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 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.

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.

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.

This book presents cutting-edge papers and perspectives on the transport of oxygen to tissues by scientists in a multitude of disciplines such as biochemistry, engineering, mathematics, medicine, physics, physiology, veterinary and complementary medicine. The book is composed of the following 6 parts: Brain Oxygenation and Function, Tumor Oxygenation and Metabolism, Muscle Oxygenation and Sports Medicine, Cell Metabolism and Tissue Oxygenation, Methodology of O2 Measurements, and Special Topics. The articles in this book have been presented at the 42nd annual meeting of the International Society on Oxygen Transport to Tissue (ISOTT 2019) held in Albuquerque, New Mexico, USA, from July 28 to July 31, 2019. Academics, clinical and industry researchers, engineers, as well as graduate students who are interested in oxygen transport to tissue will find this book a great reference and a useful learning resource.

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.

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.

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.

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.

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.

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.

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 book outlines comprehensively the main medical uses of aptamers, from diagnosis to therapeutics in fourteen chapters. Pioneering topics covered include aptamer pharmaceuticals, aptamers for malign tumors, aptamers for personalized therapeutics and aptamers for point-of-care testing. The book offers an essential guide for medical scientists interested in developing aptamer-based schemes for better theranostics. It is therefore of interest for not only academic researchers, but also practitioners and medical researchers in various fields of medical science, medical research and bio-analytical chemistry.

It is now well known that proteases are found everywhere, in viruses and bacteria as well as in all human, animal and plant cells, and play a role in a variety of biological functions ranging from digestion, fertilization, development to senescence and death. Under physiological conditions the ability of proteases is regulated by endogenous inhibitors. However, when the activity of proteases is not regulated appropriately, disease processes can result, as seen in Alzheimer s disease, cancer metastasis and tumor progression, inflammation and atherosclerosis. Thus it is evident that there is an absolute need for a tighter control of proteolytic activities in different cells and tissues.

Aimed at graduate students and researchers with an interest in cellular proteolytic events, "Role of Proteases in Cellular Dysfunctions" is the second book on Proteases in this series. The book consists of three parts in specified topics based on current literatures for a better understanding for the readers with respect to their subject-wise interests. The first section of this book covers a brief idea about the neuronal disorders and the involvement of proteases such as calpains, caspases and matrix metalloproteases (MMPs). The second section covers the deadly disease cancer and its relation to ubiquitin-proteasome system, MMPs and serine proteases. The last section is about the role of proteases such as calpains, MMPs and serine protease as well as urokinase type plasminogen activator receptor (uPAR) in causing cardiovascular defects. "

This book addresses the background and significance of the factors potentially influencing the clinical and biological outcomes of metal-on-metal hip implants.Metal-on-metal bearings were introduced and evaluated as an alternative to other bearing couples, particularly metal-on-polyethylene, due to their enhanced wear resistance as determined in laboratory testing.Initially, reports of short-term clinical outcomes were favorable and an increasing number of metal-on-metal prostheses were implanted. Subsequently, isolated case findings describing adverse tissue responses around the articulation became the harbinger of an increasing number of reports describing pseudotumors and other significant lymphocytic-based responses associated with metal-on-metal prostheses. Questions have been raised as to whether this is an implant, design, or patient-specific response. The reasons why some patients have a negative biological response and pathology while others do not remain to be determined, but tens of thousands of patients in the US, the UK, and around the world are considered to be at risk. Leading researchers and clinicians describe the issues related to the nature of the biological and pathological responses and the protocols that should be followed to determine if an adverse response is occurring. This book is essential reading for researchers, engineers, and orthopaedic surgeons who are involved in the design, evaluation, and implantation of metal-on-metal prostheses."

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

The conquest of scurvy by James Cook during his three famous circumnavigations of 1768-1780 was a product of Cook's character, of his leadership, and of the wisdom of the naturalists who accompanied Cook; specialists who helped locate antiscorbutic plants during stopovers. In this book, Dr. Cuppage shows the importance of careful observation, and of controlled clinical trials. This is an account of the lasting medical effects of Cook's voyages as he tried to liberate mankind from the scourge of scurvy. Cuppage captures the sense of adventure that explorers and scientists share.

The book covers novel strategies of state of the art in engineering and clinical analysis and approaches for analyzing abdominal imaging, including lung, mediastinum, pleura, liver, kidney and gallbladder. In the last years the imaging techniques have experienced a tremendous improvement in the diagnosis and characterization of the pathologies that affect abdominal organs. In particular, the introduction of extremely fast CT scanners and high Magnetic field MR Systems allow imaging with an exquisite level of detail the anatomy and pathology of liver, kidney, pancreas, gallbladder as well as lung and mediastinum. Moreover, thanks to the development of powerful computer hardware and advanced mathematical algorithms the quantitative and automated\semi automated diagnosis of the pathology is becoming a reality. Medical image analysis plays an essential role in the medical imaging field, including computer-aided diagnosis, organ/lesion segmentation, image registration, and image-guided therapy. This book will cover all the imaging techniques, potential for applying such imaging clinically, and offer present and future applications as applied to the abdomen and thoracic imaging with the most world renowned scientists in these fields. The main aim of this book is to help advance scientific research within the broad field of abdominal imaging. This book focuses on major trends and challenges in this area, and it presents work aimed to identify new techniques and their use in medical imaging analysis for abdominal imaging.

This book addresses the pressing issues involved with the ethical conduct of research in one developing world region - the Arab Region. Clinical research has soared in the developing world -as pharmaceutical companies continue their search for regions with large, treatment naive populations - including the Arab region, and has profound implications for the health and the economies for the area. The ethical issues involved with the conduct of such research, however, have so far not been adequately addressed. This volume presents the issues regarding research ethics and research governance that have relevance for health authorities, regulators, industry, and academia. As a multi-authored volume it includes both international and local experts on ethical issues in research, representing all stakeholders, thus presenting a balanced view on this timely topic.

The whole field of drug research has become a minefield of sensitive issues with the opponents entrenched at opposite extremes taking pot shots at each other. The attacks made on drug research and the pharmaceutical industry in particular have become so venomous that an attempt needed to be made to provide a balanced ethical appraisal of the situation. Neither pro- nor antagonists are fully right, but some common grounds need to be found. The author believes that this commons grounds resides in the religious and philosophical foundations on which western industrial society has been built.