ABSTRACT
There is an increasing backlog of potentially toxic compounds that cannot be evaluated with current animal-based approaches in a cost-effective and expeditious manner, thus putting human health at risk. Extrapolation of animal-based test results for human risk assessment often leads to different physiological outcomes. This article introduces the use of quantitative tools and methods from systems engineering to evaluate the risk of toxic compounds by the analysis of the amount of stress that human hepatocytes undergo in vitro when metabolizing GW7647 1 over extended times and concentrations. Hepatocytes are exceedingly connected systems that make it challenging to understand the highly varied dimensional genomics data to determine risk of exposure. Gene expression data of peroxisome proliferator-activated receptor-α (PPARα) 2 binding was measured over multiple concentrations and varied times of GW7647 exposure and leveraging mahalanombis distance to establish toxicity threshold risk levels. The application of these novel systems engineering tools provides new insight into the intricate workings of human hepatocytes to determine risk threshold levels from exposure. This approach is beneficial to decision makers and scientists, and it can help reduce the backlog of untested chemical compounds due to the high cost and inefficiency of animal-based models.
Subject(s)
Chemical Engineering/methods , Hepatocytes/drug effects , PPAR alpha/antagonists & inhibitors , Xenobiotics/pharmacology , Animals , Butyrates/pharmacology , Gene Expression Regulation , Hepatocytes/cytology , Hepatocytes/metabolism , Humans , Models, Biological , PPAR alpha/genetics , PPAR alpha/metabolism , Phenylurea Compounds/pharmacology , Protein Binding , Risk Assessment , Toxicogenetics/methodsABSTRACT
Coastal hazards including storm surge, sea-level rise, and cyclone winds continue to have devastating effects on infrastructure systems and communities despite costly investments in risk management. Risk management has generally not been sufficiently focused on coastal resilience, with community stakeholders involved in the process of making their coastline, as a system, more resilient to coastal storms. Thus, without stakeholder earlier involvement in coastal resilience planning for their community, they are frustrated after disasters occur. The U.S. National Academies has defined resilience as "the ability to prepare and plan for, absorb, recover from, and more successfully adapt to adverse events"(National Research Council). This article introduces a methodology for enabling stakeholder-involved resilience discussions across physical, information, cognitive, and social domains. The methodology addresses the stages of resilience-prepare, absorb, recover, and adapt-and integrates performance assessment with scenario analysis to characterize disruptions of risk-management priorities. The methodology is illustrated through a case study at Mobile Bay, Alabama, USA.
ABSTRACT
This study examines a new approach of using the Design Structure Matrix (DSM) modeling technique to improve the design of Electronic Medical Record (EMR) user interfaces. The usability of an EMR medication dosage calculator used for placing orders in an academic hospital setting was investigated. The proposed method captures and analyzes the interactions between user interface elements of the EMR system and groups elements based on information exchange, spatial adjacency, and similarity to improve screen density and time-on-task. Medication dose adjustment task time was recorded for the existing and new designs using a cognitive simulation model that predicts user performance. We estimate that the design improvement could reduce time-on-task by saving an average of 21 hours of hospital physicians' time over the course of a month. The study suggests that the application of DSM can improve the usability of an EMR user interface.
