ABSTRACT
We present observations of ASASSN-19dj, a nearby tidal disruption event (TDE) discovered in the post-starburst galaxy KUG 0810+227 by the All-Sky Automated Survey for Supernovae (ASAS-SN) at ...a distance of d ≃ 98 Mpc. We observed ASASSN-19dj from −21 to 392 d relative to peak ultraviolet (UV)/optical emission using high-cadence, multiwavelength spectroscopy and photometry. From the ASAS-SN g-band data, we determine that the TDE began to brighten on 2019 February 6.8 and for the first 16 d the rise was consistent with a flux ∝t2 power law. ASASSN-19dj peaked in the UV/optical on 2019 March 6.5 (MJD = 58548.5) at a bolometric luminosity of L = (6.2 ± 0.2) × 1044 erg s−1. Initially remaining roughly constant in X-rays and slowly fading in the UV/optical, the X-ray flux increased by over an order of magnitude ∼225 d after peak, resulting from the expansion of the X-ray emitting region. The late-time X-ray emission is well fitted by a blackbody with an effective radius of ∼1 × 1012 cm and a temperature of ∼6 × 105 K. The X-ray hardness ratio becomes softer after brightening and then returns to a harder state as the X-rays fade. Analysis of Catalina Real-Time Transient Survey images reveals a nuclear outburst roughly 14.5 yr earlier with a smooth decline and a luminosity of LV ≥ 1.4 × 1043 erg s−1, although the nature of the flare is unknown. ASASSN-19dj occurred in the most extreme post-starburst galaxy yet to host a TDE, with Lick HδA = 7.67 ± 0.17 Å.
We report the first plausible optical electromagnetic counterpart to a (candidate) binary black hole merger. Detected by the Zwicky Transient Facility, the electromagnetic flare is consistent with ...expectations for a kicked binary black hole merger in the accretion disk of an active galactic nucleus B. McKernan, K. E. S. Ford, I. Bartoset al., Astrophys. J. Lett.884, L50 (2019) and is unlikely <O(0.01%)) due to intrinsic variability of this source. The lack of color evolution implies that it is not a supernova and instead is strongly suggestive of a constant temperature shock. Other false-positive events, such as microlensing ora tidal disruption event, are ruled out or constrained to be <O(0.1%). If the flare is associated withS190521g, we find plausible values of total mass M(BBH) ∼ 100 Mꙩ, kick velocity v(k) ∼ 200 km/s at θ ∼ 60° in a disk with aspect ratio H/a ∼ 0.01(i.e., disk height H at radius a) and gas density ρ ∼ 10^(−10)g/cu.cm. The merger could have occurred at a disk migration trap (a ∼ 700 r(g); r(g) ≡ GM(SMBH)/sq.c, where M(SMBH) is the mass of the active galactic nucleus supermassive black hole). The combination of parameters implies a significant spin for at least one of the black holes in S190521g. The timing of our spectroscopy prevents useful constraints on broad-line asymmetry due to an off-center flare. We predict a repeat flare in this source due to a reencountering with the disk in ∼ 1.6 yr(M(SMBH)/10^(8) Mꙩ)(a/10^(3)r(g))^(3/2).
Abstract
We derive the low-redshift galaxy stellar mass function (GSMF), inclusive of dust corrections, for the equatorial Galaxy And Mass Assembly (GAMA) data set covering 180 deg2. We construct the ...mass function using a density-corrected maximum volume method, using masses corrected for the impact of optically thick and thin dust. We explore the galactic bivariate brightness plane (M
⋆–μ), demonstrating that surface brightness effects do not systematically bias our mass function measurement above 107.5 M⊙. The galaxy distribution in the M–μ plane appears well bounded, indicating that no substantial population of massive but diffuse or highly compact galaxies are systematically missed due to the GAMA selection criteria. The GSMF is fitted with a double Schechter function, with
$\mathcal {M}^\star =10^{10.78\pm 0.01\pm 0.20}\,\mathrm{M}_{\odot }$
,
$\phi ^\star _1=(2.93\pm 0.40)\times 10^{-3}\,h_{70}^3$
Mpc−3, α1 = −0.62 ± 0.03 ± 0.15,
$\phi ^\star _2=(0.63\pm 0.10)\times 10^{-3}\,h_{70}^3$
Mpc−3 and α2 = −1.50 ± 0.01 ± 0.15. We find the equivalent faint end slope as previously estimated using the GAMA-I sample, although we find a higher value of
$\mathcal {M}^\star$
. Using the full GAMA-II sample, we are able to fit the mass function to masses as low as 107.5 M⊙, and assess limits to 106.5 M⊙. Combining GAMA-II with data from G10-COSMOS, we are able to comment qualitatively on the shape of the GSMF down to masses as low as 106 M⊙. Beyond the well-known upturn seen in the GSMF at 109.5, the distribution appears to maintain a single power-law slope from 109 to 106.5. We calculate the stellar mass density parameter given our best-estimate GSMF, finding
$\Omega _\star = 1.66^{+0.24}_{-0.23}\pm 0.97 \,h^{-1}_{70} \times 10^{-3}$
, inclusive of random and systematic uncertainties.
Conjunctivitis in dupilumab clinical trials Akinlade, B.; Guttman‐Yassky, E.; Bruin‐Weller, M. ...
British journal of dermatology (1951),
September 2019, Letnik:
181, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
Background
Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis ...(AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo.
Objectives
To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials.
Methods
We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47).
Results
In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis.
Conclusions
Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study.
What's already known about this topic?
Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).
In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.
Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.
Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis.
What does this study add?
This analysis confirms and extends the results of the individual clinical trials.
Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.
Patients who responded well to dupilumab had reduced incidence of conjunctivitis.
Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD.
Linked Editorial: Chia‐Yu Chu. Br J Dermatol 2019; 181:436–437.
Plain language summary available online
Respond to this article
Supermassive black hole binaries (SMBHBs) at sub-parsec separations should be common in galactic nuclei, as a result of frequent galaxy mergers. Hydrodynamical simulations of circum-binary discs ...predict strong periodic modulation of the mass accretion rate on time-scales comparable to the orbital period of the binary. As a result, SMBHBs may be recognized by the periodic modulation of their brightness. We conducted a statistical search for periodic variability in a sample of 35 383 spectroscopically confirmed quasars in the photometric data base of the Palomar Transient Factory (PTF). We analysed Lomb–Scargle periodograms and assessed the significance of our findings by modelling each individual quasar's variability as a damped random walk (DRW). We identified 50 quasars with significant periodicity beyond the DRW model, typically with short periods of a few hundred days. We find 33 of these to remain significant after a re-analysis of their periodograms including additional optical data from the intermediate-PTF and the Catalina Real-Time Transient Survey. Assuming that the observed periods correspond to the redshifted orbital periods of SMBHBs, we conclude that our findings are consistent with a population of unequal-mass SMBHBs, with a typical mass ratio as low as q ≡ M
2/M
1 ≈ 0.01.
Studies have shown that rates of liver disease are higher in persons who are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) than they are in persons with HCV alone, ...but estimates of risk vary widely and are based on data for dissimilar patient populations. We performed a meta-analysis to quantify the effect of HIV coinfection on progressive liver disease in persons with HCV. Eight studies were identified that included outcomes of histological cirrhosis or decompensated liver disease. These studies yielded a combined adjusted relative risk (RR) of 2.92 (95% confidence interval CI, 1.70-5.01). Of note, studies that examined decompensated liver disease had a combined RR of 6.14 (95% CI, 2.86-13.20), whereas studies that examined histological cirrhosis had a pooled RR of 2.07 (95% CI, 1.40-3.07). There is a significantly elevated RR of severe liver disease in persons who are coinfected with HIV and HCV. This has important implications for timely diagnosis and consideration of treatment in coinfected persons.
Objective
Standard surgical treatment of advanced-stage ovarian carcinoma with electrosurgery cannot always result in complete cytoreductive surgery (CRS), especially when many small metastases are ...found on the mesentery and intestinal surface. We investigated whether adjuvant use of a neutral argon plasma device can help increase the complete cytoreduction rate.
Patients and Methods
327 patients with FIGO stage IIIB–IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were randomized to either surgery with neutral argon plasma (PlasmaJet) (intervention) or without PlasmaJet (control group). The primary outcome was the percentage of complete CRS. The secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30-day morbidity, and quality of life (QoL).
Results
Complete CRS was achieved in 119 patients (75.8%) in the intervention group and 115 patients (67.6%) in the control group (risk difference (RD) 8.2%, 95% confidence interval (CI) –0.021 to 0.181;
P
= 0.131). In a per-protocol analysis excluding patients with unresectable disease, complete CRS was obtained in 85.6% in the intervention group and 71.5% in the control group (RD 14.1%, 95% CI 0.042 to 0.235;
P
= 0.005). Patient-reported QoL at 6 months after surgery differed between groups in favor of PlasmaJet surgery (95% CI 0.455–8.350;
P
= 0.029). Other secondary outcomes did not differ significantly.
Conclusions
Adjuvant use of PlasmaJet during CRS for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete CRS in patients with resectable disease and higher QoL at 6 months after surgery. (Funded by ZonMw, Trial Register NL62035.078.17.)
Trial Registration
Approved by the Medical Ethics Review Board of the Erasmus University Medical Center Rotterdam, the Netherlands, NL62035.078.17 on 20-11-2017. Recruitment started on 30-1-2018.
Premise of research. The origin of land plants catalyzed key changes in Earth’s atmosphere and biota. Microbial associations likely nurtured earliest plants and influenced their biogeochemical roles. ...Because angiosperm and animal microbiomes—bacteria, archaea, microbial eukaryotes, and genes that promote host survival—are known to display lineage effects, we hypothesized that microbiomes of early-diverging modern bryophytes and phylogenetically closely related green algae might likewise reveal commonalities reflecting ancestral traits.
Methodology. New metagenomic sequence data were obtained for the late-diverging streptophyte algae Chaetosphaeridium globosum and Coleochaete pulvinata and the liverwort Conocephalum conicum, representing early-diverging land plants. New 16S rDNA amplicon sequences were acquired for the charalean Nitella tenuissima. Sequence data were used to infer bacterial genera and fungi for comparisons among streptophyte microbiota and with our published microbiome data for the outgroup chlorophyte Cladophora. To enhance evolutionary signal, taxa were sampled in the same time frame and from geographically close locales. Streptophyte metagenomic data were also probed for protein markers of significant physiological and biogeochemical functions: NifH indicating nitrogen fixation, particulate MMo indicating methane oxidation, and vitamin B12 (cobalamin) indicating biosynthetic pathway enzymes.
Pivotal results. Microbiota of studied streptophytes consistently included diverse N-fixing cyanobacteria and/or Rhizobiales, as well as methanotrophs and early-diverging fungi, and were more similar to each other than to Cladophora microbiota. Streptophyte metagenomic data indicated diverse nifH (nitrogen fixation) and pMMo (methane oxidation) marker sequences and vitamin B12 pathway genes. Glomalean fungi occurred with Conocephalum, consistent with field studies of modern liverworts and microfossil evidence for co-occurrence of glomaleans and early land plants.
Conclusions. A suite of N fixers, methanotrophs, cobalamin producers, and early-diverging fungi was consistently associated with modern streptophyte algae and bryophytes studied, suggesting features of early land plants that have played significant, previously unrecognized roles in global nitrogen and carbon cycling for hundreds of millions of years.
To identify and synthesize studies reporting modifiable barriers/enablers associated with retinopathy screening attendance in people with Type 1 or Type 2 diabetes, and to identify those most likely ...to influence attendance.
We searched MEDLINE, EMBASE, PsycINFO, Cochrane Library and the 'grey literature' for quantitative and qualitative studies to February 2017. Data (i.e. participant quotations, interpretive summaries, survey results) reporting barriers/enablers were extracted and deductively coded into domains from the Theoretical Domains Framework; with domains representing categories of theoretical barriers/enablers proposed to mediate behaviour change. Inductive thematic analysis was conducted within domains to describe the role each domain plays in facilitating or hindering screening attendance. Domains that were more frequently coded and for which more themes were generated were judged more likely to influence attendance.
Sixty-nine primary studies were included. We identified six theoretical domains 'environmental context and resources' (75% of included studies), 'social influences' (51%), 'knowledge' (51%), 'memory, attention, decision processes' (50%), 'beliefs about consequences' (38%) and 'emotions' (33%) as the key mediators of diabetic retinopathy screening attendance. Examples of barriers populating these domains included inaccurate diabetic registers and confusion between routine eye care and retinopathy screening. Recommendations by healthcare professionals and community-level media coverage acted as enablers.
Across a variety of contexts, we found common barriers to and enablers of retinopathy screening that could be targeted in interventions aiming to increase screening attendance.
Summary
Background
Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective ...in all patients with atopic dermatitis, and side‐effects limit its use. Dupilumab, a fully human anti‐interleukin 4 receptor‐alpha monoclonal antibody, inhibits signaling of IL‐4 and IL‐13, key drivers of Type 2/Th2‐mediated inflammation, and is approved in the U.S.A. and the European Union for the treatment of inadequately‐controlled moderate‐to‐severe atopic dermatitis in adults.
Objectives
To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic dermatitis with inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable.
Methods
In this 16‐week, double‐blind, randomized, placebo‐controlled, phase III trial, patients were randomized 1 : 1 : 1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo. All received concomitant medium‐potency TCS from Week −2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS.
Results
In total, 390 patients were screened, 325 were randomized, and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the placebo + TCS group (primary end point) (59·1% and 62·6% vs. 29·6%, respectively; P < 0·001 vs. placebo + TCS, both doses). Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS and placebo + TCS groups: 69·1%, 72·0% and 69·4%, respectively) and serious adverse events (1·8%, 1·9% and 1·9%, respectively). Conjunctivitis was more frequent with dupilumab + TCS; skin infections were more frequent with placebo + TCS.
Conclusions
Dupilumab + TCS significantly improved signs and symptoms of atopic dermatitis and QoL in adults with a history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified.
What's already known about this topic?
Patients with atopic dermatitis that is inadequately controlled with topical therapy have few systemic treatment options.
Ciclosporin A (CsA) is a systemic immunosuppressant approved for atopic dermatitis in most European countries and Japan, but not all patients respond, and side‐effects limit its use.
Dupilumab (monoclonal antibody against interleukin‐4 receptor‐alpha) with/without topical corticosteroids (TCS) is approved in the U.S.A. and the European Union for the treatment of adults with inadequately‐controlled moderate‐to‐severe atopic dermatitis.
What does this study add?
In this 16‐week trial in adults with atopic dermatitis and history of inadequate response or intolerance to CsA, or for whom CsA treatment was medically inadvisable, dupilumab administered weekly or every 2 weeks with concomitant TCS significantly improved signs and symptoms and quality of life, with no new safety signals.
These data support the use of dupilumab in this difficult‐to‐treat population.
Linked Editorial: Schmitt. Br J Dermatol 2018; 178:992–993.
Linked Letter: Thyssen. Br J Dermatol 2018; 178:1220.
Plain language summary available online
Respond to this article
PDF
