The Type Ia supernova (SN Ia) rate, when compared to the cosmic star formation history (SFH), can be used to derive the delay-time distribution (DTD; the hypothetical SN Ia rate versus time following ...a brief burst of star formation) of SNe Ia, which can distinguish among progenitor models. We present the results of a supernova (SN) survey in the Subaru Deep Field (SDF). Over a period of 3 years, we have observed the SDF on four independent epochs with Suprime-Cam on the Subaru 8.2-m telescope, with two nights of exposure per epoch, in the R, i′and z′ bands. We have discovered 150 SNe out to redshift z≈ 2. Using 11 photometric bands from the observer-frame far-ultraviolet to the near-infrared, we derive photometric redshifts for the SN host galaxies (for 24 we also have spectroscopic redshifts). This information is combined with the SN photometry to determine the type and redshift distribution of the SN sample. Our final sample includes 28 SNe Ia in the range 1.0 < z < 1.5 and 10 in the range 1.5 < z < 2.0. As our survey is largely insensitive to core-collapse SNe (CC SNe) at z > 1, most of the events found in this range are likely SNe Ia. Our SN Ia rate measurements are consistent with those derived from the Hubble Space Telescope (HST) Great Observatories Origins Deep Survey (GOODS) sample, but the overall uncertainty of our 1.5 < z < 2.0 measurement is a factor of 2 smaller, of 35-50 per cent. Based on this sample, we find that the SN Ia rate evolution levels off at 1.0 < z < 2.0, but shows no sign of declining. Combining our SN Ia rate measurements and those from the literature, and comparing to a wide range of possible SFHs, the best-fitting DTD (with a reduced χ2= 0.7) is a power law of the form Ψ(t) ∝t
β, with index β=−1.1 ± 0.1 (statistical) ±0.17 (systematic). This result is consistent with other recent DTD measurements at various redshifts and environments, and is in agreement with a generic prediction of the double-degenerate progenitor scenario for SNe Ia. Most single-degenerate models predict different DTDs. By combining the contribution from CC SNe, based on the wide range of SFHs, with that from SNe Ia, calculated with the best-fitting DTD, we predict that the mean present-day cosmic iron abundance is in the range Z
Fe= (0.09-0.37) ZFe, ⊙. We further predict that the high-z SN searches now beginning with HST will discover 2-11 SNe Ia at z > 2.
The recent availability of multiple Clostridium botulinum genomic sequences has initiated a new genomics era that strengthens our understanding of the bacterial species that produce botulinum ...neurotoxins (BoNTs). Analysis of the genomes has reinforced the historical Group I–VI designations and provided evidence that the bont genes can be located within the chromosome, phage or plasmids. The sequences provide the opportunity to examine closely the variation among the toxin genes, the composition and organization of the toxin complex, the regions flanking the toxin complex and the location of the toxin within different bacterial strains. These comparisons provide evidence of horizontal gene transfer and site-specific insertion and recombination events that have contributed to the variation observed among the neurotoxins. Here, examples that have contributed to the variation observed in serotypes A-H strains are presented to illustrate the mechanisms that have contributed to their variation.
•Genetic diversity of botulinum neurotoxin-producing clostridia is discussed.•Toxin subtypes are compared and delineated.•Mechanisms for the movement of toxin genes are explained.•Toxin cluster types are illustrated.•Toxin locations within genomes are highlighted.
We present Searches After Gravitational-waves Using ARizona Observatories (SAGUARO), a comprehensive effort dedicated to the discovery and characterization of optical counterparts to ...gravitational-wave (GW) events. SAGUARO utilizes ground-based facilities ranging from 1.5 to 10 m in diameter, located primarily in the Northern Hemisphere. We provide an overview of SAGUARO's telescopic resources, its pipeline for transient detection, and its database for candidate visualization. We describe SAGUARO's discovery component, which utilizes the 5 deg2 field of view optical imager on the Mt. Lemmon 1.5 m telescope, reaching limits of 21.3 AB mag while rapidly tiling large areas. We also describe the follow-up component of SAGUARO, used for rapid vetting and monitoring of optical candidates. With the onset of Advanced LIGO/Virgo's third observing run, we present results from the first three SAGUARO searches following the GW events S190408an, S190425z and S190426c, which serve as a valuable proof-of-concept of SAGUARO. We triggered and searched 15, 60, and 60 deg2 respectively, 17.6, 1.4, and 41.8 hr after the initial GW alerts. We covered 7.8%, 3.0%, and 5.1% of the total probability within the GW event localizations, reaching 3 limits of 19.8, 21.3, and 20.8 AB mag, respectively. Although no viable counterparts associated with these events were found, we recovered six known transients and ruled out five potential candidates. We also present Large Binocular Telescope spectroscopy of PS19eq/SN2019ebq, a promising kilonova candidate that was later determined to be a supernova. With the ability to tile large areas and conduct detailed follow-up, SAGUARO represents a significant addition to GW counterpart searches.
For patients with a reduced left ventricular ejection fraction (LVEF) heart failure with reduced ejection fraction (HFrEF) and iron deficiency, administration of intravenous iron improves symptoms, ...exercise capacity and may in the following 12 months, reduce hospitalisations for heart failure. The Effectiveness of
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ent versus standard care in p
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ts with heart failure and iron deficiency (IRONMAN) trial evaluated whether the benefits of intravenous iron persist in the longer term and impact on morbidity and mortality.
IRONMAN is a prospective, randomised, open-label, blinded endpoint (PROBE) event-driven trial. Patients aged ≥18 years with HFrEF (LVEF ≤45%) and evidence of iron deficiency (ferritin <100 µg/L and/or TSAT <20%) were enrolled if they had either a current or recent hospitalisation for heart failure or elevated plasma concentrations of a natriuretic peptide. Participants were randomised to receive, or not to receive, intravenous ferric derisomaltose in addition to guideline-recommended therapy for HFrEF. Every 4 months, intravenous iron was administered if either ferritin was <100 µg/L or, provided ferritin was ≤400 µg/L, TSAT was <25%. The primary endpoint is a composite of total hospitalisations for heart failure and cardiovascular death. Hospitalisation and deaths due to infection are safety endpoints.
Trial recruitment was completed across 70 UK hospital sites in October 2021. Participants were followed until the end of March 2022. We plan to report the results by November 2022.
IRONMAN will determine whether repeated doses of intravenous ferric derisomaltose are beneficial and safe for the long-term treatment of a broad range of patients with HFrEF and iron deficiency.
NCT02642562.
Large samples of high-redshift supernovae (SNe) are potentially powerful probes of cosmic star formation, metal enrichment and SN physics. We present initial results from a new deep SN survey, based ...on re-imaging in the R, i′, z′ bands, of the 0.25 deg2 Subaru Deep Field (SDF), with the 8.2-m Subaru telescope and Suprime-Cam. In a single new epoch consisting of two nights of observations, we have discovered 33 candidate SNe, down to a z′-band magnitude of 26.3 (AB). We have measured the photometric redshifts of the SN host galaxies, obtained Keck spectroscopic redshifts for 17 of the host galaxies and classified the SNe using the Bayesian photometric algorithm of Poznanski et al. that relies on template matching. After correcting for biases in the classification, 55 per cent of our sample consists of Type Ia SNe and 45 per cent of core-collapse SNe. The redshift distribution of the SNe Ia reaches z≈ 1.6, with a median of z≈ 1.2. The core-collapse SNe reach z≈ 1.0, with a median of z≈ 0.5. Our SN sample is comparable to the Hubble Space Telescope/Great Observatories Origins Deep Survey (GOODS) sample in both size and redshift range. The redshift distributions of the SNe in the SDF and in GOODS are consistent, but there is a trend (which requires confirmation using a larger sample) for more high-z SNe Ia in the SDF. This trend is also apparent when comparing the SN Ia rates we derive to those based on GOODS data. Our results suggest a fairly constant rate at high redshift that could be tracking the star formation rate. Additional epochs on this field, already being obtained, will enlarge our SN sample to the hundreds, and determine whether or not there is a decline in the SN Ia rate at z≳ 1.
Summary
Background
Inhalational antigen tolerance typically protects against the development of allergic airway disease but may be overcome to induce allergic sensitization preceding the development ...of asthma.
Objectives
We examined in vivo whether pre‐existing inhalational antigen tolerance could be overcome by activation of the transcription factor NF‐κB in conducting airway epithelial cells, and used a combination of in vivo and in vitro approaches to examine the mechanisms involved.
Methods
Wild‐type and transgenic mice capable of expressing constitutively active IκB kinase β (CAIKKβ) in airway epithelium were tolerized to inhaled ovalbumin. Twenty‐eight days later, the transgene was transiently expressed and mice were exposed to inhaled OVA on Day 30 in an attempt to overcome inhalational tolerance.
Results
Following ovalbumin challenge on days 40–42, CAIKKβ mice in which the transgene had been activated exhibited characteristic features of allergic airway disease, including airway eosinophilia and methacholine hyper‐responsiveness. Increases in the CD103+ and CD11bHI lung dendritic cell populations were present in CAIKKβ mice on Day 31. Bronchoalveolar lavage from mice expressing CAIKKβ mice induced CD4+ T cells to secrete TH2 and TH17 cytokines, an effect that required IL‐4 and IL‐1 signalling, respectively. CAIKKβ mice on Dox demonstrated increased numbers of innate lymphoid type 2 cells (ILC2) in the lung, which also exhibited elevated mRNA expression of the TH2‐polarizing cytokine IL‐4. Finally, airway epithelial NF‐kB activation induced allergic sensitization in CAIKKβ mice on Dox that required IL‐4 and IL‐1 signalling in vivo.
Conclusions
Our studies demonstrate that soluble mediators generated in response to airway epithelial NF‐κB activation orchestrate the breaking of inhalational tolerance and allergic antigen sensitization through the effects of soluble mediators, including IL‐1 and IL‐4, on pulmonary dendritic cells as well as innate lymphoid and CD4+ T cells.
Summary Background Inhalational antigen tolerance typically protects against the development of allergic airway disease but may be overcome to induce allergic sensitization preceding the development ...of asthma. Objectives We examined in vivo whether pre-existing inhalational antigen tolerance could be overcome by activation of the transcription factor NF-kappaB in conducting airway epithelial cells, and used a combination of in vivo and in vitro approaches to examine the mechanisms involved. Methods Wild-type and transgenic mice capable of expressing constitutively active IkappaB kinase beta (CAIKKbeta) in airway epithelium were tolerized to inhaled ovalbumin. Twenty-eight days later, the transgene was transiently expressed and mice were exposed to inhaled OVA on Day 30 in an attempt to overcome inhalational tolerance. Results Following ovalbumin challenge on days 40-42, CAIKKbeta mice in which the transgene had been activated exhibited characteristic features of allergic airway disease, including airway eosinophilia and methacholine hyper-responsiveness. Increases in the CD103+ and CD11bHI lung dendritic cell populations were present in CAIKKbeta mice on Day 31. Bronchoalveolar lavage from mice expressing CAIKKbeta mice induced CD4+ T cells to secrete TH2 and TH17 cytokines, an effect that required IL-4 and IL-1 signalling, respectively. CAIKKbeta mice on Dox demonstrated increased numbers of innate lymphoid type 2 cells (ILC2) in the lung, which also exhibited elevated mRNA expression of the TH2-polarizing cytokine IL-4. Finally, airway epithelial NF-kB activation induced allergic sensitization in CAIKKbeta mice on Dox that required IL-4 and IL-1 signalling in vivo. Conclusions Our studies demonstrate that soluble mediators generated in response to airway epithelial NF-kappaB activation orchestrate the breaking of inhalational tolerance and allergic antigen sensitization through the effects of soluble mediators, including IL-1 and IL-4, on pulmonary dendritic cells as well as innate lymphoid and CD4+ T cells.
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