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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.

Bacterial flagella are rotary nanomachines that contribute to bacterial fitness in many settings, including host colonization. The flagellar motor relies on the multiprotein flagellar motor-switch complex to govern flagellum formation and rotational direction. Different bacteria exhibit great diversity in their flagellar motors. One such variation is exemplified by the motor-switch apparatus of the gastric pathogen Helicobacter pylori, which carries an extra switch protein, FliY, along with the more typical FliG, FliM, and FliN proteins. All switch proteins are needed for normal flagellation and motility in H. pylori, but the molecular mechanism of their assembly is unknown. To fill this gap, we examined the interactions among these proteins. We found that the C-terminal SpoA domain of FliY (FliYC) is critical to flagellation and forms heterodimeric complexes with the FliN and FliM SpoA domains, which are β-sheet domains of type III secretion system proteins. Surprisingly, unlike in other flagellar switch systems, neither FliY nor FliN self-associated. The crystal structure of the FliYC-FliNC complex revealed a saddle-shaped structure homologous to the FliN-FliN dimer of Thermotoga maritima, consistent with a FliY-FliN heterodimer forming the functional unit. Analysis of the FliYC-FliNC interface indicated that oppositely charged residues specific to each protein drive heterodimer formation. Moreover, both FliYC-FliMC and FliYC-FliNC associated with the flagellar regulatory protein FliH, explaining their important roles in flagellation. We conclude that H. pylori uses a FliY-FliN heterodimer instead of a homodimer and creates a switch complex with SpoA domains derived from three distinct proteins.

A new floor connecting system developed for low-damage seismic-resistant building structures is described herein. The system, termed Inertial Force-Limiting Floor Anchorage System (IFAS), is intended to limit the lateral forces in buildings during an earthquake. This objective is accomplished by providing limited-strength deformable connections between the floor system and the primary elements of the lateral force-resisting system. The connections transform the seismic demands from inertial forces into relative displacements between the floors and lateral force-resisting system. This paper presents the IFAS performance in a shake-table testing program that provides a direct comparison with an equivalent conventional rigidly anchored-floor structure. The test structure is a half-scale, 4-story reinforced concrete flat-plate shear wall structure. Precast hybrid rocking walls and special precast columns were used for test repeatability in a 22-input strong ground-motion sequence. The structure was purposely designed with an eccentric wall layout to examine the performance of the system in coupled translational-torsional response. The test results indicated a seismic demand reduction in the lateral force-resisting system of the IFAS structure relative to the conventional structure, including reduced shear wall base rotation, shear wall and column inter-story drift, and, in some cases, floor accelerations. These results indicate the potential for the IFAS to minimize damage to the primary structural and non-structural components during earthquakes.

This paper presents experimental and numerical studies of a full-scale deformable connection used to connect the floor system of the flexible gravity load resisting system to the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. The purpose of the deformable connection is to limit the earthquake-induced horizontal inertia force transferred from the floor system to the LFRS and thereby to reduce the horizontal floor accelerations and the forces in the LFRS. The deformable connection that was studied consists of a friction device (FD) and carbon fiber-reinforced laminated low-damping rubber bearings (RB), denoted as the FD + RB connection. The test results show that the force-deformation responses of the FD + RB connection are stable under quasi-static sinusoidal and earthquake loading histories and dynamic sinusoidal loading histories. The FD + RB connection force-deformation response is approximated with a bilinear elastic-plastic force-deformation response with kinematic hardening. The FD is axially stiff, compact, easy-to-assemble, and able to accommodate the FD + RB connection kinematic requirements. The FD elastic stiffness controls the FD + RB connection elastic stiffness. The FD friction force controls the force when the FD + RB connection force-deformation response transitions from elastic to post elastic. The RB provide predictable and reliable post-elastic stiffness to the FD + RB connection. The machining tolerances for the FD components, the “break-in” effect, the sliding history, and the dwell time affect the FD friction force. Numerical simulation results for a 12-story reinforced concrete wall building with FD + RB connections under seismic loading show that a reduction of the FD friction force increases the FD + RB connection deformation demand.

This paper presents experimental and numerical studies of a full-scale deformable connection used to connect the floor system of the flexible gravity load resisting system to the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. The purpose of the deformable connection is to limit the earthquake-induced horizontal inertia force transferred from the floor system to the LFRS and, thereby, to reduce the horizontal floor accelerations and the forces in the LFRS. The deformable connection that was studied consists of a buckling-restrained brace (BRB) and steel-reinforced laminated low-damping rubber bearings (RB). The test results show that the force–deformation responses of the connection are stable, and the dynamic force responses are larger than the quasi-static force responses. The BRB+RB force–deformation response depends mainly on the BRB response. A detailed discussion of the BRB experimental force–deformation response is presented. The experimental results show that the maximum plastic deformation range controls the isotropic hardening of the BRB. The hardened BRB force–deformation responses are used to calculate the overstrength adjustment factors. Details and limitations of a validated, accurate model for the connection force–deformation response are presented. Numerical simulation results for a 12-story reinforced concrete wall building with deformable connections show the effects of including the RB in the deformable connection and the effect of modeling the BRB isotropic hardening on the building seismic response. Copyright © 2016 John Wiley & Sons, Ltd.

The human pathogen Helicobacter pylori uses the host receptor α5β1 integrin to trigger inflammation in host cells via its cag pathogenicity island (cag PAI) type IV secretion system (T4SS). Here, we report that the H. pylori ImaA protein (HP0289) decreases the action of the cag PAI T4SS via tempering the bacterium's interaction with α5β1 integrin. Previously, imaA-null mutants were found to induce an elevated inflammatory response that was dependent on the cag PAI T4SS; here we extend those findings to show that the elevated response is independent of the CagA effector protein. To understand how ImaA could be affecting cag PAI T4SS activity at the host cell interface, we utilized the Phyre structural threading program and found that ImaA has a region with remote homology to bacterial integrin-binding proteins. This region was required for ImaA function. Unexpectedly, we observed that imaA mutants bound higher levels of α5β1 integrin than wild-type H. pylori, an outcome that required the predicted integrin-binding homology region of ImaA. Lastly, we report that ImaA directly affected the amount of host cell β1 integrin but not other cellular integrins. Our results thus suggest a model in which H. pylori employs ImaA to regulate interactions between integrin and the T4SS and thus alter the host inflammatory strength.

This paper presents the development of a deformable connection that is used to connect each floor system of the flexible gravity load resisting system (GLRS) with the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. It is shown that the deformable connection acts as a seismic response modification device, which limits the lateral forces transferred from each floor to the LFRS and allows relative motion between the GLRS and LFRS. In addition, the floor accelerations and the LFRS story shears related to the higher-mode responses are reduced. The dispersion of peak responses is also significantly reduced. Numerical simulations of the earthquake response of a 12-story reinforced concrete shear wall example building with deformable connections are used to define an approximate feasible design space for the deformable connection. The responses of the example building model with deformable connections and the example building model with rigid-elastic connections are compared. Two configurations of the deformable connection are studied. In one configuration, a buckling restrained brace is used as the limited-strength load-carrying hysteretic component of the deformable connection, and in the other configuration, a friction device is used. Low damping laminated rubber bearings are used in both configurations to ensure the out-of-plane stability of the LFRS and to provide post-elastic stiffness to the deformable connection. Important experimental results from full-scale tests of the deformable connections are presented and used to calibrate numerical models of the connections. Copyright © 2016 John Wiley & Sons, Ltd.

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.