On the central symmetry of the circumstellar envelope of RS Cnc

We present a phenomenological study of CO(1-0) and CO(2-1) emission from the circumstellar envelope (CSE) of the Asymptotic Giant Branch (AGB) star RS\,Cnc. It reveals departures from central symmetry that turn out to be efficient tools for the exploration of some of the CSE properties. We use a wind model including a bipolar flow with a typical wind velocity of $\sim$8 km\,s$^{-1}$ decreasing to $\sim$2 km\,s$^{-1}$ near the equator to describe Doppler velocity spectral maps obtained by merging data collected at the IRAM Plateau de Bure Interferometer and Pico Veleta single dish radio telescope. Parameters describing the wind morphology and kinematics are obtained, together with the radial dependence of the gas temperature in the domain of the circumstellar envelope probed by the CO observations. Significant north-south central asymmetries are revealed by the analysis, which we quantify using a simple phenomenological description. The origin of such asymmetries is unclear.Comment: accepted for publication in Research in Astronomy and Astrophysics (RAA

HI and CO in the circumstellar environment of the S-type star RS Cnc

This paper presents interferometric and single-dish CO observations along with HI data obtained for the oxygen-rich semi-regular variable RS Cnc, in order to probe its circumstellar environment at different scales. With the Plateau de Bure Interferometer and the IRAM 30-m telescope, we detect both the CO(1-0) and the CO(2-1) rotational lines from RS Cnc. The line profiles are composite, with two components of half-width ~2 km/s and ~8 km/s respectively. Whereas the narrow velocity component seems to originate from an equatorial disk in the central part of the CO envelope, the broad component reveals a bipolar structure, with a north-south velocity gradient. In addition, we obtain new HI data on the source and around it in a field of almost 1 square degree. The HI line is centered at v_LSR = 7 km/s in agreement with CO observations. A new reduction process reveals a complex extended structure in the northwest direction, of estimated size ~18 arcmin, with a PA (~310 degrees) opposite to the direction of the stellar proper motion (~140 degrees). We derive an HI mass of ~3 10^-2 M_sun for this structure. Based on a non-spherical simulation, we find that this structure is consistent with arising from the interaction of the star undergoing mass loss at an average rate of ~10^-7 M_sun.yr^-1 over ~2-3 10^5 years with the interstellar medium. This work illustrates the powerful complementarity of CO and HI observations with regard to a more complete description of circumstellar environments around AGB stars.Comment: accepted for publication in A&

Copious Amounts of Dust and Gas in a z=7.5 Quasar Host Galaxy

We present IRAM/NOEMA and JVLA observations of the quasar J1342+0928 at z=7.54 and report detections of copious amounts of dust and [CII] emission in the interstellar medium (ISM) of its host galaxy. At this redshift, the age of the universe is 690 Myr, about 10% younger than the redshift of the previous quasar record holder. Yet, the ISM of this new quasar host galaxy is significantly enriched by metals, as evidenced by the detection of the [CII] 158micron cooling line and the underlying far-infrared (FIR) dust continuum emission. To the first order, the FIR properties of this quasar host are similar to those found at a slightly lower redshift (z~6), making this source by far the FIR-brightest galaxy known at z>7.5. The [CII] emission is spatially unresolved, with an upper limit on the diameter of 7 kpc. Together with the measured FWHM of the [CII] line, this yields a dynamical mass of the host of <1.5x10^11 M_sun. Using standard assumptions about the dust temperature and emissivity, the NOEMA measurements give a dust mass of (0.6-4.3)x10^8 M_sun. The brightness of the [CII] luminosity, together with the high dust mass, imply active ongoing star formation in the quasar host. Using [CII]-SFR scaling relations, we derive star formation rates of 85-545 M_sun/yr in the host, consistent with the values derived from the dust continuum. Indeed, an episode of such past high star formation is needed to explain the presence of ~10^8 M_sun of dust implied by the observations.Comment: 8 pages, 4 figures. Published in ApJ Letter

First constraints of dense molecular gas at z~7.5 from the quasar P\=oniu\=a'ena

We report the detection of CO(6-5) and CO(7-6) and their underlying continua from the host galaxy of quasar J100758.264+211529.207 (P\=oniu\=a'ena) at z=7.5419, obtained with the NOrthern Extended Millimeter Array (NOEMA). P\=oniu\=a'ena belongs to the HYPerluminous quasars at the Epoch of ReionizatION (HYPERION) sample of 17 $z>6$ quasars selected to be powered by supermassive black holes (SMBH) which experienced the fastest mass growth in the first Gyr of the Universe. The one reported here is the highest-redshift measurement of the cold and dense molecular gas to date. The host galaxy is unresolved and the line luminosity implies a molecular reservoir of $\rm M(H_2)=(2.2\pm0.2)\times 10^{10}$ $\rm M_\odot$, assuming a CO spectral line energy distribution typical of high-redshift quasars and a conversion factor $\alpha=0.8$ $\rm M_{\odot} (K\,km \, s^{-1} \,pc^{2})^{-1}$. We model the cold dust spectral energy distribution (SED) to derive a dust mass of M$_{\rm dust} =(2.1\pm 0.7)\times 10^8$ $\rm M_\odot$, and thus a gas to dust ratio $\sim100$. Both the gas and dust mass are not dissimilar from the reservoir found for luminous quasars at $z\sim6$. We use the CO detection to derive an estimate of the cosmic mass density of $\rm H_2$, $\Omega_{H_2} \simeq 1.31 \times 10^{-5}$. This value is in line with the general trend suggested by literature estimates at $z < 7$ and agrees fairly well with the latest theoretical expectations of non-equilibrium molecular-chemistry cosmological simulations of cold gas at early times.Comment: Submitted to ApJ Letter

A new interdisciplinary treatment strategy versus usual medical care for the treatment of subacromial impingement syndrome: a randomized controlled trial

BACKGROUND: Subacromial impingement syndrome (SIS) is the most frequently recorded shoulder disorder. When conservative treatment of SIS fails, a subacromial decompression is warranted. However, the best moment of referral for surgery is not well defined. Both early and late referrals have disadvantages – unnecessary operations and smaller improvements in shoulder function, respectively. This paper describes the design of a new interdisciplinary treatment strategy for SIS (TRANSIT), which comprises rules to treat SIS in primary care and a well-defined moment of referral for surgery. METHODS/DESIGN: The effectiveness of an arthroscopic subacromial decompression versus usual medical care will be evaluated in a randomized controlled trial (RCT). Patients are eligible for inclusion when experiencing a recurrence of SIS within one year after a first episode of SIS which was successfully treated with a subacromial corticosteroid injection. After inclusion they will receive injection treatment again by their general practitioner. When, after this treatment, there is a second recurrence within a year post-injection, the participants will be randomized to either an arthroscopic subacromial decompression (intervention group) or continuation of usual medical care (control group). The latter will be performed by a general practitioner according to the Dutch National Guidelines for Shoulder Problems. At inclusion, at randomization and three, six and 12 months post-randomization an outcome assessment will take place. The primary outcome measure is the patient-reported Shoulder Disability Questionnaire. The secondary outcome measures include both disease-specific and generic measures, and an economic evaluation. Treatment effects will be compared for all measurement points by using a GLM repeated measures analyses. DISCUSSION: The rationale and design of an RCT comparing arthroscopic subacromial decompression with usual medical care for subacromial impingement syndrome are presented. The results of this study will improve insight into the best moment of referral for surgery for SIS

An 800-million-solar-mass black hole in a significantly neutral Universe at redshift 7.5

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120+0641 at z=7.09 has remained the only one known at z>7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10+092838.61 (hereafter J1342+0928) at redshift z=7.54. This quasar has a bolometric luminosity of 4e13 times the luminosity of the Sun and a black hole mass of 8e8 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old---just five percent of its current age---reinforces models of early black-hole growth that allow black holes with initial masses of more than about 1e4 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman alpha emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342+0928 is neutral. We derive a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.Comment: Updated to match the final journal versio

A Search for Extragalactic Fast Blue Optical Transients in ZTF and the Rate of AT2018cow-like Transients

We present a search for extragalactic fast blue optical transients (FBOTs) during Phase I of the Zwicky Transient Facility (ZTF). We identify 38 candidates with durations above half-maximum light 1 d < t1/2 < 12 d, of which 28 have blue (g-r<-0.2 mag) colors at peak light. Of the 38 transients (28 FBOTs), 19 (13) can be spectroscopically classified as core-collapse supernovae (SNe): 11 (8) H- or He-rich (Type II/IIb/Ib) SNe, 6 (4) interacting (Type IIn/Ibn) SNe, and 2 (1) H&He-poor (Type Ic/Ic-BL) SNe. Two FBOTs (published previously) had high-S/N predominantly featureless spectra and luminous radio emission: AT2018lug and AT2020xnd. Seven (five) did not have a definitive classification: AT 2020bdh showed tentative broad H$\alpha$ in emission, and AT 2020bot showed unidentified broad features and was 10 kpc offset from the center of an early-type galaxy. Ten (six) have no spectroscopic observations or redshift measurements. We present multiwavelength (radio, millimeter, and/or X-ray) observations for five FBOTs (three Type Ibn, one Type IIn/Ibn, one Type IIb). Additionally, we search radio-survey (VLA and ASKAP) data to set limits on the presence of radio emission for 22 of the transients. All X-ray and radio observations resulted in non-detections; we rule out AT2018cow-like X-ray and radio behavior for five FBOTs and more luminous emission (such as that seen in the Camel) for four additional FBOTs. We conclude that exotic transients similar to AT2018cow, the Koala, and the Camel represent a rare subset of FBOTs, and use ZTF's SN classification experiments to measure the rate to be at most 0.1% of the local core-collapse SN rate.Comment: Replaced following peer-review process. 46 pages, 20 figures. Accepted for publication in Ap

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

H I and CO in the circumstellar environment of the oxygen-rich AGB star RX Leporis

International audienceContext: Circumstellar shells around AGB stars are built over long periods of time that may reach several million years. They may therefore be extended over large sizes ( 1 pc, possibly more), and different complementary tracers are needed to describe their global properties. Aims: We set up a program to explore the properties of matter in the external parts of circumstellar shells around AGB stars and to relate them to those of the central sources (inner shells and stellar atmospheres). Methods: In the present work, we combined 21-cm H I and CO rotational line data obtained on an oxygen-rich semi-regular variable, RX Lep, to describe the global properties of its circumstellar environment. Results: With the SEST, we detected the CO(2-1) rotational line from RX Lep. The line profile is parabolic and implies an expansion velocity of 4.2 km s-1 and a mass-loss rate 1.7 × 10-7 M&sun; yr-1 (d = 137 pc). The H I line at 21 cm was detected with the Nançay Radiotelescope on the star position and at several offset positions. The linear shell size is relatively small, 0.1 pc, but we detect a trail extending southward to 0.5 pc. The line profiles are approximately Gaussian with an FWHM 3.8 km s-1 and interpreted with a model developed for the detached shell around the carbon-rich AGB star Y CVn. Our H I spectra are well-reproduced by assuming a constant outflow (dot{M} = 1.65 × 10-7 M&sun; yr-1) of 4 × 104 years duration, which has been slowed down by the external medium. The spatial offset of the H I source is consistent with the northward direction of the proper motion measured by Hipparcos, lending support to the presence of a trail resulting from the motion of the source through the ISM, as already suggested for Mira, RS Cnc, and other sources detected in H I . The source was also observed in SiO (3 mm) and OH (18 cm), but not detected. Conclusions: A detached shell, similar to the one around Y CVn, was discovered in H I around RX Lep. We also found evidence of an extension in the direction opposite to the star proper motion. The properties of the external parts of circumstellar shells around AGB stars should be dominated by the interaction between stellar outflows and external matter for oxygen-rich, as well as for carbon-rich, sources, and the 21-cm H I line provides a very useful tracer of these regions