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Green, D. A.

Publications and source records attributed to Green, D. A..

4 recordsLinked to original sources

Comparative Evaluation of Commercial Gradient Diffusion and Disk Diffusion Tests for Aztreonam-Avibactam Susceptibility Testing

BackgroundAztreonam-avibactam (AZA) is a recently approved agent active against metallo-{beta}-lactamase-producing Enterobacterales. However, independent evaluations of commercially available antimicrobial susceptibility testing (AST) products remain limited. MethodsWe evaluated 56 carbapenem-resistant Enterobacterales isolates using four newly available AZA AST products, including two gradient diffusion (bioMerieux Etest; Liofilchem MIC Test Strip) and two disk diffusion (Hardy, Liofilchem) tests across three Mueller-Hinton agar manufacturers at two independent clinical laboratories. A diverse isolate collection enriched for nonsusceptible and breakpoint-adjacent MICs was used to rigorously assess categorical agreement. Broth microdilution (BMD) was used as the reference method. Essential agreement (EA), categorical agreement (CA), error rates, and reproducibility were analyzed. ResultsAll four commercial AST products demonstrated acceptable analytical performance compared with reference BMD. Gradient diffusion demonstrated high EA (bioMerieux 94.3%, Liofilchem 90.5%), whereas CA ranged from 83.3% to 89.0% across all four products. Minor errors accounted for all categorical discrepancies, and occurred almost exclusively among breakpoint-adjacent isolates. Media-related variability was modest, and quality control performance was generally high, with strong within-site precision and consistent performance across laboratories. ConclusionsThis study provides the first comprehensive head-to-head comparison of commercial AZA susceptibility testing products and supports their implementation in clinical microbiology laboratories.

microbiology↗

Walking on the Moon: Hypogravity drives the emergence of a proprioception-dependent locomotor state

Animals must adapt locomotion to changing environmental conditions, but how the nervous system flexibly controls movement remains unclear. Gravity provides a powerful perturbation because it alters body loading, limb dynamics, and proprioceptive feedback. Apollo astronauts often skipped on the Moon, adopting an asymmetric gait rarely used on Earth, yet the sensorimotor basis of this behaviour is unknown. Here, by studying hypogravity locomotion in humans and mice, we show that reduced gravity reveals a conserved proprioception-dependent mechanism for locomotor state expression. In humans, skipping in simulated lunar gravity is generated through flexible temporal reconfiguration of existing motor modules rather than construction of a new motor architecture. In mice, simulated lunar gravity elicited a skipping-like locomotor state, and genetic elimination of muscle proprioceptors abolished this response. Thus, hypogravity reveals how proprioceptive feedback enables flexible expression of locomotor states.

neuroscience↗

Challenges in establishing epidemiological cut-off values for the Burkholderia cepacia complex

The Burkholderia cepacia complex (BCC) is comprised of 24 species of Gram-negative bacteria that cause opportunistic infections. While antimicrobial susceptibility testing (AST) has historically been used to guide treatment for BCC infections, recent work highlighting problems with AST for these organisms led the Clinical and Laboratory Sciences Institute (CLSI) to remove disk diffusion (DD) and minimal inhibitory concentration (MIC) breakpoints for BCC from its M100 standards document. Epidemiological cut-off values (ECVs) may be helpful to clinicians in the absence of breakpoints, as they may be used to determine whether an isolate has a wild-type or non-wild-type phenotype. Here we present an analysis of BCC ECVs for ceftazidime (CAZ), levofloxacin (LVX), meropenem (MEM), minocycline (MIN), and trimethoprim-sulfamethoxazole (TMP-SMX). ECVs were calculated using MIC data from 3 previous studies and 3 independent laboratories for 1,896 BCC isolates. ECVs were 16 g/ml for CAZ, 8 g/ml for LVX, 16 g/ml for MEM, and 8 g/ml for MIN. The ECV for TMP-SMX varied depending on the analysis from 2 g/ml, 8 g/ml, and 16 g/ml and therefore could not be reliably established. Challenges with establishing ECVs for BCC include limitations with the pooled MIC dataset, broad MIC distributions, and high ECVs that are above the obsolete susceptible MIC breakpoints. These challenges limit the clinical utility of ECVs for these organisms and supported removal of ECVs from the CLSI M100 standards document. IMPORTANCEThe Burkholderia cepacia complex is a group of bacterial species that cause difficult-to-treat opportunistic infections. Recently, clinical breakpoints, which are used to determine whether organisms are susceptible to certain antimicrobials, were removed from Clinical and Laboratory Standards Institute (CLSI) standards for these organisms due to problems with antimicrobial susceptibility testing performance. Clinicians are now faced with the challenge of how to treat these complex infections without clinical breakpoints. Here we determine epidemiological cut-off values (ECVs) for relevant antimicrobials for the B. cepacia complex. While we established ECVs for four antimicrobials, we encountered significant challenges in our analyses, including limitations with data for these organisms and high ECVs that are not clinically useful. These challenges limit the practical use of these ECVs in helping guide clinicians on treatment and supported the eventual removal of ECVs from the CLSI M100 standards document.

microbiology↗

Seasonal plasticity in morphology and metabolism differs between migratory North American and resident Costa Rican monarch butterflies

Environmental heterogeneity in temperate latitudes is expected to maintain seasonally plastic life-history strategies that include the tuning of morphologies and metabolism that support overwintering. For species that have expanded their ranges into tropical latitudes, it is unclear the extent to which the capacity for plasticity will be maintained or will erode with disuse. The migratory generations of the North American (NA) monarch butterfly Danaus plexippus lead distinctly different lives from their summer generation NA parents and their tropical descendants living in Costa Rica (CR). NA migratory monarchs postpone reproduction, travel thousands of kilometers south to overwinter in Mexico, and subsist on little food for months. Whether recently dispersed populations of monarchs such as those in Costa Rica, which are no longer subject to selection imposed by migration, retain ancestral seasonal plasticity is unclear. To investigate differences in seasonal plasticity, we reared NA and CR monarchs in summer and autumn in Illinois, USA, and measured seasonal reaction norms for aspects of morphology and metabolism related to flight. NA monarchs were seasonally plastic in forewing and thorax size, increasing wing area and thorax to body mass ratio in autumn. While CR monarchs increased thorax mass in autumn, they did not increase the area of the forewing. NA monarchs maintained similar resting and maximal flight metabolic rates across seasons. However, CR monarchs had elevated metabolic rates in autumn. Our findings suggest that the recent expansion of monarchs into habitats that support year-round breeding may be accompanied by (1) the loss of some aspects of morphological plasticity as well as (2) the underlying physiological mechanisms that maintain metabolic homeostasis in the face of temperature heterogeneity.

evolutionary biology↗