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ABSTRACT Severe COVID-19 has been associated with coinfections with bacterial and fungal pathogens. Notably, patients with COVID-19 who develop Staphylococcus aureus bacteremia exhibit higher rates of mortality than those infected with either pathogen alone. To understand this clinical scenario, we collected and examined S. aureus blood and respiratory isolates from a hospital in New York City during the early phase of the pandemic from both SARS-CoV-2+ and SARS-CoV-2− patients. Whole genome sequencing of these S. aureus isolates revealed broad phylogenetic diversity in both patient groups, suggesting that SARS-CoV-2 coinfection was not associated with a particular S. aureus lineage. Phenotypic characterization of the contemporary collection of S. aureus isolates from SARS-CoV-2+ and SARS-CoV-2− patients revealed no notable differences in several virulence traits examined. However, we noted a trend toward overrepresentation of S. aureus bloodstream strains with low cytotoxicity in the SARS-CoV-2+ group. We observed that patients coinfected with SARS-CoV-2 and S. aureus were more likely to die during the acute phase of infection when the coinfecting S. aureus strain exhibited high or low cytotoxicity. To further investigate the relationship between SARS-CoV-2 and S. aureus infections, we developed a murine coinfection model. These studies revealed that infection with SARS-CoV-2 renders mice susceptible to subsequent superinfection with low cytotoxicity S. aureus. Thus, SARS-CoV-2 infection sensitizes the host to coinfections, including S. aureus isolates with low intrinsic virulence.IMPORTANCEThe COVID-19 pandemic has had an enormous impact on healthcare across the globe. Patients who were severely infected with SARS-CoV-2, the virus causing COVID-19, sometimes became infected with other pathogens, which is termed coinfection. If the coinfecting pathogen is the bacterium Staphylococcus aureus, there is an increased risk of patient death. We collected S. aureus strains that coinfected patients with SARS-CoV-2 to study the disease outcome caused by the interaction of these two important pathogens. We found that both in patients and in mice, coinfection with an S. aureus strain lacking toxicity resulted in more severe disease during the early phase of infection, compared with infection with either pathogen alone. Thus, SARS-CoV-2 infection can directly increase the severity of S. aureus infection.

Abstract Background Atrio-esophageal fistula formation following radiofrequency ablation of left atrial tachyarrhythmias is a rare but devastating complication. Esophageal injuries are believed to be precursors of fistula formation and reported to occur in up to 47% of patients. This study investigates the incidence of esophageal lesions when real time esophageal temperature monitoring and temperature limitation is used. Methods 184 consecutive patients underwent open irrigated radiofrequency ablation of left atrial tachyarrhythmias. An esophageal temperature probe consisting of three independent thermocouples was used for temperature monitoring. A temperature limit of 40°C was defined to interrupt energy delivery. All patients underwent esophageal endoscopy the next day. Results Endoscopy revealed ulcer formation in 3/184 patients (1.6%). No patient developed atrio-esophageal fistula. Patient and disease characteristics had no influence on ulcer formation. The temperature threshold of 40°C was reached in 157/184 patients. A temperature overshoot after cessation of energy delivery was observed frequently. The mean maximal temperature was 40.8°C. Using a multiple regression analysis creating a box lesion that implies superior- and inferior lines at the posterior wall connecting the right and left encircling was an independent predictor of temperature. Six month follow-up showed an overall success rate of 78% documented as sinus rhythm in seven-day holter ECG. Conclusion Limitation of esophageal temperature to 40°C is associated with the lowest incidence of esophageal lesion formation published so far. This approach may contribute to increase the safety profile of radiofrequency ablation in the left atrium.

Organizational investment in human resource development (HRD) has risen rapidly over the years. The rise in HRD investment is undoubtedly triggered by the belief that HRD is the key to strengthening personal and organizational performance. Yet despite heavy investment in this area, the outcomes achieved are often mixed with varied results. A key issue is the choice of HRD initiatives adopted and how they are implemented to achieve the desired HRD outcomes. Poor initiatives that do not realistically target HRD gaps, combined with poor implementation measures, are most likely to fail. Regular measurement of such is significant not only to determine the impact on key outcomes but is also essential to learn, accumulate evidence, and then use such evidence for improving HRD investment and/or policy. The study's main objective is to analyse the training and development activities in PNG Power Limited (PPL) from the lenses of management and employees. This research highlights management and employees' involvement in HRD initiatives which is paramount for organisational development. The study employed a mixed method of analysis and used surveys and interviews to collect data and information. The findings revealed that PPL has organised training programs to develop management skills of non-technical staff and competency-based training for technical employees. However, these training and development activities are perceived to be moderately effective regarding how management and employees are involved. This research concludes that the effectiveness of HRD initiatives through training and development activities is significantly determined by the degree of management and employee involvement. This study contributes to the knowledge of HRD in developing countries, particularly in the Pacific Region. It is hoped that this study will be helpful to improve specific areas requiring change identified in this study and may well serve as inspiration for organisational and policy change across other service organisations in PNG.

Herein we report the use of Chaperonin-Containing TCP-1 (CCT or TRiC) as a marker to detect circulating tumor cells (CTCs) that are shed from tumors during oncogenesis. Most detection methods used in liquid biopsy approaches for enumeration of CTCs from blood, employ epithelial markers like cytokeratin (CK). However, such markers provide little information on the potential of these shed tumor cells, which are normally short-lived, to seed metastatic sites. To identify a marker that could go beyond enumeration and provide actionable data on CTCs, we evaluated CCT. CCT is a protein-folding complex composed of eight subunits. Previously, we found that expression of the second subunit (CCT2 or CCTβ) inversely correlated with cancer patient survival and was essential for tumorigenesis in mice, driving tumor-promoting processes like proliferation and anchorage-independent growth. In this study, we examined CCT2 expression in cancer compared to normal tissues and found statistically significant increases in tumors. Because not all blood samples from cancer patients contain detectable CTCs, we used the approach of spiking a known number of cancer cells into blood from healthy donors to test a liquid biopsy approach using CCT2 to distinguish rare cancer cells from the large number of non-cancer cells in blood. Using a clinically validated method for capturing CTCs, we evaluated detection of intracellular CCT2 staining for visualization of breast cancer and small cell lung (SCLC) cancer cells. We demonstrated that CCT2 staining could be incorporated into a CTC capture and staining protocol, providing biologically relevant information to improve detection of cancer cells shed in blood. These results were confirmed with a pilot study of blood from SCLC patients. Our studies demonstrate that detection of CCT2 could identify rare cancer cells in blood and has application in liquid biopsy approaches to enhance the use of minimally invasive methods for cancer diagnosis.

Business analytics can be described as the statistical analysis of data to make decisions and meaningful conclusions. As the demand to advance the curriculum of undergraduate business education increases, courses in business analytics aim to provide students with fundamental skills in critical thinking. Educators have found that spreadsheet applications that include statistical features are easy to use and facilitate student learning. The authors analyzed student performance in an introductory business analytics course that used Microsoft Excel as a statistical tool by comparing scores from this introductory course with those from an information technology course in which only Excel skills were learned.

Aim: To analyze trends in Utah melanoma diagnosis and study the impact of rurality. Patients & methods: State-wide melanoma incidence was calculated using Surveillance, Epidemiology, and End Results data (2005–2013). A subset of 5199 patients treated in an integrated healthcare system was further stratified for urban or rural residence. Results: Early-stage tumors accounted for most of the increase in melanoma incidence over time. Age-adjusted melanoma incidence rate was higher in rural counties (46.7 vs 39.4). Anatomic site and stage did not differ between rural and urban patients. Rural patients were more commonly diagnosed by a local primary care provider. Conclusion: Rurality had an impact on melanoma diagnosis in the specialty and location of the diagnosing provider.

The NHERI Lehigh Experimental Facility, as part of the NSF-funded Natural Hazards Engineering Research Infrastructure (NHERI) program, was established in 2016 as an open-access facility. This facility enables researchers to conduct state-of-art research on natural hazard mitigation in civil infrastructure systems, including high-performance numerical and physical testing to improve the resilience and sustainability of the civil infrastructure against natural hazards. The facility has the unique ability to conduct real-time multi-directional hybrid simulation (RTHS) on large-scale structural systems using 3D non-linear numerical models combined with large-scale physical models of structural and non-structural components. The Lehigh Experimental Facility possesses testbeds that include a lateral load-resisting system characterization testbed, a non-structural component multi-directional dynamic loading simulator, full-scale and reduced-scale damper testbeds, a tsunami and storm surge debris impact force testbed, and a soil-foundation structure interaction testbed. This paper describes the infrastructure and capabilities of the NHERI Lehigh Experimental Facility. Developments by the facility in advancing large-scale RTHS are detailed. Examples of research projects performed by users of the facility are then provided, including large-scale RTHS of steel frame buildings with magneto-rheological (MR) dampers and non-linear viscous dampers subject to strong earthquake ground motions; 3D multi-hazard large-scale RTHS of tall steel buildings subject to multi-directional wind and earthquake ground motions; characterization of a novel semi-active friction device based on band brake technology; and testing of cross-laminated timber self-centering coupled wall-floor diaphragm-gravity systems involving multi-directional loading.

This paper presents an experimental study on the multidirectional cyclic lateral-load response of post-tensioned self-centering (SC) cross-laminated timber (CLT) shear walls. SC-CLT shear wall damage states are introduced and qualitatively defined in terms of the repairs needed to restore the lateral-load response of the SC-CLT wall. A comparison between SC-CLT wall damage states under unidirectional (in-plane) and multidirectional (in-plane and out-of-plane) lateral loading is presented. The experimental results show that the initiation of SC-CLT wall damage occurs at smaller story drifts under multidirectional loading compared to unidirectional loading. Engineering demand parameters (EDPs) are used to quantify the SC-CLT wall damage states. Uncertainty in the EDP value when a damage state occurs is considered and quantified. Using the experimental results, component (i.e., a CLT wall panel corner) and system (i.e., an entire SC-CLT wall) fragility functions are developed and presented. [ABSTRACT FROM AUTHOR]

OBJECTIVES/GOALS: We recently identified a CA-MRSA strain in Brooklyn, New York (USA300-BKV) causing an outbreak of severe skin infections in predominantly healthy children. The evolution of USA300-BKV included acquisition of a novel prophage, and our objective is to identify the prophage-encoded gene(s) and mechanism responsible for increased bacterial virulence. METHODS/STUDY POPULATION: We deleted candidate genes from a novel mosaic block of phage-encoded genes in USA300-BKV that have been shown to enhance virulence in a murine skin infection model. Deletion mutants and complemented clones will be evaluated in vivo to identify culprit genes and determine the effect of lineage-specific genetic variation on the phenotype. Complementary studies include a comprehensive characterization of phage and bacterial genes expressed during lysogeny in vitro using RNA sequencing (RNA-Seq), and in vivo using a targeted approach focusing on known bacterial virulence and phage lytic pathways as well as candidate genes identified by in vitro studies. RESULTS/ANTICIPATED RESULTS: Comparison of otherwise isogenic lab strains showed that the mosaic block of phage genes present in USA300-BKV enhance skin abscess size in mice, confirming previous results. As this region of the phage, named mΦ11, does not contain known toxin genes, we hypothesize that mΦ11 modulates expression of bacterial host genes to enhance virulence. Thus, transcriptional profiles of CA-MRSA containing mΦ11 and selected deletion mutants are expected to reveal changes in known or novel virulence factors compared to controls. Candidate regulators specific to the mosaic block include an adenine methyltransferase linked to changes in global gene expression of other bacterial species. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results will broaden scientific understanding of phage-bacterial interactions and determine the mechanisms by which phage impact virulence independent from toxin gene carriage. Identification of phage-encoded gene(s) enhancing CA-MRSA contagion will inform surveillance efforts and identify novel therapeutic targets.

In light of the significant damage observed after earthquakes in Japan and New Zealand, enhanced performing seismic force‐resisting systems and energy dissipation devices are increasingly being utilized in buildings. Numerical models are needed to estimate the seismic response of these systems for seismic design or assessment. While there have been studies on modeling uncertainty, selecting the model features most important to response can remain ambiguous, especially if the structure employs less well‐established lateral force‐resisting systems and components. Herein, a global sensitivity analysis was used to address modeling uncertainty in specimens with elastic spines and force‐limiting connections (FLCs) physically tested at full‐scale at the E‐Defense shake table in Japan. Modeling uncertainty was addressed for both model class and model parameter uncertainty by varying primary models to develop several secondary models according to pre‐established uncertainty groups. Numerical estimates of peak story drift ratio and floor acceleration were compared to the results from the experimental testing program using confidence intervals and root‐mean‐square error. Metrics such as the coefficient of variation, variance, linear Pearson correlation coefficient, and Sobol index were used to gain intuition about each model feature's contribution to the dispersion in estimates of the engineering demands. Peak floor acceleration was found to be more sensitive to modeling uncertainty compared to story drift ratio. Assumptions for the spine‐to‐frame connection significantly impacted estimates of peak floor accelerations, which could influence future design methods for spines and FLC in enhanced lateral‐force resisting systems. [ABSTRACT FROM AUTHOR]

Acoustic emission (AE) testing is a widely used nondestructive testing (NDT) method to investigate material failure. When environmental conditions are harmful for the operation of the sensors, waveguides are typically mounted in between the inspected structure and the sensor. Such waveguides can be built from different materials or have different designs in accordance with the experimental needs. All these variations can cause changes in the acoustic emission signals in terms of modal conversion, additional attenuation or shift in frequency content. A finite element method (FEM) was used to model acoustic emission signal propagation in an aluminum plate with an attached waveguide and was validated against experimental data. The geometry of the waveguide is systematically changed by varying the radius and height to investigate the influence on the detected signals. Different waveguide materials were implemented and change of material properties as function of temperature were taken into account. Development of the option of modeling different waveguide options replaces the time consuming and expensive trial and error alternative of experiments. Thus, the aim of this research has important implications for those who use waveguides for AE testing.