In its extensively revised and updated Second Edition, this book provides a solid foundation for readers interested in clinical research. Discussion encompasses genetic, pharmacoepidemiologic and implementation research.

All chapters have been updated with new information and many new tables have been added to elucidate key points. The book now offers discussion on how to handle missing data when analyzing results, and coverage of Adaptive Designs and Effectiveness Designs and new sections on Comparative Effectiveness Research and Pragmatic Trials. Chapter 6 includes new material on Phase 0 Trials, expanded coverage of Futility Trials, a discussion of Medical Device approval, Off Label Drug use and the role of the FDA in regulating advertising. Additional new information includes the role of pill color and shape in association with the placebo effect and an examination of issues surrounding minority recruitment. The final chapter offers a new section on manuscript preparation along with a discussion of various guidelines being adopted by journals: CONSORT, STROBE, PRISMA, MOOSE and others; and coverage of Conflicts of Interest, Authorship, Coercive Citation, and Disclosures in Industry-Related Associations.

Building on the strengths of its predecessor in its comprehensive approach and authoritative advice, the new edition offers more of what has made this book a popular, trusted resource for students and working researchers alike.

The use of computational methods in statistics to face complex problems and highly dimensional data, as well as the widespread availability of computer technology, is no news. The range of applications, instead, is unprecedented. As often occurs, new and complex data types require new strategies, demanding for the development of novel statistical methods and suggesting stimulating mathematical problems. This book is addressed to researchers working at the forefront of the statistical analysis of complex systems and using computationally intensive statistical methods.

This interdisciplinary thesis introduces a systems biology approach to study the cell fate decision mediated by autophagy. A mathematical model of interaction between Autophagy and Apoptosis in mammalian cells is proposed. In this dynamic model autophagy acts as a gradual response to stress (Rheostat) that delays the initiation of bistable switch of apoptosis to give the cells an opportunity to survive. The author shows that his dynamical model is consistent with existing quantitative measurements of time courses of autophagic responses to cisplatin treatment. To understand the function of this response in cancer cells, he has provided a systems biology experimental framework to study quantitative and dynamical aspects of autophagy in single cancer cells using live-cell imaging and quantitative fluorescence microscopy. This framework can provide new insights on function of autophagic response in cancer cells.

Together, the volumes in this series present all of the data needed at various length scales for a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to, and remove carbon dioxide from, the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to nano- and microscopic events in a corrector scheme of regulated mechanism. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems, together with the mathematical tools to describe their functioning in quantitative terms. The present volume focuses on macroscopic aspects of the cardiovascular and respiratory systems in normal conditions, i.e., anatomy and physiology, as well as the acquisition and processing of medical images and physiological signals. * Reviews the anatomy and physiology of blood circulation and the body's ventilation * Reviews biological data for a better understanding of macroscopic scale processes * Describes the signals and images that are used to explore system function and as input data for computations

This is the first book entirely dedicated to Intravital Microscopy. It provides the reader with a broad overview of the main applications of Intravital Microscopy in various areas of the biomedical field. The book contains accurate descriptions of the state of the art methodologies used to image various organs at different level of resolution, ranging from whole tissue down to sub-cellular structures. Moreover, it is an extremely valuable guide to scientists that want to adopt this powerful technique and do not have experience with animal models and microscopy.

Life is produced by the interplay of water and biomolecules. This book deals with the physicochemical aspects of such life phenomena produced by water and biomolecules, and addresses topics including "Protein Dynamics and Functions," "Protein and DNA Folding," and "Protein Amyloidosis." All sections have been written by internationally recognized front-line researchers. The idea for this book was born at the 5th International Symposium "Water and Biomolecules," held in Nara city, Japan, in 2008. Written for: Scientists, academic libraries, advanced students

This volume presents a compelling collection of state-of-the-art work in algorithmic computational biology, honoring the legacy of Professor Bernard M.E. Moret in this field. Reflecting the wide-ranging influences of Prof. Moret's research, the coverage encompasses such areas as phylogenetic tree and network estimation, genome rearrangements, cancer phylogeny, species trees, divide-and-conquer strategies, and integer linear programming. Each self-contained chapter provides an introduction to a cutting-edge problem of particular computational and mathematical interest. Topics and features: addresses the challenges in developing accurate and efficient software for the NP-hard maximum likelihood phylogeny estimation problem; describes the inference of species trees, covering strategies to scale phylogeny estimation methods to large datasets, and the construction of taxonomic supertrees; discusses the inference of ultrametric distances from additive distance matrices, and the inference of ancestral genomes under genome rearrangement events; reviews different techniques for inferring evolutionary histories in cancer, from the use of chromosomal rearrangements to tumor phylogenetics approaches; examines problems in phylogenetic networks, including questions relating to discrete mathematics, and issues of statistical estimation; highlights how evolution can provide a framework within which to understand comparative and functional genomics; provides an introduction to Integer Linear Programming and its use in computational biology, including its use for solving the Traveling Salesman Problem. Offering an invaluable source of insights for computer scientists, applied mathematicians, and statisticians, this illuminating volume will also prove useful for graduate courses on computational biology and bioinformatics.

The model-based investigation of motions of anthropomorphic systems is an important interdisciplinary research topic involving specialists from many fields such as Robotics, Biomechanics, Physiology, Orthopedics, Psychology, Neurosciences, Sports, Computer Graphics and Applied Mathematics. This book presents a study of basic locomotion forms such as walking and running is of particular interest due to the high demand on dynamic coordination, actuator efficiency and balance control. Mathematical models and numerical simulation and optimization techniques are explained, in combination with experimental data, which can help to better understand the basic underlying mechanisms of these motions and to improve them. Example topics treated in this book are * Modeling techniques for anthropomorphic bipedal walking systems * Optimized walking motions for different objective functions * Identification of objective functions from measurements * Simulation and optimization approaches for humanoid robots * Biologically inspired control algorithms for bipedal walking * Generation and deformation of natural walking in computer graphics * Imitation of human motions on humanoids * Emotional body language during walking * Simulation of biologically inspired actuators for bipedal walking machines * Modeling and simulation techniques for the development of prostheses * Functional electrical stimulation of walking.

The creation and consumption of content, especially visual content, is ingrained into our modern world. This book contains a collection of texts centered on the evaluation of image retrieval systems. To enable reproducible evaluation we must create standardized benchmarks and evaluation methodologies. The individual chapters in this book highlight major issues and challenges in evaluating image retrieval systems and describe various initiatives that provide researchers with the necessary evaluation resources. In particular they describe activities within ImageCLEF, an initiative to evaluate cross-language image retrieval systems which has been running as part of the Cross Language Evaluation Forum (CLEF) since 2003.

To this end, the editors collected contributions from a range of people: those involved directly with ImageCLEF, such as the organizers of specific image retrieval or annotation tasks; participants who have developed techniques to tackle the challenges set forth by the organizers; and people from industry and academia involved with image retrieval and evaluation generally.

Mostly written for researchers in academia and industry, the book stresses the importance of combing textual and visual information - a multimodal approach - for effective retrieval. It provides the reader with clear ideas about information retrieval and its evaluation in contexts and domains such as healthcare, robot vision, press photography, and the Web.

This book develops methods using mathematical kinetic theory to describe the evolution of several socio-biological systems. Specifically, the authors deal with modeling and simulations of biological systems constituted by large populations of interacting cells, whose dynamics follow the rules of mechanics as well as their own ability to organize movement and biological functions. It proposes a new biological model focused on the analysis of competition between cells of an aggressive host and cells of the immune system. Modeling in kinetic theory may represent a way to understand phenomena of non equilibrium statistical mechanics that is not described by the traditional macroscopic approach. The authors of this work focus on models that refer to the Boltzmann equation (generalized Boltzmann models) with the dynamics of populations of several interacting individuals (kinetic population models). The book follows the classical research line applied to modeling real systems, linking the phenomenological observation of systems to modeling and simulations. used to identify the prediction ability of specific models. The book will be a valuable resource for applied mathematicians as well as researchers in the field of biological sciences. It may also be used for advanced graduate courses in biological systems modeling with applications to collective social behavior, immunology, and epidemiology.

Chemical processes in many fields of science and technology, including combustion, atmospheric chemistry, environmental modelling, process engineering, and systems biology, can be described by detailed reaction mechanisms consisting of numerous reaction steps. This book describes methods for the analysis of reaction mechanisms that are applicable in all these fields. Topics addressed include: how sensitivity and uncertainty analyses allow the calculation of the overall uncertainty of simulation results and the identification of the most important input parameters, the ways in which mechanisms can be reduced without losing important kinetic and dynamic detail, and the application of reduced models for more accurate engineering optimizations. This monograph is invaluable for researchers and engineers dealing with detailed reaction mechanisms, but is also useful for graduate students of related courses in chemistry, mechanical engineering, energy and environmental science and biology.

These proceedings from the 37th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering (MaxEnt 2017), held in Sao Carlos, Brazil, aim to expand the available research on Bayesian methods and promote their application in the scientific community. They gather research from scholars in many different fields who use inductive statistics methods and focus on the foundations of the Bayesian paradigm, their comparison to objectivistic or frequentist statistics counterparts, and their appropriate applications. Interest in the foundations of inductive statistics has been growing with the increasing availability of Bayesian methodological alternatives, and scientists now face much more difficult choices in finding the optimal methods to apply to their problems. By carefully examining and discussing the relevant foundations, the scientific community can avoid applying Bayesian methods on a merely ad hoc basis. For over 35 years, the MaxEnt workshops have explored the use of Bayesian and Maximum Entropy methods in scientific and engineering application contexts. The workshops welcome contributions on all aspects of probabilistic inference, including novel techniques and applications, and work that sheds new light on the foundations of inference. Areas of application in these workshops include astronomy and astrophysics, chemistry, communications theory, cosmology, climate studies, earth science, fluid mechanics, genetics, geophysics, machine learning, materials science, medical imaging, nanoscience, source separation, thermodynamics (equilibrium and non-equilibrium), particle physics, plasma physics, quantum mechanics, robotics, and the social sciences. Bayesian computational techniques such as Markov chain Monte Carlo sampling are also regular topics, as are approximate inferential methods. Foundational issues involving probability theory and information theory, as well as novel applications of inference to illuminate the foundations of physical theories, are also of keen interest.

The best way to become acquainted with a subject is to write a book about it. BenjaminDisraeli Cryobiologyisatruemultidisciplinaryscienceinvolvingconceptsfrombiology, medicine, and physics. Its ?eld comprises the study of any biologicalobject or system (e. g. , proteins, cells, tissues, organs, or organisms) under the temp- atures below the normal (ranging from hypothermic conditions to cryogenic temperatures): cold-adaptation of organisms; cryoconservation of biological objects; conservation of organs under hypothermic conditions; lyophilization; cryosurgery. Origins of cryobiology could be traced down to ancient Eg- tians; probably the ?rst scienti?c account of this science is the monograph by Sir Robert Boyle "New Experiments and Observations Touching Cold" (London, 1683). Twentieth century witnessed a rapid development of cryo- ologyrelatedtotheprogressofthecryogenicequipment(closedsystemsbased on liquid nitrogen, Joule-Tohomson cooling with mixed gases, etc. ), devel- ments of monitoring techniques, extension of the list of diseases that have been successfully treated by cryomedicine, and consolidation of research by foundation (simultaneously in 1964) of two major scienti?c societies in this ? eld - The Society for Cryobiology and The Society for Low Temperature Biology. There are a lot of good books on cryobiologythat can be divided into two groups: (1) the ones that treat the whole ?eld of cryobiology - these ones are somewhatout-of-dateand(2)thebooksonspeci?capplicationsofcryobiology such as cryosurgery or cryoconservation.

This review series covers trends in modern biotechnology, including all aspects of this interdisciplinary technology, requiring knowledge, methods, and expertise from chemistry, biochemistry, microbiology, genetics, chemical engineering and computer science.

In "Emergence, Mind, and Consciousness," author Gary A. Lucas does something that many consider impossible: he bridges the gap between a bottom-up description of brain mechanisms and the top-down emergence of mental processes. The result is a comprehensive yet readily understandable explanation of how consciousness emerges.

Lucas, however, strives to do more. He seeks to design an artificial agent with all the essential properties of the human mind- consciousness, declarative memory, a sense of self, reasoning skills, language, and social identity. His account is mechanistic, and yet, as the bio-inspired networks are linked to emergent mental properties, we come to understand that we can truly construct a conscious agent. We have a model for how to build one.

If you're interested in the emergent properties of mind, consciousness, cognition, self-awareness, social belongingness, or the possibility of constructing a robotic agent with such properties, then this is essential reading. It is conscious mind explained on a level that even a robot will understand it.

An ideal text for the natural product scientist looking for new techniques in research, this volume comprises the latest information on natural/plant resources.The comprehensive chapters cover the chemistry and pharmacology of a range of natural products - from Chinese herbal medicine to tea extracts, microbes to marine sponges, and the latest technologies to enhance the synthesis, isolation and purification of bioactive herbal compounds from these products. Adding additional value to the book are chapters on new tools in information technology that can greatly facilitate the research of natural product scientists, and the technologies available for evaluating medicinal herbal products for purity.

From the groundbreaking partnership of Macmillan Learning and Scientific American comes this one-of-a-kind introduction to the science of biology and its impact on the way we live. Available for the first time with Macmillan's new online learning tool, Achieve, Biology for a Changing World explores the core ideas of biology through chapters written and illustrated in the style of a Scientific American article. Chapters don't just feature compelling stories of real people-each chapter is a newsworthy story that serves as a context for covering the standard curriculum for the non-majors biology course. Achieve is Macmillan's new online learning platform that supports educators and students throughout the full range of instruction, including assets suitable for pre-class preparation, in-class active learning, and post-class study and assessment. The pairing of a powerful new platform with outstanding biology content provides an unrivaled learning experience.

This book presents recent methods for Systems Genetics (SG) data analysis, applying them to a suite of simulated SG benchmark datasets. Each of the chapter authors received the same datasets to evaluate the performance of their method to better understand which algorithms are most useful for obtaining reliable models from SG datasets. The knowledge gained from this benchmarking study will ultimately allow these algorithms to be used with confidence for SG studies e.g. of complex human diseases or food crop improvement. The book is primarily intended for researchers with a background in the life sciences, not for computer scientists or statisticians.

The convergence of biology and computer science was initially motivated by the need to organize and process a growing number of biological observations resulting from rapid advances in experimental techniques. Today, however, close collaboration between biologists, biochemists, medical researchers, and computer scientists has also generated remarkable benefits for the field of computer science. Systemic Approaches in Bioinformatics and Computational Systems Biology: Recent Advances presents new techniques that have resulted from the application of computer science methods to the organization and interpretation of biological data. The book covers three subject areas: bioinformatics, computational biology, and computational systems biology. It focuses on recent, systemic approaches in computer science and mathematics that have been used to model, simulate, and more generally, experiment with biological phenomena at any scale.

The emerging, multi-disciplinary field of systems biology is devoted to the study of the relationships between various parts of a biological system, and computer modeling plays a vital role in the drive to understand the processes of life from an holistic viewpoint. Advancements in experimental technologies in biology and medicine have generated an enormous amount of biological data on the dependencies and interactions of many different molecular cell processes, fueling the development of numerous computational methods for exploring this data. The mathematical formalism of Petri net theory is able to encompass many of these techniques. This essential text/reference presents a comprehensive overview of cutting-edge research in applications of Petri nets in systems biology, with contributions from an international selection of experts. Those unfamiliar with the field are also provided with a general introduction to systems biology, the foundations of biochemistry, and the basics of Petri net theory. Further chapters address Petri net modeling techniques for building and analyzing biological models, as well as network prediction approaches, before reviewing the applications to networks of different biological classification. Topics and features: investigates the modular, qualitative modeling of regulatory networks using Petri nets, and examines an Hybrid Functional Petri net simulation case study; contains a glossary of the concepts and notation used in the book, in addition to exercises at the end of each chapter; covers the topological analysis of metabolic and regulatory networks, the analysis of models of signaling networks, and the prediction of network structure; provides a biological case study on the conversion of logical networks into Petri nets; discusses discrete modeling, stochastic modeling, fuzzy modeling, dynamic pathway modeling, genetic regulatory network modeling, and quantitative analysis techniques; includes a Foreword by Professor Jens Reich, Professor of Bioinformatics at Humboldt University and Max Delbruck Center for Molecular Medicine in Berlin. This unique guide to the modeling of biochemical systems using Petri net concepts will be of real utility to researchers and students of computational biology, systems biology, bioinformatics, computer science, and biochemistry."

The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. Volume 5 is devoted to cells, tissues, and organs of the cardiovascular and ventilatory systems with an emphasis on mechanotransduction-based regulation of flow. The blood vessel wall is a living tissue that quickly reacts to loads applied on it by the flowing blood. In any segment of a blood vessel, the endothelial and smooth muscle cells can sense unusual time variations in small-magnitude wall shear stress and large-amplitude wall stretch generated by abnormal hemodynamic stresses. These cells respond with a short-time scale (from seconds to hours) to adapt the vessel caliber. Since such adaptive cell activities can be described using mathematical models, a key objective of this volume is to identify the mesoscopic agents and nanoscopic mediators required to derive adequate mathematical models. The resulting biomathematical models and corresponding simulation software can be incorporated into platforms developed in virtual physiology for improved understanding and training.

The book is organized so as to address in separate sections first the preparatory topics of medicine (clinical and epidemiological), science in general, and statistics (mathematical); then topics of epidemiological research proper; and, finally, topics of 'meta-epidemiological' clinical research. In those two main sections, a further grouping is based on the distraction between objects and methods of study. In this framework, the particular topics are addressed both descriptively and quasi-prescriptively, commonly with a number of explicatory annotations. This book is intended to serve as a handbook for whomever is, in whatever way, concerned with epidemiological or 'meta-epidemiological' clinical research. But besides this, it is also intended to serve as a textbook for students in introductory courses on 'epidemiological' research - to which end there is a suggested hierarchy of the concepts that might reasonably be covered.

Robert Rosen was not only a biologist, he was also a brilliant mathematician whose extraordinary contributions to theoretical biology were tremendous. Founding, with this book, the area of Anticipatory Systems Theory is a remarkable outcome of his work in theoretical biology. This second edition of his book Anticipatory Systems, has been carefully revised and edited, and includes an Introduction by Judith Rosen. It has also been expanded with a set of Prolegomena by Dr. Mihai Nadin, who offers an historical survey of this fast growing field since the original work was published. There is also some exciting new work, in the form of an additional chapter on the Ontology of Anticipation, by Dr. John Kineman. An addendum-- with autobiographical reminiscences by Robert Rosen, himself, and a short story by Judith Rosen about her father-- adds a personal touch. This work, now available again, serves as the guiding foundations for the growing field of Anticipatory Systems and, indeed, any area of science that deals with living organisms in some way, including the study of Life and Mind. It will also be of interest to graduate students and researchers in the field of Systems Science.

This treasure of popular science by the Russian biophysicist Mikhail V. Volkenstein is at last, more than twenty years after its appearance in Russian, available in English translation.

As its title Entropy and Information suggests, the book deals with the thermodynamical concept of entropy and its interpretation in terms of information theory. The author shows how entropy is not to be considered a mere shadow of the central physical concept of energy, but more appropriately as a leading player in all of the major natural processes: physical, chemical, biological, evolutionary, and even cultural.

The theory of entropy is thoroughly developed from its beginnings in the foundational work of Sadi Carnot and Clausius in the context of heat engines, including expositions of much of the necessary physics and mathematics, and illustrations from everyday life of the importance of entropy.

The author then turns to Boltzmann's epoch-making formula relating the entropy of a system directly to the degree of disorder of the system, and to statistical physics as created by Boltzmann and Maxwell---and here again the necessary elements of probability and statistics are expounded. It is shown, in particular, that the temperature of an object is essentially just a measure of the mean square speed of its molecules.

Fluctuations" in a system are introduced and used to explain why the sky is blue, and how, perhaps, the universe came to be so ordered. Whether statistical physics reduces ultimately to pure mechanics, as Laplace's demon" would have it, is also discussed.

The final three chapters concentrate on open systems, that is, systems which exchange energy or matter with their surroundings---first linear systems close to equilibrium, and then non-linear systems far from equilibrium. Here entropy, as it figures in the theory of such systems developed by Prigogine and others, affords explanations of the mechanism of division of cells, the process of aging in organisms, and periodic chemical reactions, among other phenomena.

Finally, information theory is developed---again from first principles---and the entropy of a system characterized as absence of information about the system. In the final chapter, perhaps the piece de resistance of the work, the author examines the thermodynamics of living organisms in the context of biological evolution. Here the value of biological information" is discussed, linked to the concepts of complexity and irreplaceability. The chapter culminates in a fascinating discussion of the significance of these concepts, all centered on entropy, for human culture, with many references to particular writers and artists.

The book is recommended reading for all interested in physics, information theory, chemistry, biology, as well as literature and art."

The present volume advances a recent historiographical turn towards the intersection of early modern philosophy and the life sciences by bringing together many of its leading scholars to present the contributions of important but often neglected figures, such as Ralph Cudworth, Nehemiah Grew, Francis Glisson, Hieronymus Fabricius ab Aquapendente, Georg Ernst Stahl, Juan Gallego de la Serna, Nicholas Hartsoeker, Henry More, as well as more familiar figures such as Descartes, Spinoza, Leibniz, Malebranche, and Kant. The contributions to this volume are organized in accordance with the particular problems that living beings and living nature posed for early modern philosophy: the problem of life in general, whether it constitutes something ontologically distinct at all, or whether it can ultimately be exhaustively comprehended "in the same manner as the rest "; the problem of the structure of living beings, by which we understand not just bare anatomy but also physiological processes such as irritability, motion, digestion, and so on; the problem of generation, which might be included alongside digestion and other vital processes, were it not for the fact that it presented such an exceptional riddle to philosophers since antiquity, namely, the riddle of coming-into-being out of - apparent or real - non-being; and, finally, the problem of natural order.