Does the Presence of Multiple β-Lactamases in Gram-Negative Bacilli Impact the Results of Antimicrobial Susceptibility Tests and Extended-Spectrum β-Lactamase and Carbapenemase Confirmation Methods?

Objectives: Many multidrug-resistant Gram-negative bacilli (MDR-GNB) harbour multiple β-lactamases. The aim of this study was to assess the impact of multiple β-lactamase carriage on the accuracy of susceptibility tests and extended-spectrum β-lactamase (ESBL) and carbapenemase confirmation methods. Methods: A total of 50 MDR-GNB, of which 29 carried multiple β-lactamases, underwent broth microdilution (BMD) and disk diffusion (DD) testing as well as confirmation tests for ESBLs and carbapenemases. Whole-genome sequencing (WGS) was used for β-lactamase gene identification. Results: Categorical agreement of BMD and DD testing results ranged from 86.5 to 97.7% for 10 β-lactam agents. BMD and DD algorithms for ESBL detection were highly variable; 6 of 8 positive strains carried an ESBL plus a carbapenemase or an AmpC enzyme, which may confound antimicrobial selection. The sensitivity and specificity of the modified carbapenem inactivation method (mCIM) were both 100%, whilst mCIM and EDTA-modified carbapenem inactivation method (eCIM) when used together to differentiate serine from metallo-β-lactamase carriage were both 96%. Xpert® Carba-R results (in vitro diagnostic test) were consistent with WGS results. Predicting phenotypic carbapenem resistance from WGS data overall showed 100% specificity but only 66.7% sensitivity for Enterobacterales isolates that were non-susceptible to imipenem and meropenem. Conclusions: Multiple β-lactamases in MDR-GNB does not impact DD results, the utility of mCIM/eCIM tests, or Xpert Carba-R results. However, ESBL algorithms produced inconsistent results and predicting carbapenem resistance from WGS data was problematic in such strains

Does the presence of multiple β-lactamases in Gram-negative bacilli impact the results of antimicrobial susceptibility tests and extended-spectrum β-lactamase and carbapenemase confirmation methods?

Objectives: Many multidrug-resistant Gram-negative bacilli (MDR-GNB) harbour multiple β-lactamases. The aim of this study was to assess the impact of multiple β-lactamase carriage on the accuracy of susceptibility tests and extended-spectrum β-lactamase (ESBL) and carbapenemase confirmation methods. Methods: A total of 50 MDR-GNB, of which 29 carried multiple β-lactamases, underwent broth microdilution (BMD) and disk diffusion (DD) testing as well as confirmation tests for ESBLs and carbapenemases. Whole-genome sequencing (WGS) was used for β-lactamase gene identification. Results: Categorical agreement of BMD and DD testing results ranged from 86.5 to 97.7% for 10 β-lactam agents. BMD and DD algorithms for ESBL detection were highly variable; 6 of 8 positive strains carried an ESBL plus a carbapenemase or an AmpC enzyme, which may confound antimicrobial selection. The sensitivity and specificity of the modified carbapenem inactivation method (mCIM) were both 100%, whilst mCIM and EDTA-modified carbapenem inactivation method (eCIM) when used together to differentiate serine from metallo-β-lactamase carriage were both 96%. Xpert® Carba-R results (in vitro diagnostic test) were consistent with WGS results. Predicting phenotypic carbapenem resistance from WGS data overall showed 100% specificity but only 66.7% sensitivity for Enterobacterales isolates that were non-susceptible to imipenem and meropenem. Conclusions: Multiple β-lactamases in MDR-GNB does not impact DD results, the utility of mCIM/eCIM tests, or Xpert Carba-R results. However, ESBL algorithms produced inconsistent results and predicting carbapenem resistance from WGS data was problematic in such strains

Interacting internal waves explain global patterns of interior ocean mixing

Across the stable density stratification of the abyssal ocean, deep dense water is slowly propelled upward by sustained, though irregular, turbulent mixing. The resulting mean upwelling is key to setting large-scale oceanic circulation properties, such as heat and carbon transport. It is generally accepted that in the ocean interior, this turbulent mixing is caused mainly by breaking internal waves, which are predominantly generated by winds and tides, interact nonlinearly, thereby fluxing energy down to ever smaller scales, and finally become unstable, break and mix the water column. This paradigm forms the conceptual backbone of the widely used Finescale Parameterization. This formula estimates small-scale mixing from the readily observable internal wave activity at larger scales and theoretical scaling laws for the downscale nonlinear energy flux, but has never been fully explained theoretically. Here, we close this gap using wave-wave interaction theory with input from both localized high-resolution experiments and combined global observational datasets. We find near-ubiquitous agreement between our predictions, derived from first-principles alone, and the observed mixing patterns in the global ocean interior. Our findings lay the foundations for a new type of wave-driven mixing parameterization for ocean general circulation models that is entirely physics-based, which is key to reliably represent climate states that differ substantially from today's

A Turnover in the Galaxy Main Sequence of Star Formation at M∗∼1010M⊙M_{*} \sim 10^{10} M_{\odot} for Redshifts z<1.3z < 1.3

The relationship between galaxy star formation rates (SFR) and stellar masses ($M_\ast$) is re-examined using a mass-selected sample of $\sim$62,000 star-forming galaxies at $z \le 1.3$ in the COSMOS 2-deg$^2$ field. Using new far-infrared photometry from $Herschel$-PACS and SPIRE and $Spitzer$-MIPS 24 $\mu$m, along with derived infrared luminosities from the NRK method based on galaxies' locations in the restframe color-color diagram $(NUV - r)$ vs. $(r - K)$, we are able to more accurately determine total SFRs for our complete sample. At all redshifts, the relationship between median $SFR$ and $M_\ast$ follows a power-law at low stellar masses, and flattens to nearly constant SFR at high stellar masses. We describe a new parameterization that provides the best fit to the main sequence and characterizes the low mass power-law slope, turnover mass, and overall scaling. The turnover in the main sequence occurs at a characteristic mass of about $M_{0} \sim 10^{10} M_{\odot}$ at all redshifts. The low mass power-law slope ranges from 0.9-1.3 and the overall scaling rises in SFR as a function of $(1+z)^{4.12 \pm 0.10}$. A broken power-law fit below and above the turnover mass gives relationships of $SFR \propto M_{*}^{0.88 \pm 0.06}$ below the turnover mass and $SFR \propto M_{*}^{0.27 \pm 0.04}$ above the turnover mass. Galaxies more massive than $M_\ast \gtrsim 10^{10}\ M_{\rm \odot}$ have on average, a much lower specific star formation rate (sSFR) than would be expected by simply extrapolating the traditional linear fit to the main sequence found for less massive galaxies.Comment: 16 pages, 7 figures. Accepted for publication in Ap

Recurrent Episodes of Acute Pancreatitis Present to the ED with More Severe Disease by CT than First-Time Acute Pancreatitis

Study Objective: Approximately 30% of patients with one episode of acute pancreatitis experience a recurrent episode. The objective of this study is to compare the severity of the first-time episode versus recurrent episodes of acute pancreatitis based on CT scan. Methods: This study was conducted as part of a retrospective chart review at a single academic urban emergency department from 2012-2016. Criteria for inclusion included clinical symptoms of pancreatitis, age greater than or equal to 18 years, ED diagnosis of acute pancreatitis, and, an abdominal CT scan within 24 hours of triage. Exclusion criteria were traumatic cause of acute pancreatitis and pregnancy. Charts were reviewed by a trained abstractor using structured data collection sheets which included data elements such as a history of acute pancreatitis and the results of an abdominal CT scan. Data abstraction was confirmed for interrater reliability. CT Scans were graded using the Modified CT Severity Index (MCTSI) which grades acute pancreatitis by the presence of inflammation, fluid accumulation, necrosis or extra-pancreatic findings. Results: 283 patients were included in the study. Of these, 110 patients resented with recurrent acute pancreatitis and 173 patients presented with first-time acute pancreatitis. We calculated the mean MCTSI score in both groups and found a significantly higher rate of severity in recurrent acute pancreatitis versus first episode (2.09 vs. 1.43, p\u3c0.05.) Conclusion: Patients with recurrent acute pancreatitis are more likely to present with a more severe episode of acute pancreatitis than patients presenting with first-time acute pancreatitis

Expanding Access to Parasite-based Malaria Diagnosis through Retail Drug shops in Tanzania: Evidence from a Randomized Trial and Implications for Treatment.

Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures. While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal. This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices.\ud Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly. Each district was assigned a different recommended retail price to evaluate the need for a subsidy. Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district. Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing. A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs. RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs. Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8-69.6%) with no difference between intervention districts. Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district. Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing. Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT. Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot. These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy. Trial registration ISRCTN ISRCTN14115509

An ALMA survey of submillimetre galaxies in the COSMOS field: The extent of the radio-emitting region revealed by 3 GHz imaging with the Very Large Array

We determine the radio size distribution of a large sample of 152 SMGs in COSMOS that were detected with ALMA at 1.3 mm. For this purpose, we used the observations taken by the VLA-COSMOS 3 GHz Large Project. One hundred and fifteen of the 152 target SMGs were found to have a 3 GHz counterpart. The median value of the major axis FWHM at 3 GHz is derived to be $4.6\pm0.4$ kpc. The radio sizes show no evolutionary trend with redshift, or difference between different galaxy morphologies. We also derived the spectral indices between 1.4 and 3 GHz, and 3 GHz brightness temperatures for the sources, and the median values were found to be $\alpha=-0.67$ and $T_{\rm B}=12.6\pm2$ K. Three of the target SMGs, which are also detected with the VLBA, show clearly higher brightness temperatures than the typical values. Although the observed radio emission appears to be predominantly powered by star formation and supernova activity, our results provide a strong indication of the presence of an AGN in the VLBA and X-ray-detected SMG AzTEC/C61. The median radio-emitting size we have derived is 1.5-3 times larger than the typical FIR dust-emitting sizes of SMGs, but similar to that of the SMGs' molecular gas component traced through mid-$J$ line emission of CO. The physical conditions of SMGs probably render the diffusion of cosmic-ray electrons inefficient, and hence an unlikely process to lead to the observed extended radio sizes. Instead, our results point towards a scenario where SMGs are driven by galaxy interactions and mergers. Besides triggering vigorous starbursts, galaxy collisions can also pull out the magnetised fluids from the interacting disks, and give rise to a taffy-like synchrotron-emitting bridge. This provides an explanation for the spatially extended radio emission of SMGs, and can also cause a deviation from the well-known IR-radio correlation.Comment: 32 pages (incl. 5 appendices), 17 figures, 7 tables; accepted for publication in A&A; abstract abridged for arXi

The evolution of the cosmic molecular gas density

One of the last missing pieces in the puzzle of galaxy formation and evolution through cosmic history is a detailed picture of the role of the cold gas supply in the star-formation process. Cold gas is the fuel for star formation, and thus regulates the buildup of stellar mass, both through the amount of material present through a galaxy's gas mass fraction, and through the efficiency at which it is converted to stars. Over the last decade, important progress has been made in understanding the relative importance of these two factors along with the role of feedback, and the first measurements of the volume density of cold gas out to redshift 4, (the "cold gas history of the Universe") has been obtained. To match the precision of measurements of the star formation and black-hole accretion histories over the coming decades, a two orders of magnitude improvement in molecular line survey speeds is required compared to what is possible with current facilities. Possible pathways towards such large gains include significant upgrades to current facilities like ALMA by 2030 (and beyond), and eventually the construction of a new generation of radio-to-millimeter wavelength facilities, such as the next generation Very Large Array (ngVLA) concept.Comment: 7 pages, 2 figures, Science White paper submitted to Astro2020 Decadal Surve