This book concerns the mathematical modeling and computer simulation of the human stomach. It follows the four modern P's (prevention, prediction, personalization, and precision in medicine) approach in addressing the highly heterogeneous nature of processes underlying gastric motility disorders manifested as gastroparesis, functional dyspepsia, myenteric enteropathy etc. The book comprehensively guides readers through the fundamental theoretical concepts to complex physiological models of the organ. This requires a deep and thorough understanding of driving pathophysiological mechanisms as well as the collaborative effort of specialists working in fundamental and biological science. Such a multidisciplinary partnership is vital because it upholds gnostic capabilities and provides the exchange of thoughts and ideas thus offering broad perspectives into the evolution and management of diseases. The book is a valuable resource for applied mathematicians, computational biologists, bioengineers, physicians, physiologists and researchers working in various fields of biomedicine.

This book contains the full papers presented at ICCEBS 2013 - the 1st International Conference on Computational and Experimental Biomedical Sciences, which was organized in Azores, in October 2013. The included papers present and discuss new trends in those fields, using several methods and techniques, including active shape models, constitutive models, isogeometric elements, genetic algorithms, level sets, material models, neural networks, optimization and the finite element method, in order to address more efficiently different and timely applications involving biofluids, computer simulation, computational biomechanics, image based diagnosis, image processing and analysis, image segmentation, image registration, scaffolds, simulation and surgical planning. The main audience for this book consists of researchers, Ph.D students and graduate students with multidisciplinary interests related to the areas of artificial intelligence, bioengineering, biology, biomechanics, computational fluid dynamics, computational mechanics, computational vision, histology, human motion, imagiology, applied mathematics, medical image, medicine, orthopaedics, rehabilitation, speech production and tissue engineering.

This book addresses the most important aspects of how to plan and evaluate clinical trials with a composite primary endpoint to guarantee a clinically meaningful and valid interpretation of the results. Composite endpoints are often used as primary efficacy variables for clinical trials, particularly in the fields of oncology and cardiology. These endpoints combine several variables of interest within a single composite measure, and as a result, all variables that are of major clinical relevance can be considered in the primary analysis without the need to adjust for multiplicity. Moreover, composite endpoints are intended to increase the size of the expected effects thus making clinical trials more powerful. The book offers practical advice for statisticians and medical experts involved in the planning and analysis of clinical trials. For readers who are mainly interested in the application of the methods, all the approaches are illustrated with real-world clinical trial examples, and the software codes required for fast and easy implementation are provided. The book also discusses all the methods in the context of relevant guidelines related to the topic. To benefit most from the book, readers should be familiar with the principles of clinical trials and basic statistical methods.

This book shares the latest research and practice-oriented findings in medical sciences with a wide audience. It addresses a range of contemporary issues, often unresolved or contentious, across various medical fields, including advances in the management of hemorrhagic brain stroke. It also discusses metastatic renal cell carcinoma - a global scourge with an extremely poor long-term survival prognosis, the course and sequelae of renal cell carcinoma, as well as advances in targeted molecular therapy with sunitinib, a receptor tyrosine kinase inhibitor. Further, it examines the molecular targeting of proliferative signaling of the epidermal growth factor receptor in the first-line treatment of patients with metastatic non-small-cell lung cancer. Other articles cover clearance of toxins in hemodialyzed patients; the search for diagnostic and therapeutic markers in the connective tissue disease scleroderma; obesity linked to inappropriate dietary habit; clinical problems related to the diagnosis of sensitization to fungi and its role in asthma; and reasons for the perilous trend of avoiding basic vaccinations in children. Lastly, the book explores the rapid developments in e-health technologies that increase access to health services, particularly for the elderly. The book is intended for clinical specialists, researchers, and all allied health professionals from various fields.

Founded in 1959, the series has moved from its initial focus on medicinal chemistry to a much wider scope. This volume encompasses all fields concerned with the development of therapeutic drugs, and the elucidation of their mechanisms of action. When combined with the other volumes, it serves as a time-saving source of information for researchers concerned with drug research, and all those who need to keep abreast of ongoing developments in medicines.

This book brings together the voices of leading experts in the frontiers of biostatistics, biomedicine, and the health sciences to discuss the statistical procedures, useful methods, and novel applications in biostatistics research. It also includes discussions of potential future directions of biomedicine and new statistical developments for health research, with the intent of stimulating research and fostering the interactions of scholars across health research related disciplines. Topics covered include: Health data analysis and applications to EHR data Clinical trials, FDR, and applications in health science Big network analytics and its applications in GWAS Survival analysis and functional data analysis Graphical modelling in genomic studies The book will be valuable to data scientists and statisticians who are working in biomedicine and health, other practitioners in the health sciences, and graduate students and researchers in biostatistics and health.

This book advocates the importance and value of errors for the progress of scientific research! Hans Kricheldorf explains that most of the great scientific achievements are based on an iterative process (an 'innate self-healing mechanism'): errors are committed, being checked over and over again, through which finally new findings and knowledge can arise. New ideas are often first confronted with refusal. This is so not only in real life, but also in scientific and medical research. The author outlines in this book how great ideas had to ripen over time before winning recognition and being accepted. The book showcases in an entertaining way, but without schadenfreude, that even some of the most famous discoverers may appear in completely different light, when regarding errors they have committed in their work. This book is divided into two parts. The first part creates a fundament for the discussion and understanding by introducing important concepts, terms and definitions, such as (natural) sciences and scientific research, laws of nature, paradigm shift, and progress (in science). It compares natural sciences with other scientific disciplines, such as historical research or sociology, and examines the question if scientific research can generate knowledge of permanent validity. The second part contains a collection of famous fallacies and errors from medicine, biology, chemistry, physics and geology, and how they were corrected. Readers will be astonished and intrigued what meanders had to be explored in some cases before scientists realized facts, which are today's standard and state-of-the-art of science and technology. This is an entertaining and amusing, but also highly informative book not only for scientists and specialists, but for everybody interested in science, research, their progress, and their history!

This volume explores experimental approaches used to study Duchenne muscular dystrophy (DMD), an X-linked degenerative skeletal muscle disease caused by mutations in the dystrophin gene. Including the latest progress and scientific achievements, the book covers recent discoveries achieved through in vivo gene editing which have proven to be promising in restoring dystrophin expression, at least in ameliorating skeletal muscle symptoms, and the contents focus on "Omics" techniques in gene expression, protein expression, miRNAs, and long non-coding RNA analysis, as well as experimental studies of the structural/functional changes affecting the skeletal and cardiac muscles and ongoing preclinical studies and clinical trials. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Duchenne Muscular Dystrophy: Methods and Protocols serves as a guide for researchers exploring the complicated nature of dystrophin in the hope of helping the victims of this disorder.

This edited volume is a definitive text on adaptive clinical trial designs from creation and customization to utilization. As this book covers the full spectrum of topics involved in the adaptive designs arena, it will serve as a valuable reference for researchers working in industry, government and academia. The target audience is anyone involved in the planning and execution of clinical trials, in particular, statisticians, clinicians, pharmacometricians, clinical operation specialists, drug supply managers, and infrastructure providers. In spite of the increased efficiency of adaptive trials in saving costs and time, ultimately getting drugs to patients sooner, their adoption in clinical development is still relatively low. One of the chief reasons is the higher complexity of adaptive design trials as compared to traditional trials. Barriers to the use of clinical trials with adaptive features include the concerns about the integrity of study design and conduct, the risk of regulatory non-acceptance, the need for an advanced infrastructure for complex randomization and clinical supply scenarios, change management for process and behavior modifications, extensive resource requirements for the planning and design of adaptive trials and the potential to relegate key decision makings to outside entities. There have been limited publications that address these practical considerations and recommend best practices and solutions. This book fills this publication gap, providing guidance on practical considerations for adaptive trial design and implementation. The book comprises three parts: Part I focuses on practical considerations from a design perspective, whereas Part II delineates practical considerations related to the implementation of adaptive trials. Putting it all together, Part III presents four illustrative case studies ranging from description and discussion of specific adaptive trial design considerations to the logistic and regulatory issues faced in trial implementation.

Bringing together the expertise of leading key opinion leaders from pharmaceutical industry, academia, and regulatory agencies, this book provides a balanced and comprehensive coverage of practical considerations for adaptive trial design and implementation.

This volume is a unique combination of papers that cover critical topics in biostatistics from academic, government, and industry perspectives. The 6 sections cover Bayesian methods in biomedical research; Diagnostic medicine and classification; Innovative Clinical Trials Design; Modelling and Data Analysis; Personalized Medicine; and Statistical Genomics. The real world applications are in clinical trials, diagnostic medicine and genetics. The peer-reviewed contributions were solicited and selected from some 400 presentations at the annual meeting of the International Chinese Statistical Association (ICSA), held with the International Society for Biopharmaceutical Statistics (ISBS). The conference was held in Bethesda in June 2013, and the material has been subsequently edited and expanded to cover the most recent developments.

This edited work presents studies that clarify the basics of producing recombinant enzymes that finally lead to commercialization. It enables researchers to see what is crucial to the commercialization process, from examining the cloning method, using analytical techniques such as calculating the total protein content and enzyme activity, through considering upstream and downstream processes, to the final product. Readers will discover the importance of the cloning method as it influences the upstream and downstream processes and determines the level of success of the recombinant enzyme commercialization processes. We see that the two main factors that are particularly sensitive during the cloning process are the vector and the host. A discussion of analytical techniques is presented followed by studies on important stages during the upstream processes including the process of optimizing the media to get results and high enzyme activity. Downstream processes such as the cell disruption technique, purification and formulation of the final product are then considered. The reader is introduced to software that helps streamline recombinant enzyme production from the upstream to downstream processes, to facilitate the process of up-scaling production. This work includes a case study as tool, to guide understanding of the commercialization process. The work is written for researchers in the field and is especially suited to those who are under pressure to embark on the tough process of commercialization.

One.- 1 Characterization.- 2 Serum-Free Media.- 3 Differentiation Potential of Cancer Cells.- 4 Spheroids and Xenografts.- 5 Predictive Assays for Drug and Radiation Resistance.- Two.- 6 Colorectum.- 7 Testicular Germ Cell Tumours.- 8 Epidermis.- 9 Lung Cancer.- 10 Brain.- 11 Ovarian Tumours.- 12 Prostate.- 13 Breast Cancer.

Prescription drugs are a basic and invaluable part of society today, but there is debate surrounding the methods of testing new drugs, the possible misuse of prescription drugs, and the economics of drug production and use. This book examines the evolution of prescription drugs in the United States, as well as the formation of the pharmaceutical industry. It begins with a history of prescription drugs, dating back to their origins, then moves through the Industrial Revolution and into the present day. It also delves into the issues and controversies related to prescription drugs, such as drug costs, regulations, prescription drug abuse, insurance complications, and more. Both implemented and proposed solutions are also discussed. One of the most valuable aspects of the book is that it surveys the history of prescription drugs in a manner that helps the reader identify key issues in an easy-to-understand fashion. Finally, the perspectives chapter allows a broad range of voices to be heard, allowing crucial, diverse perspectives to round out the author's expertise. Provides readers with an understanding of the various types of drugs and how they differ in their effects and possible applications Introduces a detailed review of the steps involved in the preclinical, clinical, and post-clinical stages of testing of a new prescription drug Outlines some major issues in the way experimental drugs are tested, such as gender, age, and racial bias Reviews the current status of prescription drug abuse in the United States Explains issues involved in the pricing of prescription drugs and issues involved in over-pricing

The blood system is multi-scale, from the organism to the organs to cells to intracellular signaling pathways to macromolecule interactions. Blood consists of circulating cells, cellular fragments (platelets and microparticles), and plasma macromolecules. Blood cells and their fragments result from a highly-ordered process, hematopoiesis. Definitive hematopoiesis occurs in the bone marrow, where pluripotential stem cells give rise to multiple lineages of highly specialized cells. Highly-productive and continuously regenerative, hematopoiesis requires a microenvironment of mesenchymal cells and blood vessels. A Systems Biology Approach to Blood is divided into three main sections: basic components, physiological processes, and clinical applications. Using blood as a window, one can study health and disease through this unique tool box with reactive biological fluids that mirrors the prevailing hemodynamics of the vessel walls and the various blood cell types. Many blood diseases, rare and common can and have been exploited using systems biology approaches with successful results and therefore ideal models for systems medicine. More importantly, hematopoiesis offers one of the best studied systems with insight into stem cell biology, cellular interaction, development; linage programing and reprograming that are every day influenced by the most mature and understood regulatory networks.

This book is a treatise on cardiomyocytes, the most important cell for the contractile function of the heart. There has been significant progress in our understanding of the function-related structure, developmental processes and their determinants, mechanisms of cell cycle regulation, post-natal growth, energy metabolism, and reversible and irreversible response of cardiomyocytes to diverse forms of physiological stress and injury. There is also more clarity on the alterations in the biological mechanisms in cardiomyocytes that lead to pathological states and the changes in the cells that occur secondary to disease conditions. Thanks to these advances in knowledge, there have been great gains in attempts to identify disease biomarkers and therapeutic targets for better management of patients with heart diseases. Possibilities to induce regeneration or proliferation of cardiomyocytes and thus repair and or regenerate the damaged heart are also on the horizon.

At the age of eleven, Mark Greene nearly died. Neither he nor his parents knew that Mark suffered from end stage renal disease; he would need a kidney transplant to survive. Now, more than twenty-six years after his successful transplant operation, Greene tells the story of his survival following that operation.

Currently, there are approximately 170,000 organ transplant recipients in the United States, each with unique stories but sharing the commonality of improved quality of life. In "Life and Hope, " Greene discusses important principles that will not only contribute to the longevity of organ transplants, but also help recipients continue to improve their overall well-being. He blends personal experience and academic research to both teach and enlighten in a way that brings meaning to organ transplantation.

Greene shares a very personal story about his ordeal with a misdiagnosed illness that nearly took his life and nearly destroyed his family. His story is one of transformation, as he moves from the brink of death to a life full of meaning-a unique story and real-life experience that demonstrates how the organ transplant experience so eloquently contributes to the human experience.

Allergy is developing into one of the most prevalent diseases affecting individuals in the very early days of life. While the cause of this epidemic is still unclear, it appears that the westernized life style is playing an important role, which includes nutrition, possibly air pollution as well as hygienic conditions. While epidemiologic studies were able to narrow down these factors, basic research discovered novel mechanisms that control the organisms tolerance against allergens. Particularly interesting is the role of microorganisms that colonize or infect a host and thereby cause damage and immunological activation followed by sensitization or exacerbation of already existing sensitizations. However at the same time microbial activation of the immune system can help to generate a protective immunity that prevents allergen sensitization. The current book is collecting these evidences and connects epidemiologic and clinical mechanistic knowledge. Only the synthesis of this knowledge will help to find solutions to the ongoing allergy epidemic in terms of public health activities, prevention and therapy.

Over the last twenty years there has been a dramatic upsurge in the application of meta-analysis to medical research. This has mainly been due to greater emphasis on evidence-based medicine and the need for reliable summaries of the vast and expanding volume of clinical research. At the same time there have been great strides in the development and refinement of the associated statistical methodology. This book describes the planning, conduct and reporting of a meta-analysis as applied to a series of randomized controlled clinical trials.

• The various approaches are presented within a general unified framework.

• Meta-analysis techniques are described in detail, from their theoretical development through to practical implementation.

• Each topic discussed is supported by detailed worked examples.

• A comparison of fixed and random effects approaches is included, as well as a discussion of Bayesian methods and cumulative meta-analysis.

• Fully documented programs using standard statistical procedures in SAS are available on the Web.

Through case studies, theoretical research and interviews with leading players in science and governance, this book introduces a new understanding of change in governance of bioscience research. In particular it examines change as it is shaped by approaches developed by Science and Technology Studies and Sociology of Scientific Knowledge theorists.

MILS-13 provides an up-to-date review on the relationships between essential metals and human diseases, covering 13 metals and 3 metalloids: The bulk metals sodium, potassium, magnesium, and calcium, plus the trace elements manganese, iron, cobalt, copper, zinc, molybdenum, and selenium, all of which are essential for life. Also covered are chromium, vanadium, nickel, silicon, and arsenic, which have been proposed as being essential for humans in the 2nd half of the last century. However, if at all, they are needed only in ultra-trace amounts, and because of their prevalence in the environment, it has been difficult to prove whether or not they are required. In any case, all these elements are toxic in higher concentrations and therefore, transport and cellular concentrations of at least the essential ones, are tightly controlled; hence, their homeostasis and role for life, including deficiency or overload, and their links to illnesses, including cancer and neurological disorders, are thoroughly discussed. Indeed, it is an old wisdom that metals are indispensable for life. Therefore, Volume 13 provides in an authoritative and timely manner in 16 stimulating chapters, written by 29 internationally recognized experts from 7 nations, and supported by more than 2750 references, and over 20 tables and 80 illustrations, many in color, a most up-to-date view on the vibrant research area of the Interrelations between Essential Metal Ions and Human Diseases.

This book provides a clearly structured introduction to hydrogen biology and medicine. Hydrogen is the one of the most abundant elements in the universe and has the simplest structure. In 2007, Japanese researchers found that the selective oxidation of hydrogen has a therapeutic effect on various diseases and injuries, sparking widespread interest in the biomedical field. In recent years, hundreds of peer-reviewed papers have been published internationally reporting the positive effects of hydrogen on many human diseases, including strokes, diabetes, Parkinson's disease, Alzheimer's disease and sepsis. The authors provide readers with a comprehensive overview of this subject, from its physical and chemical properties to its biological effects, as well as the problems and obstacles that exist.

This book discusses the role of nutrients and vitamins in cancer prevention and treatment. Basic and clinical scientists from different regions of the world have contributed to this volume. The incidence of cancer is on the rise internationally and many of these cancers appear to be attributable to diet, lifestyle, and environmentally related factors. In recent years, many cancer causing substances and cancer protective agents which are associated with these factors have been identified and extensively tested in experimental models. This work also focuses on newer conceptual ideas that have emerged regarding the functions of nutrients on cellular and molecular levels.

This volume includes the information necessary to understand recent critical advances in the mechanisms of intestinal tumorigenesis and to comprehend the complexity of the process. The volume aims to entice new researchers to participate in relevant studies, and to provide a forum for discussion within the scientific community to shape future research in this field. Discoveries in intestinal tumorigenesis lead to further understanding of mechanisms involved in colon cancer. Additionally, advancements in techniques and methods open the doors for new approaches to better define the molecular and organismal mechanisms of intestinal tumorigenesis. Chapters are authored by widely published authorities in the field. Each year, there are close to 150,000 new cases of colorectal cancer, which results in approximately 50,000 deaths per year in the United States; these figures render colorectal cancer a significant health concern. Studies attempting to understand the mechanisms of development and progression of colorectal cancer have been ongoing for decades and each year brings new discoveries yielding a better comprehension of the underlying processes at work.

Pathophysiology and Analysis.- Lipid Peroxides and Related Radicals in Clinical Medicine.- Reactive Oxygen Species in Normal Physiology, Cell Injury and Phagocytosis.- Free Radical Mechanisms for Chromosomal Instability in Bloom's Syndrome.- The Analysis of Free Radicals, Lipid Peroxides, Antioxidant Enzymes and Compounds Related to Oxidative Stress as Applied to the Clinical Chemistry Laboratory.- Organ Specific Disorders.- Free Radicals and the Pathogenesis of Neuronal Death: Cooperative Role of Excitatory Amino Acids>.- Free Radicals and Ocular Disease.- Active Oxygen Mechanisms of UV Inflammation.- Oxygen-Free Radicals at Myocardial Level: Effects of Ischaemia and Reperfusion.- Mechanisms of Atherosclerosis: Role of LDL Oxidation.- Tissue Iron Overload and Mechanisms of Iron-Catalyzed Oxidative Injury.- Free Radicals in the Pathophysiology of Pulmonary Injury and Disease.- Lipid Peroxides in Hepatic, Gastrointestinal, and Pancreatic Diseases.- Reactive Oxygen Molecules in the Kidney.- Reactive Oxygen Species (ROS) and Reproduction.- Systemic Involvement.- Autoimmune and Inflammatory Diseases.- Antioxidants and Cancer: Molecular Mechanisms.- New Directions for Free Radical Cancer Research and Medical Applications.- Shock and Multiple Organ Failure.- Role of Nutrients in the Cause and Prevention of Oxygen Radical Pathology.- Involvement of Free Radical Mechanism in the Toxic Effects of Alcohol: Implications for Fetal Alcohol Syndrome.- Therapeutic Intervention.- 21-Aminosteroids ("Lazaroids").- The Potential of Gliclazide, a Sulphonylurea to Influence the Oxidative Processes within the Pathogenesis of Diabetic Vascular Disease.- Interactions between Vitamin E, Free Radicals, and Immunity During the Aging Process.- Vitamins and Carotenoids - A Promising Approach to Reducing the Risk of Coronary Heart Disease, Cancer and Eye Diseases.- Free Radical Scavenging and Antioxidant Activity of Plant Flavonoids.- Plasma Clearance and Immunologic Properties of Long-Acting Superoxide Dismutase Prepared Using 35,000 to 120,000 Dalton Poly-Ethylene Glycol.- Clinical Trials with Dismutec(TM) (Pegorgotein; Polyethylene Glycol-Conjugated Superoxide Dismutase; PEG-SOD) in the Treatment of Severe Closed Head Injury.- Poster Presentations.- A New Method for Detecting Lipid Peroxidation by Using Dye Sensitized Chemiluminescence.- Chemiluminescence and the Challenge to Attomole Detection.- Evidence Against Malondialdehyde Bound to Cellular Consituents in Phospholipid Peroxidation.- Evaluation of In Vivo Free Radical Activity During Endotoxic Schock Using Scavengers, Electron Microscopy, Spin Traps, and Electron Paramagnetic Spectroscopy.- Involvement of Hydroxyl Radicals in Endotoxin-Evoked Shock.- The Role of Nitric Oxide in Endotoxin-Elicited Hypodynamic Circulatory Failure.- In Vivo Evaluation of the Role of Neutrophil-Derived Free Radicals in the Development of Endotoxic Shock.- Photosensitized Formation of 8-Hydroxy-2'-Deoxyguanosine by A Cationic meso-Substituted Porphyrin.- Aging Associated Declines in the Antioxidant Enzymes of Human Testis.- Lipid Peroxidation in Normal Pregnancy and Preeclampsia.- Alkylation of Purine Bases By Carbon-Centered Radicals.- Cytochrome Biochemistry in Sheep Retina Following Exposure to Oxygen.- Cytochrome Oxidase Activity in the Fetal Sheep Retina.- Age-Related Phospholipid Hydroperoxide Levels in Gerbil Brain Measured by HPLC-Chemiluminescence Assay and Their Relation to Hydroxyl Radical Stress - Clinical Implications.- Lipid Peroxidation and Diabetic Complications: Effect of Antioxidant Vitamins C and E.- Vascular Complications of Patients in Kuwait with Type 2 Diabetes Mellitus (NIDDM) and Elevated Serum Lipid Peroxides.- Vascular and Cellular Protein Changes Precede Hippocampal Pyramidal Cell Loss Following Global Ischemia in the Rat.- Dietary Antioxidants and Breast Cancer Risk: Effect Modification by Family History.- Effect of MAK-4 and MAK-5 on Endothelial Cell- and Soyabean Lipoxygenase-Induced LDL Ox

This book offers a compilation of papers on the role of melanin-concentrating hormone (MCH) in sleep, sleep disorders and neuroendocrine functions. Leading experts in sleep medicine, psychiatry and neuroendocrinology provide a broad perspective on the field, from the anatomical structure and physiology of the MCH system to the connection with other systems influencing sleep and diseases like anxiety and depression. The potential of MCHR-1 antagonists as anxiolytic/antidepressant drugs is also reviewed. The book will represent an interdisciplinary guide for sleep disorder specialists, sleep researchers, psychiatrists, neurologists, psychologists, and behavioral sleep medicine specialists.