{"project":{"acronym":"","projectId":23211,"title":"Mathematical Modeling of Circadian/Performance Countermeasures","primaryTaxonomyNodes":[{"taxonomyNodeId":10695,"taxonomyRootId":8816,"parentNodeId":10693,"level":3,"code":"TX06.3.2","title":"Prevention and Countermeasures","definition":"Prevention and countermeasure tools validate technologies to address the effects of the space environment on human systems and countermeasures to maintain crew physical health, behavioral health, and sustained performance on extended-duration missions.","exampleTechnologies":"Cell/tissue culture, animal models; induced pluripotent stem cells; exercise equipment systems (hardware & software); integrated prevention and treatment for visual changes and non-invasive intracranial pressure measurement; water control standards for microbes, probiotic delivery, antimicrobial medications; integrated technologies to monitor crew health and performance during exercise; countermeasure effectiveness; vibration isolation technologies for exercise equipment","hasChildren":false,"hasInteriorContent":true}],"startTrl":4,"currentTrl":6,"endTrl":6,"benefits":"The development (1) of mathematical models of circadian rhythms, sleep, alertness, and performance and (2) of software based on these models that aid in schedule design can improve performance and alertness and thereby effectiveness and public safety for people who work at night, on rotating schedules, on non-24-hr schedules or extended duty schedules (pilots, train and truck drivers, shift workers, health care workers, public safety officers, etc.). Attempting to sleep at adverse circadian phases is difficult and sleep efficiency is poor. Attempting to work at adverse circadian phases and/or after long durations of time awake results in poor worker performance and productivity, increased accidents, and decreased safety for workers and for others affected by the workers. For example, the accidents at the Chernobyl and Three Mile Island nuclear reactors and the Exxon Valdez grounding all were partially caused by workers working at adverse circadian phases (~ 4 am). The mathematical modeling and the available Circadian Performance Simulation Software (CPSS) can be used to simulate and quantitatively evaluate different scenarios of sleep/wake schedules and light exposure to predict the resulting circadian phase and amplitude, subjective alertness, and performance. CPSS has been requested by members of academia, government, and industry (transportation (especially airline personnel), safety, medical, military). Its use could help produce improved schedules for working for people in space and on Earth. The software also now includes optimal countermeasure design, so that countermeasures can be planned for times of predicted poor performance and alertness. The schedule/countermeasure design program allows a user to interactively design a schedule and to automatically design a mathematically optimal countermeasure regime (intensity, duration, and placement). This will be valuable to those who schedule people who work at night, on rotating schedules, on non-24-hr schedules, or extended duty schedules. Individuals can design countermeasures for their assigned work schedules so that their sleep and wake rhythms will be adjusted for optimal performance at desired times. Using these tools, we have completed systematic simulation studies of the effect of circadian shifting on phase re-entrainment and performance recovery. For example, we examined the effect of light levels within cockpits and passenger cabins on circadian phase and performance during trans-meridian travel and polar flight paths for an article that appeared in The Wall Street Journal in 2004. The mathematical modeling has been used for basic scientific research. Inclusion of mathematical models in the planning process to optimize measures to be studied in experimental protocols enables more efficient use of research resources and directs new research. If the modeling of existing data is unsatisfactory, then the model assumptions need to be revised. This revision may include identification of a new physiological process not previously described. As an example, an additional component (non-linear response to ocular light stimuli) was added to the circadian rhythms component of our mathematical model to describe data collected in our clinical research facilities, even before the anatomic and physiologic basis of this component of the mathematical model was found. Later experiments validated this mathematical finding. The mathematical model had demonstrated that previously unknown additional physiological processes were involved. The modeling work on the differential effects of different wavelength of light on circadian rhythms and alertness can be used for designing artificial (indoor) lighting systems that can maximize circadian or alerting response. The mathematical modeling efforts and CPSS have also been used in educational programs and in the popular press to teach students and teachers about circadian rhythms and sleep and their effects on alertness and performance.","description":"
We developed and refined our current mathematical model of circadian rhythms to incorporate melatonin as a marker rhythm. We used an existing physiologically based mathematical model of the diurnal variations in plasma melatonin levels. The revised model can predict melatonin amplitude, markers of melatonin phase (melatonin synthesis onset (Synon) and synthesis offset (Synoff)), melatonin suppression by light, and salivary melatonin concentrations. Our model has been validated on several independent data sets. A manuscript of this work has been published. We incorporated wavelength sensitivity into our current mathematical model. We have revised the light input to our model from lux to an irradiance measure (microW/cm2) for both polychromatic and monochromatic light exposures. We have developed a two-channel photoreceptor model, in which one channel is driven by rod/cone input and the other channel is driven by a melanopsin input with peak sensitivity in the short wavelength range (~480nm). Our model can predict the response of the circadian pacemaker to 1-pulse light exposures of 460nm and 555nm at different irradiances to generate fluence-response curves of circadian phase-shifts to polychromatic light. This work has been presented at scientific meetings. A manuscript of this work is in preparation. We developed schedule assessment and countermeasure design software. We have developed a schedule/countermeasure design program that allows a user to interactively design a schedule and to automatically design a mathematically optimal countermeasure regime (intensity, duration, and placement). We have demonstrated this tool to NASA personnel. We have substantially redesigned the user interface for CPSS, the software implementation of our mathematical model, based on feedback from NASA users and operational requirements. We have shown that our methods can be used to design a variety of schedules and countermeasures relevant to NASA operations including shifting sleep wake (slam shifting), sleep deprivation, and non-24 hour schedules. This work has been presented at scientific meetings. A manuscript is in progress. We have begun to explore inter-individual differences in performance. (1) We have begun developing methodologies for determining how optimal model structure may differ by individual. The benefit of the framework is that models are easily understandable by non-mathematicians and that the probability distributions can be approximated by existing data. (2) We have conducted data analysis to quantify differences in model parameter values and we have correlated these model parameter differences with individual characteristics such as age, gender, morningness-eveningness, habitual bedrest duration, and habitual sleep/wake times. We have demonstrated the trait-like characteristics in the robustness of parameters associated with the homeostatic process under experimental light interventions. This work has been presented at scientific meetings.
","destinations":[{"lkuCodeId":1544,"code":"MOON_AND_CISLUNAR","description":"Moon and Cislunar","lkuCodeTypeId":526,"lkuCodeType":{"codeType":"DESTINATION_TYPE","description":"Destination Type"}},{"lkuCodeId":1518,"code":"MARS","description":"Mars","lkuCodeTypeId":526,"lkuCodeType":{"codeType":"DESTINATION_TYPE","description":"Destination Type"}}],"startYear":2004,"startMonth":6,"endYear":2008,"endMonth":8,"statusDescription":"Completed","principalInvestigators":[{"contactId":138191,"canUserEdit":false,"firstName":"Elizabeth","lastName":"Klerman","fullName":"Elizabeth B Klerman","fullNameInverted":"Klerman, Elizabeth B","middleInitial":"B","primaryEmail":"ebklerman@hms.harvard.edu","publicEmail":false,"nacontact":false}],"programDirectors":[{"contactId":103847,"canUserEdit":false,"firstName":"David","lastName":"Baumann","fullName":"David K Baumann","fullNameInverted":"Baumann, David K","middleInitial":"K","primaryEmail":"david.k.baumann@nasa.gov","publicEmail":true,"nacontact":false}],"programExecutives":[{"contactId":56,"canUserEdit":false,"firstName":"Stephen","lastName":"Davison","fullName":"Stephen C Davison","fullNameInverted":"Davison, Stephen C","middleInitial":"C","primaryEmail":"stephen.c.davison@nasa.gov","publicEmail":true,"nacontact":false}],"website":"https://taskbook.nasaprs.com","libraryItems":[{"files":[],"id":25406,"title":"Abstracts for Journals and Proceedings","description":"St Hilarie M, Gronfier C, Klerman EB. \"Addition of a light effect to a physiologically-based model of melatonin.\" SLEEP 2006: 20th Anniversary Meeting of the Associated Professional Sleep Societies, Salt Lake City, Utah, June 17 - 22, 2006. 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Program and Abstracts, 11th Biennial Meeting of the Society for Research in Biological Rhythms, Destin, FL, May 17-21, 2008. p. 135-136., May-2008","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":24986,"title":"Abstracts for Journals and Proceedings","description":"Thompson P, Klerman EB, Dean DA 2nd. \"Identifying two-process performance models using limited data.\" Society for Industrial and Applied Mathematics - Society for Mathematical Biology (SIAM-SMB) Joint Session on the Life Sciences, Raleigh, NC, July 31-August 4, 2006. Society for Industrial and Applied Mathematics - Society for Mathematical Biology (SIAM-SMB) Joint Session on the Life Sciences. In Press, June 2006., Jun-2006","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25500,"title":"Abstracts for Journals and Proceedings","description":"St Hilarie M, Klerman EB. \"A tool to analyze melatonin phase and amplitude using a physiologically based model of melatonin.\" SLEEP 2006: 20th Anniversary Meeting of the Associated Professional Sleep Societies, Salt Lake City, Utah, June 17 - 22, 2006. Sleep. In Press, 2006., Apr-2006","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25834,"title":"Abstracts for Journals and Proceedings","description":"Dean DA 2nd, Barger LK, Livingston G, Klerman EB. \"Using Bayesian Networks to understand individual differences that affect the use of actigraphy as a predictor of sleep.\" SLEEP 2006: 20th Anniversary Meeting of the Associated Professional Sleep Societies, Salt Lake City, Utah, June 17 - 22, 2006. Sleep. In Press, 2006., Apr-2006","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25792,"title":"Abstracts for Journals and Proceedings","description":"St Hilarie M, Klerman EB. \"A tool to analyze melatonin phase and amplitude using a physiologically based model of melatonin.\" Sleep 2006, 20th Anniversary Meeting of the Association of Professional Sleep Societies, Salt Lake City, UT, June 17-22, 2006. 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Society for Industrial and Applied Mathematics - Society for Mathematical Biology (SIAM-SMB) Joint Session on the Life Sciences, in press June 2006., Jun-2006","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25497,"title":"Abstracts for Journals and Proceedings","description":"Dean DA 2nd, Forger DB, Klerman EB. \"Designing optimal light intervention schedules for experimental and operational settings.\" Associated Professional Sleep Societies 19th Annual Meeting, Denver, Colorado, June 18-23, 2005. Sleep. 2005;28A:A69., Jun-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":8275,"title":"Abstracts for Journals and Proceedings","description":"Dean DA, Wyatt JK, Dijk D, Czeisler CA, Klerman EB. \"Quantifying practice effects within groups and individuals: examples from a month long forced desynchrony protocol.\" Sleep 2008, Baltimore, MD, June 7-12, 2008. Sleep. 2008;31 Suppl:A54., Jun-2008","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25743,"title":"Abstracts for Journals and Proceedings","description":"Dean DA 2nd, Barger LK, Livingston G, Klerman EB. \"Understanding Bayesian network sensitivity in classifiers derived from human experimental data.\" Life Science Society Computational Systems Bioinformatics Conference. Stanford, CA, 2006 August. Life Science Society Computational Systems Bioinformatics Conference. Submitted for Publication, 2006 August., Aug-2006","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25768,"title":"Abstracts for Journals and Proceedings","description":"Klerman EB, Dean DA 2nd, Gurdziel K, St Hilaire M, Kronauer RE. \"Mathematical modeling of human circadian physiology applications in space and for the general public.\" 15th International Academy of Astronautics Humans in Space Symposium, Graz, Austria, 2005 May. 15th International Academy of Astronautics Humans in Space Symposium, 2005 May., May-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25389,"title":"Abstracts for Journals and Proceedings","description":"St Hilaire MA, Klerman EB, Lockley SW, Brainard GC, Kronauer RE. \"Revision of a mathematical model of circadian photic resetting to incorporate spectral sensitivity.\" Associated Professional Sleep Societies 19th Annual Meeting, Denver, Colorado, June 18-23, 2005. Sleep. 2005;28A:A56., Jun-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":8273,"title":"Abstracts for Journals and Proceedings","description":"St. Hilaire MA, Klerman EB. \"Robustness of parameters in a circadian and neurobehavioral performance and alertness model suggest trait-like characteristics of the homestatic process.\" Sleep 2008, Baltimore, MD, June 7-12, 2008. Sleep. 2008;31 Suppl:A117., Jun-2008","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":26159,"title":"Abstracts for Journals and Proceedings","description":"Dean DA 2nd, Klerman EB. \"Using domain specific information to design optimal circadian adjustment schedules.\" 35th International Congress of Physiological Sciences, March 2005. 35th International Congress of Physiological Sciences, 2005., Mar-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":26207,"title":"Articles in Peer-reviewed Journals","description":"Klerman EB, Hilaire MS. \"On mathematical modeling of circadian rhythms, performance, and alertness.\" J Biol Rhythms. 2007 Apr;22(2):91-102. Review. http://dx.doi.org/10.1177/0748730407299200 ; PMID: 17440211 , Apr-2007","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25331,"title":"Articles in Peer-reviewed Journals","description":"Klerman EB. \"Clinical aspects of human circadian rhythms.\" J Biol Rhythms. 2005 Aug;20(4):375-86. Review. PMID: 16077156 , Aug-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":8272,"title":"Articles in Peer-reviewed Journals","description":"St Hilaire MA, Gronfier C, Zeitzer JM, Klerman EB. \"A physiologically based mathematical model of melatonin including ocular light suppression and interactions with the circadian pacemaker.\" J Pineal Res. 2007 Oct;43(3):294-304. http://dx.doi.org/10.1111/j.1600-079X.2007.00477.x ; PMID: 17803528, Oct-2007","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":8271,"title":"Articles in Peer-reviewed Journals","description":"St Hilaire MA, Klerman EB, Khalsa SB, Wright KP Jr, Czeisler CA, Kronauer RE. \"Addition of a non-photic component to a light-based mathematical model of the human circadian pacemaker.\" J Theor Biol. 2007 Aug 21;247(4):583-99. http://dx.doi.org/10.1016/j.jtbi.2007.04.001 ; PMID: 17531270, Aug-2007","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":8270,"title":"Articles in Peer-reviewed Journals","description":"Klerman EB, Hilaire MS. \"On mathematical modeling of circadian rhythms, performance, and alertness.\" J Biol Rhythms. 2007 Apr;22(2):91-102. http://dx.doi.org/10.1177/0748730407299200 ; PMID: 17440211, Apr-2007","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25830,"title":"Articles in Peer-reviewed Journals","description":"Indic P, Gurdziel K, Kronauer RE, Klerman EB. \"Development of a two-dimension manifold to represent high dimension mathematical models of the intracellular Mammalian circadian clock.\" J Biol Rhythms. 2006 Jun;21(3):222-32. PMID: 16731662 , Jun-2006","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":24948,"title":"Articles in Peer-reviewed Journals","description":"Dean DA 2nd, Adler GK, Nguyen DP, Klerman EB. \"Biological time series analysis using a context free language: applicability to pulsatile hormone data.\" PLoS One. 2014 Sep 3;9(9):e104087. eCollection 2014. http://dx.doi.org/10.1371/journal.pone.0104087 ; PubMed PMID: 25184442; PubMed Central PMCID: PMC4153563, Sep-2014","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25700,"title":"Articles in Peer-reviewed Journals","description":"Indic P, Forger DB, St Hilaire MA, Dean DA 2nd, Brown EN, Kronauer RE, Klerman EB, Jewett ME. \"Comparison of amplitude recovery dynamics of two limit cycle oscillator models of the human circadian pacemaker.\" Chronobiol Int. 2005;22(4):613-29. PMID: 16147894, Sep-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":24971,"title":"Articles in Peer-reviewed Journals","description":"Kronauer RE, Gunzelmann G, Van Dongen HP, Doyle FJ 3rd, Klerman EB. \"Uncovering physiologic mechanisms of circadian rhythms and sleep/wake regulation through mathematical modeling.\" J Biol Rhythms. 2007 Jun;22(3):233-45. Review. PMID: 17517913, Jun-2007","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25064,"title":"Articles in Peer-reviewed Journals","description":"Dean DA 2nd, Fletcher A, Hursh SR, Klerman EB. \"Developing mathematical models of neurobehavioral performance for the “real world“.\" J Biol Rhythms. 2007 Jun;22(3):246-58. Review. PMID: 17517914, Jun-2007","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25463,"title":"Articles in Peer-reviewed Journals","description":"Indic P, Gurdziel K, Kronauer RE, Klerman EB. \"Development of a two-dimension manifold to represent high dimension mathematical models of the intracellular Mammalian circadian clock.\" J Biol Rhythms. 2006 Jun;21(3):222-32. PMID: 16731662, Jun-2006","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25850,"title":"Awards","description":"Dean DA 2nd. \"Mr. Dean (graduate student) designated a Partners Healthcare scholar and awarded an Association of Multi-cultural Members at Partners Educational Scholarship, 2005.\" May-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":25631,"title":"Awards","description":"Dean DA 2nd. \"Mr. Dean (graduate student) received Travel Sponsorship to attend Case Studies in Bayesian Statistics 8, a nationally recognized conference that reviews applications of Bayesian statistics, September 2005.\" Sep-2005","libraryItemTypeId":1091,"projectId":23211,"primary":false,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}}],"transitions":[{"transitionId":6775,"projectId":23211,"partner":"Other","transitionDate":"2008-08-01","infusion":"Other","path":"Closed Out","details":"We developed and refined our current mathematical model of circadian rhythms to incorporate melatonin as a marker rhythm. We used an existing physiologically based mathematical model of the diurnal variations in plasma melatonin levels. The revised model can predict melatonin amplitude, markers of melatonin phase (melatonin synthesis onset (Synon) and synthesis offset (Synoff)), melatonin suppression by light, and salivary melatonin concentrations. Our model has been validated on several independent data sets. A manuscript of this work has been published. We incorporated wavelength sensitivity into our current mathematical model. We have revised the light input to our model from lux to an irradiance measure (microW/cm2) for both polychromatic and monochromatic light exposures. We have developed a two-channel photoreceptor model, in which one channel is driven by rod/cone input and the other channel is driven by a melanopsin input with peak sensitivity in the short wavelength range (~480nm). Our model can predict the response of the circadian pacemaker to 1-pulse light exposures of 460nm and 555nm at different irradiances to generate fluence-response curves of circadian phase-shifts to polychromatic light. This work has been presented at scientific meetings. A manuscript of this work is in preparation. We developed schedule assessment and countermeasure design software. We have developed a schedule/countermeasure design program that allows a user to interactively design a schedule and to automatically design a mathematically optimal countermeasure regime (intensity, duration, and placement). We have demonstrated this tool to NASA personnel. We have substantially redesigned the user interface for CPSS, the software implementation of our mathematical model, based on feedback from NASA users and operational requirements. We have shown that our methods can be used to design a variety of schedules and countermeasures relevant to NASA operations including shifting sleep wake (slam shifting), sleep deprivation, and non-24 hour schedules. This work has been presented at scientific meetings. A manuscript is in progress. We have begun to explore inter-individual differences in performance. (1) We have begun developing methodologies for determining how optimal model structure may differ by individual. The benefit of the framework is that models are easily understandable by non-mathematicians and that the probability distributions can be approximated by existing data. (2) We have conducted data analysis to quantify differences in model parameter values and we have correlated these model parameter differences with individual characteristics such as age, gender, morningness-eveningness, habitual bedrest duration, and habitual sleep/wake times. We have demonstrated the trait-like characteristics in the robustness of parameters associated with the homeostatic process under experimental light interventions. This work has been presented at scientific meetings.","rationale":"Other","infoText":"Closed out","infoTextExtra":"","dateText":"August 2008"}],"responsibleMd":{"acronym":"SOMD","canUserEdit":false,"city":"","external":false,"linkCount":0,"organizationId":9526,"organizationName":"Space Operations Mission Directorate","organizationType":"NASA_Mission_Directorate","naorganization":false,"organizationTypePretty":"NASA Mission Directorate"},"program":{"acronym":"HRP","active":true,"description":"Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance standards by the Office of the Chief Health and Medical Officer (OCHMO) and 2) provides Human Exploration Operations Mission Directorate (HEOMD) with methods of meeting those standards in the design, development, and operation of mission systems.
HRP research focuses on reducing crew health and performance risks for exploration missions. In addition, HRP research gathers the data necessary to understand and mitigate the long-term health risks to the crew, to allow the update of specific crew health standards for each mission scenario, to support crew selection, and to address any rehabilitation requirements. The OCHMO owns and sets the standards upon which the HRP research efforts are based. The Transition to Medical Practice process defined by the OCHMO is used to review the HRP deliverable countermeasures and technologies prior to their operational use.
HRP technology development advances medical care and countermeasure systems for exploration and vehicle development programs’ missions. The HRP also develops and matures operational concepts to inform requirements for the design and operation of space vehicles and habitats needed for exploration. This includes requirements for displays and controls, internal environments, operations planning, habitability, and methodologies for maintaining crew physical and mental health as well as physical and cognitive capabilities.
The HRP is managed at the Johnson Space Center (JSC) and comprised of six research and technology development projects. These projects provide the program knowledge and capabilities to conduct research addressing the human health and performance risks as well as advancing the readiness levels of technology and countermeasures to the point of transfer to the customer programs and organizations. The six projects within the HRP are referred to as Program Elements throughout this document. Each Element is managed at the JSC with research and technology development expertise provided by JSC, Ames Research Center (ARC), Glenn Research Center (GRC), the Langley Research Center (LaRC), and the Kennedy Space Center (KSC), as well as other Agencies, institutions and organizations identified in the following Element descriptions. The six Elements are:
1) Space Radiation (SR) Element – The SR Element performs investigations to develop the scientific basis to accurately predict and mitigate health risks from the space radiation environment. This knowledge yields recommendations to permissible exposure limits, assessment/projection tools/models of crew risk from radiation exposure, and models/tools to assess vehicle design for radiation protection. The SR Element conducts research using accelerator-based simulation of space radiation. The SR Element explores and develops countermeasures to the deleterious effects of radiation on human health. The LaRC and ARC contribute to the SR Element.
2) Behavioral Health and Performance (BHP) Element – The BHP Element identifies and characterizes the behavioral and performance risks associated with training, living and working in space, and returning to Earth. The BHP Element develops strategies, tools, and technologies to mitigate these risks.
3) Exploration Medical Capability (ExMC) Element – The ExMC Element is responsible for defining requirements for crew health maintenance during exploration missions, developing treatment scenarios, extrapolating from the scenarios to health management modalities, and evaluating the feasibility of those modalities for use during exploration missions. The ExMC Element is also responsible for the technology and informatics development that will enable the availability of medical care and decision systems for exploration missions. GRC, LaRC and ARC contribute technology development and clinical care expertise to the ExMC Element.
4) Space Human Factors and Habitability (SHFH) Element – The SHFH Element is focused on the human system in space environments: how do humans interface with spacecraft systems, and what environmental and habitation factors are essential to maintain crew health and performance? The SHFH Element has three main focus areas: space human factors engineering, advanced environmental health, and advanced food technology. The ARC contributes to the SHFH Element.
5) Human Health Countermeasures (HHC) Element – The HHC Element is responsible for understanding the physiological effects of spaceflight and developing countermeasure strategies and procedures. The Element provides the biomedical expertise for the development and assessment of medical standards and vehicle and spacesuit requirements dictated by human physiological needs. In addition, the HHC Element develops a validated and integrated suite of countermeasures for exploration missions to ensure the maintenance of crew health during all mission phases. The ARC and GRC contribute to the HHC Element as well as international agencies cooperating on joint flight proposals, reduced gravity studies, and collaborative bed rest studies.
6) International Space Station Medical Projects (ISSMP) Element – The ISSMP Element is responsible for managing all ISS and ground analog human research activities, including those integrated with operational medical support of the crews, and to ensure research tasks are completed. The ISSMP is responsible for all planning, integration, and implementation services for HRP research tasks and evaluation activities requiring access to space or related flight resources on the ISS, Soyuz, Progress, Multi-Purpose Crew Vehicle (MPCV), commercial vehicles and ground-based spaceflight analogs. This includes support to related pre- and postflight activities. The ARC contributes to the ISSMP with technical support to experiment management, hardware development, and international partner integration. KSC provides support for baseline data collection requirements development for future crew vehicles.
The work performed within the six Elements is supported by numerous collaborative efforts with academia and international agencies. Relationships with the ISS Program, the National Space Biomedical Research Institute (NSBRI), the Brookhaven National Laboratory (BNL), and the University of Texas Medical Branch (UTMB) are critical to the HRP successfully meeting its objectives. The HRP also maintains collaborative relationships with the International Partners through various working groups. These relationships enhance the research capabilities and provide synergy between the research and technology efforts of different countries.
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