermal OH rotational emissions: probing the dissociation of the water by Lyman alpha photons near the protostar HOPS 370

Using the MIRI/MRS spectrometer on JWST, we have detected pure rotational, suprathermal OH emissions from the vicinity of the intermediate-mass protostar HOPS 370 (OMC2/FIR3). These emissions are observed from shocked knots in a jet/outflow, and originate in states of rotational quantum number as high as 46 that possess excitation energies as large as $E_U/k = 4.65 \times 10^4$ K. The relative strengths of the observed OH lines provide a powerful diagnostic of the ultraviolet radiation field in a heavily-extinguished region ($A_V \sim 10 - 20$) where direct UV observations are impossible. To high precision, the OH line strengths are consistent with a picture in which the suprathermal OH states are populated following the photodissociation of water in its $\tilde B - X$ band by ultraviolet radiation produced by fast ($\sim 80\,\rm km\,s^{-1}$) shocks along the jet. The observed dominance of emission from symmetric ($A^\prime$) OH states over that from antisymmetric ($A^{\prime\prime}$) states provides a distinctive signature of this particular population mechanism. Moreover, the variation of intensity with rotational quantum number suggests specifically that Ly$\alpha$ radiation is responsible for the photodissociation of water, an alternative model with photodissociation by a 10$^4$ K blackbody being disfavored at a high level of significance. Using measurements of the Br$\alpha$ flux to estimate the Ly$\alpha$ production rate, we find that $\sim 4\%$ of the Ly$\alpha$ photons are absorbed by water. Combined with direct measurements of water emissions in the $\nu_2 = 1 -0$ band, the OH observations promise to provide key constraints on future models for the diffusion of Ly$\alpha$ photons in the vicinity of a shock front.Comment: 30 pages, 7 figures. Accepted for publication in ApJ Letter

Investigating Protostellar Accretion-Driven Outflows Across the Mass Spectrum: JWST NIRSpec IFU 3-5~μ\mum Spectral Mapping of Five Young Protostars

Investigating Protostellar Accretion (IPA) is a Cycle 1 JWST program using the NIRSpec+MIRI IFUs to obtain 2.9--28 $\mu$m spectral cubes of five young protostars with luminosities of 0.2 to 10,000 L$_{\odot}$ in their primary accretion phase. This paper introduces the NIRSpec 2.9--5.3 $\mu$m data of the inner 840-9000 au with spatial resolutions from 28-300 au. The spectra show rising continuum emission, deep ice absorption, emission from H$_{2}$, H~I, and [Fe~II], and the CO fundamental series in emission and absorption. Maps of the continuum emission show scattered light cavities for all five protostars. In the cavities, collimated jets are detected in [Fe~II] for the four $< 320$~L$_{\odot}$ protostars, two of which are additionally traced in Br-$\alpha$. Knots of [Fe~II] emission are detected toward the most luminous protostar, and knots of [FeII] emission with dynamical times of $< 30$~yrs are found in the jets of the others. While only one jet is traced in H$_2$, knots of H$_2$ and CO are detected in the jets of four protostars. H$_2$ is seen extending through the cavities showing they are filled by warm molecular gas. Bright H$_2$ emission is seen along the walls of a single cavity, while in three cavities, narrow shells of H$_2$ emission are found, one of which has an [Fe~II] knot at its apex. These data show cavities containing collimated jets traced in atomic/ionic gas surrounded by warm molecular gas in a wide-angle wind and/or gas accelerated by bow shocks in the jets.Comment: 30 pages, 11 figure

Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma

BackgroundProteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.MethodsExome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis.ResultsThe most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A (TMSB10/TRABD2A) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9—22.3, p = 5.42*10−7]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10. The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE (p = 1.06*10−6).ConclusionsWe identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations