Work-related operations requiring extended wake durations, night, or rotating shifts negatively affect worker neurobehavioral performance and health. These types of work schedules are required in ...many industries, including the military, transportation, and health care. These industries are increasingly using or considering the use of mathematical models of neurobehavioral performance as a means to predict the neurobehavioral deficits due to these operational demands, to develop interventions that decrease these deficits, and to provide additional information to augment existing decision-making processes. Recent advances in mathematical modeling have allowed its application to real-world problems. Developing application-specific expertise is necessary to successfully apply mathematical models, in part because development of new algorithms and methods linking the models to the applications may be required. During a symposium, “Modeling Human Neurobehavioral Performance II: Towards Operational Readiness,” at the 2006 SIAM-SMB Conference on the Life Sciences, examples of the process of applying mathematical models, including model construction, model validation, or developing model-based interventions, were presented. The specific applications considered included refining a mathematical model of sleep/wake patterns of airline flight crew, validating a mathematical model using railroad operations data, and adapting a mathematical model to develop appropriate countermeasure recommendations based on known constraints. As mathematical models and their associated analytical methods continue to transition into operational settings, such additional development will be required. However, major progress has been made in using mathematical model outputs to inform those individuals making schedule decisions for their workers.
We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among ...researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials.
At an organism level, the mammalian circadian pacemaker is a two-dimensional system. For these two dimensions, phase (relative timing) and amplitude of the circadian pacemaker are commonly used. Both ...the phase and the amplitude (A) of the human circadian pacemaker can be observed within multiple physiological measures-including plasma cortisol, plasma melatonin, and core body temperature (CBT)-all of which are also used as markers of the circadian system. Although most previous work has concentrated on changes in phase of the circadian system, critically timed light exposure can significantly reduce the amplitude of the pacemaker. The rate at which the amplitude recovers to its equilibrium level after reduction can have physiological significance. Two mathematical models that describe the phase and amplitude dynamics of the pacemaker have been reported. These models are essentially equivalent in predictions of phase and in predictions of amplitude recovery for small changes from an equilibrium value (A=1), but are markedly different in the prediction of recovery rates when A<0.6. To determine which dynamic model best describes the amplitude recovery observed in experimental data; both models were fit to CBT data using a maximum likelihood procedure and compared using Akaike's Information Criterion (AIC). For all subjects, the model with the lower recovery rate provided a better fit to data in terms of AIC, supporting evidence that the amplitude recovery of the endogenous pacemaker is slow at low amplitudes. Experiments derived from model predictions are proposed to test the influence of low amplitude recovery on the physiological and neurobehavioral functions.
Circadian rhythms are endogenous rhythms with a cycle length of approximately 24 h. Rhythmic production of specific proteins within pacemaker structures is the basis for these physiological and ...behavioral rhythms. Prior work on mathematical modeling of molecular circadian oscillators has focused on the fruit fly, Drosophila melanogaster. Recently, great advances have been made in our understanding of the molecular basis of circadian rhythms in mammals. Mathematical models of the mammalian circadian oscillator are needed to piece together diverse data, predict experimental results, and help us understand the clock as a whole. Our objectives are to develop mathematical models of the mammalian circadian oscillator, generate and test predictions from these models, gather information on the parameters needed for model development, integrate the molecular model with an existing model of the influence of light and rhythmicity on human performance, and make models available in BioSpice so that they can be easily used by the general community. Two new mammalian models have been developed, and experimental data are summarized. These studies have the potential to lead to new strategies for resetting the circadian clock. Manipulations of the circadian clock can be used to optimize performance by promoting alertness and physiological synchronization.