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The speed-accuracy trade-off (SAT) suggests that time constraints reduce response accuracy. Its relevance in observational settings--where response time (RT) may not be constrained but respondent speed may still vary--is unclear. Using 29 data sets containing data from cognitive tasks, we use a flexible method for identification of the SAT (which we test in extensive simulation studies) to probe whether the SAT holds. We find inconsistent relationships between time and accuracy; marginal increases in time use for an individual do not necessarily predict increases in accuracy. Additionally, the speed-accuracy relationship may depend on the underlying difficulty of the interaction. We also consider the analysis of items and individuals; of particular interest is the observation that respondents who exhibit more within-person variation in response speed are typically of lower ability. We further find that RT is typically a weak predictor of response accuracy. Our findings document a range of empirical phenomena that should inform future modeling of RTs collected in observational settings. [This work was co-written by the Project iLEAD Consortium.]

Based on concerns about the item response theory (IRT) linking approach used in the Programme for International Student Assessment (PISA) until 2012 as well as the desire to include new, more complex, interactive items with the introduction of computer-based assessments, alternative IRT linking methods were implemented in the 2015 PISA round. The new linking method represents a concurrent calibration using all available data, enabling us to find item parameters that maximize fit across all groups and allowing us to investigate measurement invariance across groups. Apart from the Rasch model that historically has been used in PISA operational analyses, we compared our method against more general IRT models that can incorporate item-by-country interactions. The results suggest that our proposed method holds promise not only to provide a strong linkage across countries and cycles but also to serve as a tool for investigating measurement invariance.

UnlabelledThe AcrB protein of Escherichia coli, together with TolC and AcrA, forms a contiguous envelope conduit for the capture and extrusion of diverse antibiotics and cellular metabolites. In this study, we sought to expand our knowledge of AcrB by conducting genetic and functional analyses. We began with an AcrB mutant bearing an F610A substitution in the drug binding pocket and obtained second-site substitutions that overcame the antibiotic hypersusceptibility phenotype conferred by the F610A mutation. Five of the seven unique single amino acid substitutions--Y49S, V127A, V127G, D153E, and G288C--mapped in the periplasmic porter domain of AcrB, with the D153E and G288C mutations mapping near and at the distal drug binding pocket, respectively. The other two substitutions--F453C and L486W--were mapped to transmembrane (TM) helices 5 and 6, respectively. The nitrocefin efflux kinetics data suggested that all periplasmic suppressors significantly restored nitrocefin binding affinity impaired by the F610A mutation. Surprisingly, despite increasing MICs of tested antibiotics and the efflux of N-phenyl-1-naphthylamine, the TM suppressors did not improve the nitrocefin efflux kinetics. These data suggest that the periplasmic substitutions act by influencing drug binding affinities for the distal binding pocket, whereas the TM substitutions may indirectly affect the conformational dynamics of the drug binding domain.ImportanceThe AcrB protein and its homologues confer multidrug resistance in many important human bacterial pathogens. A greater understanding of how these efflux pump proteins function will lead to the development of effective inhibitors against them. The research presented in this paper investigates drug binding pocket mutants of AcrB through the isolation and characterization of intragenic suppressor mutations that overcome the drug susceptibility phenotype of mutations affecting the drug binding pocket. The data reveal a remarkable structure-function plasticity of the AcrB protein pertaining to its drug efflux activity.

The original article can be found online at https://doi.org/10.1038/s41598-022-12376-1. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-12376-1, published online 17 May 2022 The original version of this Article contained an error in the spelling of the author Dinesh Nath which was incorrectly given as Dinesh Nash. [Extracted from the article]

In Gram-negative bacteria, multidrug efflux transporters function in complexes with periplasmic membrane fusion proteins ( MFPs) that enable antibiotic efflux across the outer membrane. In this study, we analyzed the function, composition and assembly of the triclosan efflux transporter TriABC- OpmH from P seudomonas aeruginosa. We report that this transporter possesses a surprising substrate specificity that encompasses not only triclosan but the detergent SDS, which are often used together in antibacterial soaps. These two compounds interact antagonistically in a TriABC-dependent manner and negate antibacterial properties of each other. Unlike other efflux pumps that rely on a single MFP for their activities, two different MFPs, TriA and TriB, are required for triclosan/ SDS resistance mediated by TriABC- OpmH. We found that analogous mutations in the α-helical hairpin and membrane proximal domains of TriA and TriB differentially affect triclosan efflux and assembly of the complex. Furthermore, our results show that TriA and TriB function as a dimer, in which TriA is primarily responsible for stabilizing interactions with the outer membrane channel, whereas TriB is important for the stimulation of the transporter. We conclude that MFPs are engaged into complexes as asymmetric dimers, in which each protomer plays a specific role. [ABSTRACT FROM AUTHOR]

The tripartite AcrAB- TolC multidrug efflux pump of E scherichia coli is the central conduit for cell-toxic compounds and contributes to antibiotic resistance. While high-resolution structures of all three proteins have been solved, much remains to be learned as to how the individual components come together to form a functional complex. In this study, we investigated the importance of the AcrB β-hairpins belonging to the DN and DC subdomains, which are presumed to dock with TolC, in complex stability and activity of the complete pump. Our data show that the DN subdomain β-hairpin residues play a more critical role in complex stability and activity than the DC subdomain hairpin residues. The failure of the AcrB DN β-hairpin deletion mutant to engage with TolC leads to the drug hypersensitivity phenotype, which is reversed by compensatory alterations in the lipoyl and β-barrel domains of AcrA. Moreover, AcrA and TolC mutants that induce TolC opening also reverse the drug hypersensitivity phenotype of the AcrB β-hairpin mutants, indicating a failure by the AcrB mutant to interact and thus induce TolC opening on its own. Together, these data suggest that both AcrB β-hairpins and AcrA act to stabilize the tripartite complex and induce TolC opening for drug expulsion. [ABSTRACT FROM AUTHOR]

Introduction. Simethicone is an over-the-counter product that is frequently used by clinicians during endoscopic procedures to reduce foaming and improve visualization. Published studies have found simethicone residue on endoscopes after cleaning and disinfecting the devices as per the manufacturer's instructions. Some literature suggests that simethicone residue may reduce disinfection efficacy and increase the risk of patient infections. Gap Statement. However, there appears to be a lack of direct evidence in the literature to either disprove this or correlate simethicone presence with an increased microbial risk. Aim : Research was conducted to evaluate the in vitro impact of simethicone on disinfection efficacy. Methodology. Bacteria were grown in a microtitre plate assay in the presence of a range of simethicone concentrations and then treated with a disinfectant. Bacterial growth was assessed by spotting each microtitre well onto an agar plate. Results. The results demonstrated that, under the conditions tested, simethicone did not reduce the efficacy of Cidex ortho-phthalaldehyde disinfectant, which demonstrated at least a 6-log unit reduction in bacterial viability. Additional experiments showed that direct exposure to 66 mg ml -1 of simethicone reduced bacterial viability. Conclusion. These results indicate that simethicone may not reduce the bactericidal efficacy of disinfectant during reprocessing, under certain conditions.