We report the first results of AS2UDS, an 870 m continuum survey with the Atacama Large Millimeter/Submillimeter Array (ALMA) of a total area of ∼50 arcmin2 comprising a complete sample of 716 ...submillimeter sources drawn from the SCUBA-2 Cosmology Legacy Survey (S2CLS) map of the UKIDSS/UDS field. The S2CLS parent sample covers a 0.96 degree2 field at 850 = 0.90 0.05 mJy beam−1. Our deep, high-resolution ALMA observations with 870 ∼ 0.25 mJy and a 0 15-0 30 FWHM synthesized beam, provide precise locations for 695 submillimeter galaxies (SMGs) responsible for the submillimeter emission corresponding to 606 sources in the low-resolution, single-dish map. We measure the number counts of SMGs brighter than S870 ≥ 4 mJy, free from the effects of blending and show that the normalization of the counts falls by 28% 2% in comparison with the SCUBA-2 published counts, but that the shape remains unchanged. We determine that 44 − 14 + 16 % of the brighter single-dish sources with S850 ≥ 9 mJy consist of a blend of two or more ALMA-detectable SMGs brighter than S870 ∼ 1 mJy (corresponding to a galaxy with a total-infrared luminosity of LIR 1012 L ), in comparison with 28% 2% for the single-dish sources at S850 ≥ 5 mJy. Using the 46 single-dish submillimeter sources that contain two or more ALMA-detected SMGs with photometric redshifts, we show that there is a significant statistical excess of pairs of SMGs with similar redshifts (<1% probability of occurring by chance), suggesting that at least 30% of these blends arise from physically associated pairs of SMGs.
Abstract
We present a new exploration of the cosmic star formation history and dust obscuration in massive galaxies at redshifts 0.5 < z < 6. We utilize the deepest 450- and 850-μm imaging from ...SCUBA-2 CLS, covering 230 arcmin2 in the AEGIS, COSMOS and UDS fields, together with 100–250 μm imaging from Herschel. We demonstrate the capability of the t-phot deconfusion code to reach below the confusion limit, using multiwavelength prior catalogues from CANDELS/3D-HST. By combining IR and UV data, we measure the relationship between total star formation rate (SFR) and stellar mass up to z ∼ 5, indicating that UV-derived dust corrections underestimate the SFR in massive galaxies. We investigate the relationship between obscuration and the UV slope (the IRX–β relation) in our sample, which is similar to that of low-redshift starburst galaxies, although it deviates at high stellar masses. Our data provide new measurements of the total SFR density (SFRD) in $M_{\ast }>10^{10}\,\textrm{M}_{\odot }$ galaxies at 0.5 < z < 6. This is dominated by obscured star formation by a factor of >10. One third of this is accounted for by 450-μm-detected sources, while one-fifth is attributed to UV-luminous sources (brighter than $L_{\rm UV}^\ast$), although even these are largely obscured. By extrapolating our results to include all stellar masses, we estimate a total SFRD that is in good agreement with previous results from IR and UV data at z ≲ 3, and from UV-only data at z ∼ 5. The cosmic star formation history undergoes a transition at z ∼ 3–4, as predominantly unobscured growth in the early Universe is overtaken by obscured star formation, driven by the build-up of the most massive galaxies during the peak of cosmic assembly.
We present a multi-wavelength analysis of 52 submillimeter galaxies (SMGs), identified using ALMA 870 m continuum imaging in a pilot program to precisely locate bright SCUBA-2-selected submillimeter ...sources in the UKIDSS Ultra Deep Survey (UDS) field. Using the available deep (especially near-infrared) panoramic imaging of the UDS field at optical-to-radio wavelengths we characterize key properties of the SMG population. The median photometric redshift of the bright ALMA/SCUBA-2 UDS (AS2UDS) SMGs that are detected in a sufficient number of wavebands to derive a robust photometric redshift is z = 2.65 0.13. However, similar to previous studies, 27% of the SMGs are too faint at optical-to-near-infrared wavelengths to derive a reliable photometric redshift. Assuming that these SMGs lie at z 3 raises the median redshift of the full sample to z = 2.9 0.2. A subset of 23 unlensed, bright AS2UDS SMGs have sizes measured from resolved imaging of their rest-frame far-infrared emission. We show that the extent and luminosity of the far-infrared emission are consistent with the dust emission arising from regions that are, on average, optically thick at a wavelength of (1 dispersion of 55-90 m). Using the dust masses derived from our optically thick spectral energy distribution models, we determine that these galaxies have a median hydrogen column density of NH = 9.8 × 1023 cm−2, or a corresponding median V-band obscuration of Av = 540 mag, averaged along the line of sight to the source of their rest-frame ∼200 m emission. We discuss the implications of this extreme attenuation by dust for the multi-wavelength study of dusty starbursts and reddening-sensitive tracers of star formation.
We present sensitive 850 m imaging of the Cosmological Evolution Survey (COSMOS) field using 640 hr of new and archival observations taken with SCUBA-2 at the East Asian Observatory's James Clerk ...Maxwell Telescope. The SCUBA-2 COSMOS survey (S2COSMOS) achieves a median noise level of 850 m = 1.2 mJy beam−1 over an area of 1.6 sq. degree (main; Hubble Space Telescope/Advanced Camera for Surveys footprint), and 850 m = 1.7 mJy beam−1 over an additional 1 sq. degree of supplementary (supp) coverage. We present a catalog of 1020 and 127 sources detected at a significance level of >4 and >4.3 in the main and supp regions, respectively, corresponding to a uniform 2% false-detection rate. We construct the single-dish 850 m number counts at S850 > 2 mJy and show that these S2COSMOS counts are in agreement with previous single-dish surveys, demonstrating that degree-scale fields are sufficient to overcome the effects of cosmic variance in the S850 = 2-10 mJy population. To investigate the properties of the galaxies identified by S2COSMOS sources we measure the surface density of near-infrared-selected galaxies around their positions and identify an average excess of 2.0 0.2 galaxies within a 13″ radius (∼100 kpc at z ∼ 2). The bulk of these galaxies represent near-infrared-selected submillimeter galaxies and/or spatially correlated sources and lie at a median photometric redshift of z = 2.0 0.1. Finally, we perform a stacking analysis at submillimeter and far-infrared wavelengths of stellar-mass-selected galaxies (M = 1010-1012 M ) from z = 0-4, obtaining high-significance detections at 850 m in all subsets (signal-to-noise ratio, S/N = 4-30), and investigate the relation between far-infrared luminosity, stellar mass, and the peak wavelength of the dust spectral energy distribution. The publication of this survey adds a new deep, uniform submillimeter layer to the wavelength coverage of this well-studied COSMOS field.
Summary Background The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed ...first-trimester pregnancies of women from the Thai–Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. Methods We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. Findings Of 48 426 pregnant women, 17 613 (36%) met the inclusion criteria: 16 668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2·70, 95% CI 2·04–3·59) and symptomatic malaria (3·99, 3·10–5·13), and were similar for Plasmodium falciparum and Plasmodium vivax . Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3·63, 95% CI 1·15–11·46) and parasitaemia (1·49, 1·25–1·78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0·86, 95% CI 0·81–0·91). The risk of miscarriage was similar for women treated with chloroquine (92 26% of 354), quinine (95 27%) of 355), or artesunate (20 31% of 64; p=0·71). Adverse effects related to antimalarial treatment were not observed. Interpretation A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage. No additional toxic effects associated with artesunate treatment occurred in early pregnancy. Prospective studies should now be done to assess the safety and efficacy of artemisinin combination treatments in early pregnancy. Funding Wellcome Trust and Bill & Melinda Gates Foundation.
We report the results of a search for serendipitous C ii 157.74 m emitters at z 4.4-4.7 using the Atacama Large Millimeter/submillimeter Array (ALMA). The search exploits the AS2UDS continuum survey, ...which covers ∼50 arcmin2 of the sky toward 695 luminous (S870 1 mJy) submillimeter galaxies (SMGs), selected from the SCUBA-2 Cosmology Legacy Survey 0.96 deg2 Ultra Deep Survey (UDS) field. We detect 10 candidate line emitters, with an expected false detection rate of 10%. All of these line emitters correspond to 870 m continuum-detected sources in AS2UDS. The emission lines in two emitters appear to be high-J CO, but the remainder have multi-wavelength properties consistent with C ii from z 4.5 galaxies. Using our sample, we place a lower limit of on the space density of luminous (LIR 1013 ) SMGs at z = 4.40-4.66, suggesting % of SMGs with mJy lie at 4 < z < 5. From stacking the high-resolution (∼0 15 full-width half maximum) ALMA 870 m imaging, we show that the C ii line emission is more extended than the continuum dust emission, with an average effective radius for the C ii of kpc, compared to re = 1.0 0.1 kpc for the continuum (rest-frame 160 m). By fitting the far-infrared photometry for these galaxies from 100 to 870 m, we show that SMGs at z ∼ 4.5 have a median dust temperature of Td = 55 4 K. This is systematically warmer than 870 m selected SMGs at z 2, which typically have temperatures around 35 K. These z 4.5 SMGs display a steeper trend in the luminosity-temperature plane than z ≤ 2 SMGs. We discuss the implications of this result in terms of the selection biases of high-redshift starbursts in far-infrared/submillimeter surveys.
We analyze the multifrequency radio spectral properties of 41 6 GHz-detected Atacama Large Millimeter/submillimeter Array (ALMA)-identified, submillimeter galaxies (SMGs), observed at 610 MHz, 1.4 ...GHz, and 6 GHz with the Giant Metrewave Radio Telescope and the Very Large Array. Combining high-resolution (∼0 5) 6 GHz radio and ALMA 870 m imaging (tracing rest frame ∼20 GHz, and ∼250 m dust continuum), we study the far-infrared/radio correlation via the logarithmic flux ratio qIR, measuring for our sample. We show that the high-frequency radio sizes of SMGs are ∼1.9 0.4× (∼2-3 kpc) larger than those of the cool dust emission, and find evidence for a subset of our sources being extended on ∼10 kpc scales at 1.4 GHz. By combining radio flux densities measured at three frequencies, we can move beyond simple linear fits to the radio spectra of high-redshift star-forming galaxies, and search for spectral curvature, which has been observed in local starburst galaxies. At least a quarter (10/41) of our sample shows evidence of a spectral break, with a median , but -a high-frequency flux deficit relative to simple extrapolations from the low-frequency data. We explore this result within this subset of sources in the context of age-related synchrotron losses, showing that a combination of weak magnetic fields (B ∼ 35 G) and young ages (tSB ∼ 40-80 Myr) for the central starburst can reproduce the observed spectral break. Assuming these represent evolved (but ongoing) starbursts, and we are observing these systems roughly halfway through their current episode of star formation, this implies starburst durations of 100 Myr, in reasonable agreement with estimates derived via gas depletion timescales.
Summary
Background
Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin‐13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II ...studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms.
Objectives
To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate‐to‐severe AD who had an inadequate response to topical treatments.
Methods
In two 52‐week, randomized, double‐blind, placebo‐controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate‐to‐severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator’s Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885.
Results
At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 difference 8·6%, 95% confidence interval (CI) 4·1–13·1; P = 0·002 and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8–16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5–17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8–27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient‐Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16‐week initial period.
Conclusions
Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.
What is already known about this topic?
Atopic dermatitis (AD) is a chronic interleukin (IL)‐13‐mediated disease.
There is a need for safe and effective long‐term treatment options for AD.
Tralokinumab is a fully human monoclonal antibody that binds specifically to IL‐13 with high affinity, thereby preventing receptor interaction and subsequent downstream signalling.
Tralokinumab combined with topical corticosteroids showed early and sustained efficacy and safety in a 12‐week, phase IIb trial in moderate‐to‐severe AD.
What does this study add?
These are the first pivotal phase III trials demonstrating that by specifically targeting IL‐13 alone, patients can achieve significant improvements in AD signs and symptoms and quality of life, and maintain these improvements over time without the requirement for topical corticosteroids.
These trials provide evidence that tralokinumab offers a long‐term, well‐tolerated treatment option for patients with moderate‐to‐severe AD.
Linked Comment: Morra and Drucker. Br J Dermatol 2021; 184:386–387.
Plain language summary available online
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
ABSTRACT
We analyse 870 $\mu$m Atacama Large Millimetre Array (ALMA) dust continuum detections of 41 canonically selected $z$ ≃ 3 Lyman-break galaxies (LBGs), as well as 209 ALMA-undetected LBGs, in ...follow-up of SCUBA-2 mapping of the UKIDSS Ultra Deep Survey (UDS) field. We find that our ALMA-bright LBGs lie significantly off the local IRX-beta relation and have relatively bluer rest-frame UV slopes (as parametrized by β), given their high values of the ‘infrared excess’ (IRX ≡ LIR/LUV), relative to the average ‘local’ IRX-β relation. We attribute this finding in part to the young ages of the underlying stellar populations but we find that the main reason behind the unusually blue UV slopes are the relatively shallow slopes of the corresponding dust attenuation curves. We show that, when stellar masses, M*, are being established via SED fitting, it is absolutely crucial to allow the attenuation curves to vary (rather than fixing it on Calzetti-like law), where we find that the inappropriate curves may underestimate the resulting stellar masses by a factor of ≃2–3× on average. In addition, we find these LBGs to have relatively high specific star-formation rates (sSFRs), dominated by the dust component, as quantified via the fraction of obscured star formation $(f_{\rm obs}\equiv {\rm SFR_{\rm IR}/{\rm SFR}_{\rm UV+IR}})$. We conclude that the ALMA-bright LBGs are, by selection, massive galaxies undergoing a burst of a star formation (large sSFRs, driven, for example, by secular or merger processes), with a likely geometrical disconnection of the dust and stars, responsible for producing shallow dust attenuation curves.
PDF
