Feedback from Central Black Holes in Elliptical Galaxies: Two-dimensional Models Compared to One-dimensional Models

We extend the black hole (BH) feedback models of Ciotti, Ostriker, and Proga to two dimensions. In this paper, we focus on identifying the differences between the one-dimensional and two-dimensional hydrodynamical simulations. We examine a normal, isolated $L_*$ galaxy subject to the cooling flow instability of gas in the inner regions. Allowance is made for subsequent star formation, Type Ia and Type II supernovae, radiation pressure, and inflow to the central BH from mildly rotating galactic gas which is being replenished as a normal consequence of stellar evolution. The central BH accretes some of the infalling gas and expels a conical wind with mass, momentum, and energy flux derived from both observational and theoretical studies. The galaxy is assumed to have low specific angular momentum in analogy with the existing one-dimensional case in order to isolate the effect of dimensionality. The code then tracks the interaction of the outflowing radiation and winds with the galactic gas and their effects on regulating the accretion. After matching physical modeling to the extent possible between the one-dimensional and two-dimensional treatments, we find essentially similar results in terms of BH growth and duty cycle (fraction of the time above a given fraction of the Eddington luminosity). In the two-dimensional calculations, the cool shells forming at 0.1--1 kpc from the center are Rayleigh--Taylor unstable to fragmentation, leading to a somewhat higher accretion rate, less effective feedback, and a more irregular pattern of bursting compared to the one-dimensional case.Comment: 15 pages, 10 figures, ApJ 237:26. Updated to match published versio

Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.ISF and SOR were supported by the Wellcome Trust, the MRC Centre for Obesity and Related Disorders and the UK NIHR Cambridge Biomedical Research Centre.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S1096719213001145#

Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial.

BACKGROUND: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock. METHODS AND DESIGN: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018

Feedback from central black holes in elliptical galaxies. II: Can purely mechanical energy feedback models work?

By using high-resolution 1D hydrodynamical simulations, we investigate the effects of purely mechanical feedback from super massive black holes (SMBHs) in the evolution of elliptical galaxies for a broad range of feedback efficiencies and compare the results to four major observational constraints. In particular, we focus on 1) the central black hole to stellar mass ratio of the host galaxy, 2) the lifetime of the luminous quasar phase, 3) the mass of stars formed in the host galaxy within the last Gyr, and 4) the X-ray luminosity of the hot diffuse gas. As a result, we try to pin down the most successful range of mechanical feedback efficiencies. We find that while low feedback efficiencies result in too much growth of the SMBH, high efficiencies totally blow out the hot interstellar gas, and the models are characterized by very low thermal X-ray luminosity well below the observed range. The net lifetime of the quasar phase is strongly coupled to the mass ratio between SMBH and its host galaxy, while the X-ray luminosity is generally correlated to the recent star formation within the last Gyr. When considering the popularly adopted model of the constant feedback efficiency, the feedback energy deposited into the ambient medium should be more than 0.01% of the SMBH accretion energy to be consistent with the SMBH mass to stellar mass ratio in the local universe. Yet, the X-ray luminosity of the hot gas favors about 0.005% of the accretion energy as the mechanical AGN feedback energy. We conclude that the purely mechanical feedback mode is unlikely to be simultaneously compatible with all four observable tests, even allowing a broad range of feedback efficiencies, and that including both radiative and mechanical feedback together may be a solution to comply the observational constraints. [abridged]Comment: Accepted to Ap

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Splenic pseudoaneurysm in a child with hereditary pancreatitis

Splenic artery pseudoaneurysm (SAP) formation is an uncommon complication of pancreatitis. It is believed to be the result of vascular erosion by pancreatic enzymes, a process that compromises the integrity of the splenic artery wall. The final result is a weak, expanded vessel wall that may hemorrhage into the peritoneal cavity or retroperitoneal space. There are no known reports of SAP in the pediatric population or in patients with hereditary pancreatitis. We report a case of SAP formation in a 5-year-old child with hereditary pancreatitis that was successfully managed via transcatheter coil embolization of the splenic artery