Dr. Madalena Costa's career goal is to become an independent, academic investigator and faculty mentor. Her long-range goals are: (i) to understand basic mechanisms underlying nonlinear physiologic control in health and their degradation with aging and frailty, (ii) to develop a new class of dynamical biomarkers that quantify integrative physiologic function and give information about pathophysiology not obtainable with traditional probes, and (iii) to determine the value of the information encoded in the dynamical behavior of these biomarkers over time for risk stratification and the assessment of therapeutic interventions designed to reverse or retard pathologic aging. Her work is at the interdisciplinary interfaces of statistical physics, bioengineering, physiology, and the biology of aging. Two emerging themes of this interdisciplinary work are that healthy systems, which are marked by robustness and adaptability, exhibit the most complex multiscale dynamics, and that aging and the frailty syndrome in particular, are marked by a loss of complex multiscale variability and adaptive capacity. With the support of mentors, whose work spans diverse fields of biology, clinical medicine, physics, nonlinear dynamics and biostatistics that are essential facets of a broad-based training program, Dr. Costa proposes to pursue a career development plan that will enable her to further develop her expertise in complex systems in concert with state-of-the-art knowledge of the biology of aging and the clinical syndrome of frailty. Her basic research will address the following specific aims: 1) to elucidate nonlinear mechanisms of integrative physiologic control by developing dynamical biomarkers that quantify multiscale fluctuations;2) to test the hypothesis that the dynamical complexity of physiologic regulatory mechanisms degrades with aging in representative systems ranging from the cellular to organ, and 3) to test the hypothesis that loss of complexity in physiologic systems over time can be predictive of overall health status degradation and subsequent development of frailty. She will also use her experience to develop a training program in quantitative analysis of complex signals.

Public Health Relevance

This work is of importance because it uses novel approaches and technologies to address a major public health problem, namely frailty in the elderly, which affects millions of Americans and others worldwide and is responsible for substantial morbidity and mortality and for billions of dollars of healthcare costs.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Career Transition Award (K99)
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National Institute on Aging Initial Review Group (NIA)
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Joseph, Lyndon
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Beth Israel Deaconess Medical Center
United States
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Schnettler, William T; Goldberger, Ary L; Ralston, Steven J et al. (2016) Complexity analysis of fetal heart rate preceding intrauterine demise. Eur J Obstet Gynecol Reprod Biol 203:286-90
Costa, Madalena D; Henriques, Teresa; Munshi, Medha N et al. (2014) Dynamical glucometry: use of multiscale entropy analysis in diabetes. Chaos 24:033139
Costa, Madalena D; Schnettler, William T; Amorim-Costa, CĂ©lia et al. (2014) Complexity-loss in fetal heart rate dynamics during labor as a potential biomarker of acidemia. Early Hum Dev 90:67-71
Henriques, Teresa; Munshi, Medha N; Segal, Alissa R et al. (2014) ""Glucose-at-a-Glance"": New Method to Visualize the Dynamics of Continuous Glucose Monitoring Data. J Diabetes Sci Technol 8:299-306
Stirling, Leia A; Lipsitz, Lewis A; Qureshi, Mona et al. (2013) Use of a tracing task to assess visuomotor performance: effects of age, sex, and handedness. J Gerontol A Biol Sci Med Sci 68:938-45
Lim, Andrew S P; Yu, Lei; Costa, Madalena D et al. (2012) Increased fragmentation of rest-activity patterns is associated with a characteristic pattern of cognitive impairment in older individuals. Sleep 35:633-40B
Leistedt, S J-J; Linkowski, P; Lanquart, J-P et al. (2011) Decreased neuroautonomic complexity in men during an acute major depressive episode: analysis of heart rate dynamics. Transl Psychiatry 1:e27
Lim, Andrew S P; Yu, Lei; Costa, Madalena D et al. (2011) Quantification of the fragmentation of rest-activity patterns in elderly individuals using a state transition analysis. Sleep 34:1569-81
Burykin, Anton; Costa, Madalena D; Peng, Chung-Kang et al. (2011) Generating Signals with Multiscale Time Irreversibility: The Asymmetric Weierstrass Function. Complexity 16:29-38
Manor, Brad; Costa, Madalena D; Hu, Kun et al. (2010) Physiological complexity and system adaptability: evidence from postural control dynamics of older adults. J Appl Physiol 109:1786-91

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