The supernova rate in local galaxy clusters

We report a measurement of the supernova (SN) rates (Ia and core-collapse) in galaxy clusters based on the 136 SNe of the sample described in Cappellaro et al. (1999) and Mannucci et al. (2005). Early-type cluster galaxies show a type Ia SN rate (0.066 SNuM) similar to that obtained by Sharon et al. (2007) and more than 3 times larger than that in field early-type galaxies (0.019 SNuM). This difference has a 98% statistical confidence level. We examine many possible observational biases which could affect the rate determination, and conclude that none of them is likely to significantly alter the results. We investigate how the rate is related to several properties of the parent galaxies, and find that cluster membership, morphology and radio power all affect the SN rate, while galaxy mass has no measurable effect. The increased rate may be due to galaxy interactions in clusters, inducing either the formation of young stars or a different evolution of the progenitor binary systems. We present the first measurement of the core-collapse SN rate in cluster late-type galaxies, which turns out to be comparable to the rate in field galaxies. This suggests that no large systematic difference in the initial mass function exists between the two environments.Comment: MNRAS, revised version after referee's comment

Immunosuppression and outcomes in adult patients with de novo acute myeloid leukemia with normal karyotypes

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; \u3e5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic studies, we characterized 28 normal karyotype (NK)-AML patients with \u3e5 y first remissions after chemotherapy (LFRs) and compared them to a well-matched group of 31 NK-AML patients who relapsed within 2 y (standard first remissions [SFRs]). Our combined analyses indicated that genetic-risk profiling at presentation (as defined by European LeukemiaNet [ELN] 2017 criteria) was not sufficient to explain the outcomes of many SFR cases. Single-cell RNA-sequencing studies of 15 AML samples showed that SFR AML cells differentially expressed many genes associated with immune suppression. The bone marrow of SFR cases had significantly fewer CD

The Extended [C ii] under Construction? Observation of the Brightest High-z Lensed Star-forming Galaxy at z = 6.2

We present results of [C ii] 158 μm emission line observations, and report the spectroscopic redshift confirmation of a strongly lensed (μ ∼ 20) star-forming galaxy, MACS0308-zD1 at z = 6.2078 ± 0.0002. The [C ii] emission line is detected with a signal-to-noise ratio >6 within the rest-frame UV-bright clump of the lensed galaxy (zD1.1) and exhibits multiple velocity components; the narrow [C ii] has a velocity full width half maximum (FWHM) of 110 ± 20 km s−1, while broader [C ii] is seen with an FWHM of 230 ± 50 km s−1. The broader [C ii] component is blueshifted (−80 ± 20 km s−1) with respect to the narrow [C ii] component, and has a morphology that extends beyond the UV-bright clump. We find that, while the narrow [C ii] emission is most likely associated with zD1.1, the broader component is possibly associated with a physically distinct gas component from zD1.1 (e.g., outflowing or inflowing gas). Based on the nondetection of λ158μm dust continuum, we find that MACS0308-zD1's star formation activity occurs in a dust-free environment indicated by a strong upper limit of infrared luminosity ≲9 × 108L⊙. Targeting this strongly lensed faint galaxy for follow-up Atacama Large Millimeter/submillimeter Array and JWST observations will be crucial to characterize the details of typical galaxy growth in the early Universe

High-Redshift Galaxy Candidates at z=9−13z = 9-13 as Revealed by JWST Observations of WHL0137-08

JWST was designed to peer into the distant universe and study galaxies nearer the beginning of time than previously. Here we report the discovery of 12 galaxy candidates observed 300-600 Myr after the Big Bang with photometric redshifts between z ~ 8.5-13 measured using JWST NIRCam imaging of the galaxy cluster WHL0137 observed in 8 filters spanning 0.8-5.0 $\mu$m, plus 9 HST filters spanning 0.4-1.7 $\mu$m. Three of these candidates are gravitationally lensed by the foreground galaxy cluster and have magnifications of $\mu \sim 3 - 8$. The remaining nine candidates are located in a second JWST NIRCam module, centered ~29' from the cluster center, with expected magnifications of $\mu$ <~ 1.1. Our sample of high-redshift candidates have observed F200W AB magnitudes between 25.9 and 28.1 mag and intrinsic F200W AB magnitudes between 26.4 and 29.7 mag ($M_{UV}$ = -22.5 to -17). We find the stellar masses of these galaxies are in the range $\log M_{*}/M_{\odot}$ = 8 - 9, and down to 7.5 for the lensed galaxies. All are young with mass-weighted ages < 100 Myr, low dust content $A_V$ < 0.15 mag, and high specific star formation rates sSFR ~10-50 Gyr$^{-1}$ for most. One z ~ 9 candidate is consistent with an age < 5 Myr and a sSFR ~250 Gyr$^{-1}$, as inferred from a strong F444W excess, implying [OIII]+H-beta rest-frame equivalent width ~2000 Angstrom, although an older and redder z~ 10 object is also allowed. Another z~9 candidate ID9356 is lensed into an arc 2.6" long by the effects of strong gravitational lensing ($\mu$~8), and has at least two bright knots of unevenly distributed star formation. This arc is the most spatially-resolved galaxy at z~9 known to date, revealing structures ~30 pc across. Follow-up spectroscopy of WHL0137 with JWST/NIRSpec is planned for later this year, which will validate some of these candidates and study their physical properties in more detail.Comment: submitted to Ap

A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol

Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented. Objective: Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults. Design: Observational prospective cohort study. Setting: Six Canadian oncology centers (3 pediatric, 1 adult and 2 both). Patients: Three hundred adults and 300 children planned to receive cisplatin therapy. Measurements: During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort. Methods: Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival. Limitations: It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge. Conclusions: ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices

The Origin and Evolution of Mutations in Acute Myeloid Leukemia

SummaryMost mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is “captured” as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse

The Profanation of Revelation: On Language and Immanence in the Work of Giorgio Agamben

This essay seeks to articulate the many implications which Giorgio Agamben’s work holds for theology. It aims therefore to examine his (re)conceptualizations of language, in light of particular historical glosses on the ‘name of God’ and the nature of the ‘mystical’, as well as to highlight the political task of profanation, one of his most central concepts, in relation to the logos said to embody humanity’s ‘religious’ quest to find its Voice. As such, we see how he challenges those standard (ontotheological) notions of transcendence which have been consistently aligned with various historical forms of sovereignty. In addition, I intend to present his redefinition of revelation as solely the unveiling of the ‘name of God’ as the fact of our linguistic being, a movement from the transcendent divine realm to the merely human world before us. By proceeding in this manner, this essay tries to close in on one of the largest theological implications contained within Agamben’s work: the establishment of an ontology that could only be described as a form of ‘absolute’ immanence, an espousal of some form of pantheism (or perhaps panentheism) yet to be more fully pronounced within his writings

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy