Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study

Background: Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA. Methods: CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227. Findings: 1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45–71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20–28) of these patients had died. Interpretation: Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales. Funding: National Institutes of Health

Deep Underground Neutrino Experiment (DUNE), far detector technical design report, volume III: DUNE far detector technical coordination

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module

Roasting and dissolution studies on nonirradiated thorium dioxide/uranium dioxide pellets

Bench scale roasting and dissolution of ThO/sub 2/ and ThO/sub 2//UO/sub 2/ ractor-grade ceramic pellets were studied at the Savannah River Laboratory to define the key parameters affecting dissolution. Pellet breakup, and subsequent dissolution rates, were determined for ThO/sub 2/ and ThO/sub 2//UO/sub 2/ pellets roasted in air or in oxygen. Roasting ThO/sub 2//UO/sub 2/ pellets in air at temperatures from 400 to 900/sup 0/C caused the pellets to crack but not fragment. Roasting whole pellets or fine powdered materials decreased the rate of dissolution in a nitric acid solution containing a fluoride catalyst. Roasting 100% ThO/sub 2/ pellets did not cause cracking or affect the subsequent dissolution rate. Mixed ThO/sub 2//UO/sub 2/ ceramic pellets dissolved at a faster rate than the 100% ThO/sub 2/ pellets. The effect of MgO and CaO on dissolution rate was determined. MgO (approx. 1.0 wt %) increased the dissolution rate of ThO/sub 2/ pellets, an effect which was similar to that obtained by the addition of 20% UO/sub 2/ to the ThO/sub 2/ pellets. The combination of 1% MgO and 20% UO/sub 2/ did not result in an additional increase in dissolution rate. However, the addition of 0.25 to 0.50 wt % CaO did increase the dissolution rate of 80% ThO/sub 2//UO/sub 2/ ceramic pellets. High temperatures (and pressure) were ineffective in dissolving thoria-based fuels in HNO/sub 3/ in the absence of a fluoride catalyst. A process flowsheet outlining the required head end steps for the reprocessing of thoria-based fuels was developed