I know that most men, including those at ease with the problems of the greatest complexity, can seldom accept even the simplest and most obvious truth if it be such as would oblige them to admit the falsity of conclusions which they have delighted in explaining to colleagues, which they have proudly taught to others, and which they have woven, thread by thread, into the fabric of their lives. Joseph Ford quoting Tolstoy (Gleick, 1987) We are used to thinking that natural objects have a certain form and that this form is determined by a characteristic scale. If we magnify the object beyond this scale, no new features are revealed. To correctly measure the properties of the object, such as length, area, or volume, we measure it at a resolution finer than the characteristic scale of the object. We expect that the value we measure has a unique value for the object. This simple idea is the basis of the calculus, Euclidean geometry, and the theory of measurement. However, Mandelbrot (1977, 1983) brought to the world's attention that many natural objects simply do not have this preconceived form. Many of the structures in space and processes in time of living things have a very different form. Living things have structures in space and fluctuations in time that cannot be characterized by one spatial or temporal scale. They extend over many spatial or temporal scales.

This exceptional book is concerned with the application of fractals and chaos, as well as other concepts from nonlinear dynamics to biomedical phenomena. Herein we seek to communicate the excitement being experienced by scientists upon making application of these concepts within the life sciences. Mathematical concepts are introduced using biomedical data sets and the phenomena being explained take precedence over the mathematics. In this new edition what has withstood the test of time has been updated and modernized; speculations that were not borne out have been expunged and the breakthroughs that have occurred in the intervening years are emphasized. The book provides a comprehensive overview of a nascent theory of medicine, including a new chapter on the theory of complex networks as they pertain to medicine.

Widespread chronic diseases (e.g., heart diseases, diabetes and its complications, stroke, cancer, brain diseases) constitute a significant cause of rising healthcare costs and pose a significant burden on quality-of-life for many individuals. Despite the increased need for smart healthcare sensing systems that monitor / measure patients’ body balance, there is no coherent theory that facilitates the modeling of human physiological processes and the design and optimization of future healthcare cyber-physical systems (HCPS). The HCPS are expected to mine the patient’s physiological state based on available continuous sensing, quantify risk indices corresponding to the onset of abnormality, signal the need for critical medical intervention in real-time by communicating patient’s medical information via a network from individual to hospital, and most importantly control (actuate) vital health signals (e.g., cardiac pacing, insulin level, blood pressure) within personalized homeostasis. To prevent health complications, maintain good health and/or avoid fatal conditions calls for a cross-disciplinary approach to HCPS design where recent statistical-physics inspired discoveries done by collaborations between physicists and physicians are shared and enriched by applied mathematicians, control theorists and bioengineers. This critical and urgent multi-disciplinary approach has to unify the current state of knowledge and address the following fundamental challenges: One fundamental challenge is represented by the need to mine and understand the complexity of the structure and dynamics of the physiological systems in healthy homeostasis and associated with a disease (such as diabetes). Along the same lines, we need rigorous mathematical techniques for identifying the interactions between integrated physiologic systems and understanding their role within the overall networking architecture of healthy dynamics. Another fundamental challenge calls for a deeper understanding of stochastic feedback and variability in biological systems and physiological processes, in particular, and for deciphering their implications not only on how to mathematically characterize homeostasis, but also on defining new control strategies that are accounting for intra- and inter-patient specificity – a truly mathematical approach to personalized medicine. Numerous recent studies have demonstrated that heart rate variability, blood glucose, neural signals and other interdependent physiological processes demonstrate fractal and non-stationary characteristics. Exploiting statistical physics concepts, numerous recent research studies demonstrated that healthy human physiological processes exhibit complex critical phenomena with deep implications for how homeostasis should be defined and how control strategies should be developed when prolonged abnormal deviations are observed. In addition, several efforts have tried to connect these fractal characteristics with new optimal control strategies that implemented in medical devices such as pacemakers and artificial pancreas could improve the efficiency of medical therapies and the quality-of-life of patients but neglecting the overall networking architecture of human physiology. Consequently, rigorously analyzing the complexity and dynamics of physiological processes (e.g., blood glucose and its associated implications and interdependencies with other physiological processes) represents a fundamental step towards providing a quantifiable (mathematical) definition of homeostasis in the context of critical phenomena, understanding the onset of chronic diseases, predicting deviations from healthy homeostasis and developing new more efficient medical therapies that carefully account for the physiological complexity, intra- and inter-patient variability, rather than ignoring it. This Research Topic aims to open a synergetic and timely effort between physicians, physicists, applied mathematicians, signal processing, bioengineering and biomedical experts to organize the state of knowledge in mining the complexity of physiological systems and their implications for constructing more accurate mathematical models and designing QoL-aware control strategies implemented in the new generation of HCPS devices. By bringing together multi-disciplinary researchers seeking to understand the many aspects of human physiology and its complexity, we aim at enabling a paradigm shift in designing future medical devices that translates mathematical characteristics in predictable mathematical models quantifying not only the degree of homeostasis, but also providing fundamentally new control strategies within the personalized medicine era.

On the Fractal Language of Medicine bridges a very clear gap among the knowledge gained over the last 20 years in the physical and life sciences on network theory, organ synchronicity and communication, the understanding of fractal signatures in health and disease and the importance of fractional calculus in integrating these concepts. The authors opine that the field of medicine has not appreciated this hard-won knowledge and has suffered greatly as a result. This book addresses this perceived deficiency by introducing medical researchers, clinicians, residents, first-year medical students and members of allied fields to the work of the so-called hard sciences. It seeks to facilitate effective communication between empiricists and theorists by making interdisciplinary efforts to explain complex mathematical concepts to physicians and, equally important, to elucidate complex medical concepts to physicists or mathematicians. This book will be of great interest to medical students, professionals and academics, as well as students and researchers of applied mathematics, especially those interested in fractional calculus and fractals.

This book provides a compilation of mathematical-computational tools that are used to analyze experimental data. The techniques presented are those that have been most widely and successfully applied to the analysis of physiological systems, and address issues such as randomness, determinism, dimension, and nonlinearity. In addition to bringing together the most useful methods, sufficient mathematical background is provided to enable non-specialists to understand and apply the computational techniques. Thus, the material will be useful to life-science investigators on several levels, from physiologists to bioengineer.Initial chapters present background material on dynamic systems, statistics, and linear system analysis. Each computational technique is demonstrated with examples drawn from physiology, and several chapters present case studies from oculomotor control, neuroscience, cardiology, psychology, and epidemiology. Throughout the text, historical notes give a sense of the development of the field and provide a perspective on how the techniques were developed and where they might lead. The overall approach is based largely on the analysis of trajectories in the state space, with emphasis on time-delay reconstruction of state-space trajectories. The goal of the book is to enable readers to apply these methods to their own research.

The biological basis of physiological signals is incredibly complex. While many types of research certainly appreciate molecular, cellular and systems approach to unravel overall biological complexity, in the recent decades the interest for mathematical and computational characterization of structural and functional basis underlying biological phenomena gain wide popularity among scientists. Nowadays, we witnessed wide range applications of nonlinear quantitative analysis that produced measures such as fractal dimension, power-law scaling, Hurst exponent, Lyapunov exponent, approximate entropy, sample entropy, Lempel–Ziv complexity, as well as other metrics for predictions of onset and progression of many pathological conditions, especially in the central nervous systems (CNS). In this Research Topic, we seek to bring together the recent practical and theoretical advances in the development and application of nonlinear methods or narrower fractal-based methods for characterizing the complex physiological systems at multiple levels of the organization. We will discuss the use of various complexity measures and appropriate parameters for characterizing the variety of physiological signals up to the systems level. There are multiple aims in this topic. The recent advancement in the application of nonlinear methods for both normal and pathological physiological conditions is the first. The second aim is to emphasize the more recent successful attempt to apply these methods across animal species. Finally, a comprehensive understanding of advantages and disadvantages of each method, especially between its mathematical assumptions and real-world applicability, can help to find out what is at stake regarding the above aims and to direct us toward the more fruitful application of nonlinear measures and statistics in physiology and biology in general.