The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.
Objective
The purpose of this study was to evaluate ICU nurses’ ability to detect patient change using an integrated graphical information display (IGID) versus a conventional tabular ICU patient information display (i.e. electronic chart).
Design
Using participants from two different sites, we conducted a repeated measures simulator-based experiment to assess ICU nurses’ ability to detect abnormal patient variables using a novel IGID versus a conventional tabular information display. Patient scenarios and display presentations were fully counterbalanced.
Measurements
We measured percent correct detection of abnormal patient variables, nurses’ perceived workload (NASA-TLX), and display usability ratings.
Results
32 ICU nurses (87% female, median age of 29 years, and median ICU experience of 2.5 years) using the IGID detected more abnormal variables compared to the tabular display [F (1,119)=13.0, p < 0.05]. There was a significant main effect of site [F (1, 119)=14.2], with development site participants doing better. There were no significant differences in nurses’ perceived workload. The IGID display was rated as more usable than the conventional display, [F (1, 60)=31.7].
Conclusion
Overall, nurses reported more important physiological information with the novel IGID than tabular display. Moreover, the finding of site differences may reflect local influences in work practice and involvement in iterative display design methodology. Information displays developed using user-centered design should accommodate the full diversity of the intended user population across use sites.
A graphic representation of monitored data may provide better support for detection, diagnosis, and treatment. A user-centered design process led to a novel object-oriented graphic display of hemodynamic variables containing emergent features and functional relationships. In a simulated environment, this display appeared to support clinicians' ability to diagnose, manage, and treat a critical cardiovascular event in a simulated environment. We designed a graphic display to show hemodynamic variables. The study provides some support for the hypothesis that providing clinical information graphically in a display designed with emergent features and functional relationships can improve clinicians' ability to detect, diagnosis, mange, and treat critical cardiovascular events in a simulated environment.
The drug display altered simulated clinical practice. These results, which will inform the next iteration of designs and evaluations, suggest promise for this approach to drug data visualization.
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