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BackgroundCarbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms.MethodsTo overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years.ResultsOur CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment.ConclusionsCollectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.

Multidrug resistant organisms are a serious threat to human health.sup.1,2. Fast, accurate antibiotic susceptibility testing (AST) is a critical need in addressing escalating antibiotic resistance, since delays in identifying multidrug resistant organisms increase mortality.sup.3,4 and use of broad-spectrum antibiotics, further selecting for resistant organisms. Yet current growth-based AST assays, such as broth microdilution.sup.5, require several days before informing key clinical decisions. Rapid AST would transform the care of patients with infection while ensuring that our antibiotic arsenal is deployed as efficiently as possible. Growth-based assays are fundamentally constrained in speed by doubling time of the pathogen, and genotypic assays are limited by the ever-growing diversity and complexity of bacterial antibiotic resistance mechanisms. Here we describe a rapid assay for combined genotypic and phenotypic AST through RNA detection, GoPhAST-R, that classifies strains with 94-99% accuracy by coupling machine learning analysis of early antibiotic-induced transcriptional changes with simultaneous detection of key genetic resistance determinants to increase accuracy of resistance detection, facilitate molecular epidemiology and enable early detection of emerging resistance mechanisms. This two-pronged approach provides phenotypic AST 24-36 h faster than standard workflows, with A new assay combining genotypic and phenotypic information accelerates accurate clinical antibiotic susceptibility testing., Author(s): Roby P. Bhattacharyya [sup.1] [sup.2] , Nirmalya Bandyopadhyay [sup.1] , Peijun Ma [sup.1] , Sophie S. Son [sup.1] , Jamin Liu [sup.1] , Lorrie L. He [sup.1] , Lidan [...]

Learning to program is a difficult process for novice programmers. AutoLEP, an automated learning and assessment system, was developed by us, to aid novice programmers to obtain programming skills. AutoLEP is ability-training-oriented. It adopts a novel assessment mechanism, which combines static analysis with dynamic testing to analyze student programs. It not only helps students to sufficiently test the programs, but also evaluates whether the programs meet the specification or not. AutoLEP encourages students to find and work through bugs, by providing automatic syntactic and structural checking, and immediate detailed feedback. This can improve students' learning experience in programming and reduce the workload of the teaching staff. AutoLEP has been used in the C programming course at Harbin Institute of Technology and many other universities since 2004. The feedback on AutoLEP and its incorporation into the introductory programming course has been positive, both by students and teaching staff. (Contains 5 figures and 1 table.)

In this work, we show that the $\beta $ -Ga2O3 Schottky Barrier Diode (SBD) can perform beyond the 1-D unipolar limit of the SiC and GaN by employing a deep trench with filled thick SiO2 layer structure to enhance the breakdown voltage (BV). By doing so, BV and specific on- resistance ($\text{R}_{\text {on},\text {sp}}$) of 5–6 kV and 3.4 $\text{m}\boldsymbol {\Omega } \cdot \text {cm}^{{2}}$ are simultaneously derived on the SBDs with $\beta $ -Ga2O3 epi-layer thickness of 10 $\boldsymbol {\mu } \text{m}$ and diode radius of 90 $\boldsymbol {\mu }\text{m}$. Therefore, the Baliga’s power figure of merit (P-FOM = BV $^{{2}} /\text{R}_{\text {on,sp}}$) is yielded to be 7.4-10.6 GW $/$ cm2. To the best of all authors’ knowledge, those P-FOMs are the highest values among all types of SBDs, which is a significant step towards the Ga2O3 SBD performance improvement. Combined with negligible forward hysteresis and low reverse leakage current, vertical $\beta $ -Ga2O3 SBDs with state-of-the-art BV and P-FOM show its great promise for next generation high voltage and high power applications. [ABSTRACT FROM AUTHOR]

Circadian rhythms are oscillations in biological processes that function as a key adaptation to the daily rhythms of most environments. In the model cyanobacterial circadian clock system, the core oscillator [...]