Three is the magic number -- distance measurement of NGC 3147 using SN 2021hpr and its siblings

The nearby spiral galaxy NGC 3147 hosted three Type Ia supernovae (SNe Ia) in the past decades, which have been subjects of intense follow-up observations. Simultaneous analysis of their data provides a unique opportunity for testing the different light curve fitting methods and distance estimations. The detailed optical follow-up of SN 2021hpr allows us to revise the previous distance estimations to NGC 3147, and compare the widely used light curve fitting algorithms to each other. After the combination of the available and newly published data of SN 2021hpr, its physical properties can be also estimated with higher accuracy. We present and analyse new BVgriz and Swift photometry of SN 2021hpr to constrain its general physical properties. Together with its siblings, SNe 1997bq and 2008fv, we cross-compare the individual distance estimates of these three SNe given by the SALT code, and also check their consistency with the results from the MLCS2k2 method. The early spectral series of SN 2021hpr are also fit with the radiative spectral code TARDIS in order to verify the explosion properties and constrain the chemical distribution of the outer ejecta. After combining the distance estimates for the three SNe, the mean distance to their host galaxy, NGC 3127, is 42.5 $\pm$ 1.0 Mpc, which matches with the distance inferred by the most up-to-date LC fitters, SALT3 and BayeSN. We confirm that SN~2021hpr is a Branch-normal Type Ia SN that ejected $\sim 1.12 \pm 0.28$ M$_\odot$ from its progenitor white dwarf, and synthesized $\sim 0.44 \pm 0.14$ M$_\odot$ of radioactive $^{56}$Ni.Comment: 16 pages, 17 figures, 11 tables; accepted for publication in A&

Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells

Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte–MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Triple-differential cross sections for the ionization of NH

Triple differential cross sections are calculated for the ionization of NH3 by positron impact in coplanar and perpendicular geometrical arrangements. The cross sections are determined for symmetrically emerging particles with equal energies. The positron cross sections are compared with previously calculated electron cross sections for the same kinematical conditions

Ionization of NH

Calculated triple differential cross sections are presented for the ionization of NH3 and CH4 molecules by electron impact. The cross sections are determined for symmetrical coplanar and perpendicular geometrical arrangements. The obtained results reproduce in most cases the main features observed in the experimental data for both geometries

Triple differential cross sections for the ionization of water by electron impact

Calculated triple differential cross sections are presented for the ionization of the 3a1 orbital of water by electron impact. The cross sections are determined for symmetric coplanar and non-coplanar geometrical arrangements. The obtained results show reasonable agreement with experimental data for both geometries

Pair function at coincidence and ground-state energy for interacting systems of two fermions with isotropic harmonic confinement and antiparallel spins

Harmonically confined isotropic two-dimensional fermion systems with different interparticle interactions are compared and contrasted. For a harmonic oscillator interparticle force, the pair correlation function n2(r,r′) at coincidence is determined analytically and is shown to uniquely fix the ground-state energy. The two-electron Hookean atom is cited for comparison. © 2001 Elsevier Science B.V. All rights reserved.This work is also supported by the Concerted Action Programme of the University of Antwerp. A.R.'s work was supported by European Union RTN project NANOPHASE (HPRN-CT-2000-00167), Basque Country University, Basque Hezkuntza Saila, Iberdola S.A. and DGES. I.N. was supported by the OTKA (grant no. T034363).Peer Reviewe