Accessory Genomes Drive Independent Spread of Carbapenem- Resistant Klebsiella pneumoniae Clonal Groups 258 and 307 in Houston, TX

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is an urgent public health threat. Worldwide dissemination of CRKp has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CRKp CG307 lineage. Houston, TX, is the first large city in the United States with detected cocirculation of both CRKp CG307 and CG258. We sought to characterize the genomic and clinical factors contributing to the parallel endemic spread of CG258 and CG307. CRKp isolates were collected as part of the prospective, Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacterales 2 (CRACKLE-2) study. Hybrid short-read and long-read genome assemblies were generated from 119 CRKp isolates (95 originated from Houston hospitals). A comprehensive characterization of phylogenies, gene transfer, and plasmid content with pan-genome analysis was performed on all CRKp isolates. Plasmid mating experiments were performed with CG307 and CG258 isolates of interest. Dissection of the accessory genomes suggested independent evolution and limited horizontal gene transfer between CG307 and CG258 lineages. CG307 contained a diverse repertoire of mobile genetic elements, which were shared with other non-CG258 K. pneumoniae isolates. Three unique clades of Houston CG307 isolates clustered distinctly from other global CG307 isolates, indicating potential selective adaptation of particular CG307 lineages to their respective geographical niches. CG307 strains were often isolated from the urine of hospitalized patients, likely serving as important reservoirs for genes encoding carbapenemases and extendedspectrum b-lactamases. Our findings suggest parallel cocirculation of high-risk lineages with potentially divergent evolution

Axial power monitoring uncertainty in the Savannah River Reactors

The results of this analysis quantified the uncertainty associated with monitoring the Axial Power Shape (APS) in the Savannah River Reactors. Thermocouples at each assembly flow exit map the radial power distribution and are the primary means of monitoring power in these reactors. The remaining uncertainty in power monitoring is associated with the relative axial power distribution. The APS is monitored by seven sensors that respond to power on each of nine vertical Axial Power Monitor (APM) rods. Computation of the APS uncertainty, for the reactor power limits analysis, started with a large database of APM rod measurements spanning several years of reactor operation. A computer algorithm was used to randomly select a sample of APSs which were input to a code. This code modeled the thermal-hydraulic performance of a single fuel assembly during a design basis Loss-of Coolant Accident. The assembly power limit at Onset of Significant Voiding was computed for each APS. The output was a distribution of expected assembly power limits that was adjusted to account for the biases caused by instrumentation error and by measuring 7 points rather than a continuous APS. Statistical analysis of the final assembly power limit distribution showed that reducing reactor power by approximately 3% was sufficient to account for APS variation. This data confirmed expectations that the assembly exit thermocouples provide all information needed for monitoring core power. The computational analysis results also quantified the contribution to power limits of the various uncertainties such as instrumentation error

Axial power monitoring uncertainty in the Savannah River Reactors

The results of this analysis quantified the uncertainty associated with monitoring the Axial Power Shape (APS) in the Savannah River Reactors. Thermocouples at each assembly flow exit map the radial power distribution and are the primary means of monitoring power in these reactors. The remaining uncertainty in power monitoring is associated with the relative axial power distribution. The APS is monitored by seven sensors that respond to power on each of nine vertical Axial Power Monitor (APM) rods. Computation of the APS uncertainty, for the reactor power limits analysis, started with a large database of APM rod measurements spanning several years of reactor operation. A computer algorithm was used to randomly select a sample of APSs which were input to a code. This code modeled the thermal-hydraulic performance of a single fuel assembly during a design basis Loss-of Coolant Accident. The assembly power limit at Onset of Significant Voiding was computed for each APS. The output was a distribution of expected assembly power limits that was adjusted to account for the biases caused by instrumentation error and by measuring 7 points rather than a continuous APS. Statistical analysis of the final assembly power limit distribution showed that reducing reactor power by approximately 3% was sufficient to account for APS variation. This data confirmed expectations that the assembly exit thermocouples provide all information needed for monitoring core power. The computational analysis results also quantified the contribution to power limits of the various uncertainties such as instrumentation error

A multicentre stewardship initiative to decrease excessive duration of antibiotic therapy for the treatment of community-acquired pneumonia

The increased emphasis on pneumonia-related performance measures and patient outcomes has led hospitals to implement multifaceted approaches to quickly identify patients with community-acquired pneumonia (CAP), start timely therapy and reduce readmission. However, there has been minimal focus on duration of therapy (DOT) and patients often receive prolonged antibiotic courses. The IDSA and American Thoracic Society (IDSA/ATS) CAP guidelines recommend 5 days of therapy for clinically stable patients that quickly defervesce and stewardship teams are well positioned to influence prescribing practices.Determine the impact of a prospective stewardship intervention on total antibiotic DOT and associated clinical outcomes in hospitalized patients with CAP.This multicentre, quasi-experimental study evaluated three concurrent interventions over a 6 month period to promote appropriate DOT. All centres updated institutional CAP guidelines to promote IDSA/ATS-concordant DOT, provided education and conducted daily audit and feedback with intervention to provide patient-specific DOT recommendations.A total of 600 patients with CAP were included (307 in the historical control group and 293 in the stewardship intervention group). The stewardship intervention increased compliance with DOT recommendations (42% versus 5.6%, P

Axial power monitor rod issues and resolution for K-14.1

A recent concern arose over the treatment of uncertainty associated with the K-Reactor axial power monitors (APMs). There are nine axial power monitor rods located at various positions in the K-Reactor core. By comparing the output of one sensor near the top of the rod to the output of another sensor near the bottom of the rod, the relative ratio of the neutron flux from the top to the bottom of the core can be determined. This ratio is called the roof-top-ratio (RTR) and is the output of a top sensor (Sensor 2) divided by the output of a bottom sensor (Sensor 6). The RTR is important to the safety analyses because when the RTR is maintained within certain ranges, the severity of reactivity transients is limited. There are uncertainties associated with the equipment`s ability to measure the true roof top ratio. It was determined recently that sufficient uncertainty was not accounted for either in reactor operation or in the safety analyses. The concern about uncertainty was addressed for three separate issues. One issue dear with the linear response of the sensors for power ranges planned for K-Reactor operation. The second issue dear with overall uncertainty in the RTR channel. The third issue dear with apparent large ranges in confidence bands for the RTR at low reactor powers as represented by original vendor data. Plots of sparse vendor data indicated unacceptably large uncertainties in RTR would have to be accounted for at the power ranges planned for K-Reactor operation. These concerns were brought to management`s attention through the existing procedures for notification, irrespective of their potential impact on the restart schedule. Analyses have been completed to resolve the APM issues described above, and work is progressing to take the needed steps to change operational procedures