Adaptive Designs for Sequential Treatment Allocation presents a rigorous theoretical treatment of the results and mathematical foundation of adaptive design theory. The book focuses on designing sequential randomized experiments to compare two or more treatments incorporating information accrued along the way. The authors first introduce the terminology and statistical models most commonly used in comparative experiments. They then illustrate biased coin and urn designs that only take into account past treatment allocations as well as designs that use past data, such as sequential maximum likelihood and various types of doubly adaptive designs. The book also covers multipurpose adaptive experiments involving utilitarian choices and ethical issues. It ends with adaptive methods that include covariates in the design. The appendices present basic tools of optimal design theory and address Bayesian adaptive designs. This book helps readers fully understand the theoretical properties behind various adaptive designs. Readers are then equipped to choose the best design for their experiment.

This book is a self-contained introduction to Statistics, presented in the context of clinical trials and pharmaceutical drug development. It focuses on the statistical analyses most commonly used in drug development and is therefore an ideal introduction to pharmaceutical statistics. Instead of introducing a series of statistical techniques, the book's organizational structure follows the order in which numerical information and statistical analyses are used in trials and new drug development.All students taking classes in pharmaceutical sciences and clinical research need a solid knowledge and understanding of the nature, methods, application and importance of Statistics. They need to understand:why, and how data are collected in clinical trials; how these data are summarized and analyzed; what the results mean in the context of the clinical research question; and, how the results are communicated to regulatory agencies and to scientific and medical communities.This title therefore adopts a unique approach and concept in organization of the content. It begins with an introduction to statistical theory, analysis and interpretation. This is followed by a discussion of t-tests and confidence intervals. Readers are then taken through the whole process of new drug development (using one specific example throughout) that is meaningful in the context of their broader studies. Throughout this process, statistical techniques and analyses are introduced in the order in which they are employed during the process.The book's realistic scientific and progressive organization from pre-clinical trials to clinical pharmacology through clinical trials is novel, meaningful and educationally powerful. The book emphasises the importance of descriptive statistics as well as inferential statistics, something that is rarely done.Supplementary material is included for this text on the PharmPress website in the form of PowerPoint lecture notes on Statistics (based on content of this book) that can be downloaded by lecturers.

"Bioinformatics of Human Proteomics" discusses the development of methods, techniques and applications in the field of protein bioinformatics, an important direction in bioinformatics. It collects contributions from expert researchers in order to provide a practical guide to this complex field of study. The book covers the protein interaction network, drug discovery and development, the relationship between translational medicine and bioinformatics, and advances in proteomic methods, while also demonstrating important bioinformatics tools and methods available today for protein analysis, interpretation and predication. It is intended for experts or senior researchers in the fields of clinical research-related biostatistics, bioinformatics, computational biology, medicine, statistics, system biology, molecular diagnostics, biomarkers, or drug discovery and development. Dr.Xiangdong Wang works as a distinguished professor of Respiratory Medicine at Fudan University, Shanghai, China. He serves as Director of Biomedical Research Center, Fudan University Zhongshan Hospital and adjunct professor of Clinical Bioinformatics at Lund University, Sweden. His main research is focused on the role of clinical bioinformatics in the development of disease-specific biomarkers and dynamic network biomarkers, the molecular mechanism of organ dysfunction and potential therapies.

The health of the proteome depends upon protein quality control to regulate the proper synthesis, folding, translocation, and clearance of proteins. The cell is challenged constantly by environmental and physiological stress, aging, and the chronic expressions of disease associated misfolded proteins. Substantial evidence supports the hypothesis that the expression of damaged proteins initiates a cascade of molecular events that leads to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and other diseases of protein conformation.

Focusing on improving the diagnosis, prognosis, and management of human disease, this book takes on the issues of research design, measurement, and evaluation which are critical to clinical epidemiology. This second edition of Clinical Epidemiology: Practice and Methods opens with how best to frame a clinical research question, the ethics associated with doing a research project in humans, and the definition of various biases that occur in clinical research. From there, it continues by examining issues of design, measurement, and analysis associated with various research designs, including determination of risk in longitudinal studies, assessment of therapy in randomized controlled clinical trials, and evaluation of diagnostic tests, and then delves into the more specialized area of clinical genetic research, before concluding with basic methods used in evidence-based decision making including critical appraisal, aggregation of multiple studies using meta-analysis, health technology assessment, clinical practice guidelines, development of health policy, translational research, how to utilize administrative databases, and knowledge translation. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and practical advice to ensure real world success. Comprehensive and authoritative, Clinical Epidemiology: Practice and Methods, Second Edition is intended to educate researchers on how to undertake clinical research and should be helpful not only to medical practitioners but also to basic scientists who want to extend their work to humans, to allied health professionals interested in scientific evaluation, and to trainees in clinical epidemiology.

The subject of this book is stem cell research and regenerative medicine. Stem cells are undifferentiated cells that have the ability to differentiate into different lineages of the body. Stem cells carry tremendous potential for the treatment of a broad range of disease and injuries. Stem cells exist in embryonic, foetal, and adult tissues, including the adult central nervous system. This book aims at, in depth, the recent developments in stem cell research and regenerative medicine. Though this book encompasses all the fields of stem cell research and regenerative medicine, it emphasises embryonic and adult stem cells.

This volume is based on the Workshop on Systems Biology of Tumor Dormancy meeting, held July 25th to July 28th, 2011. The first annual CCSB workshop brought together biologists, clinicians, mathematicians, and computer scientists to discuss various aspects of tumor dormancy and develop novel mathematical/computational models with the keynote speakers. Specific topics included the angiogenic switch, immune system interactions, cancer stem cells and signaling.

Genes, which are carried on chromosomes, are the basic physical and functional units of heredity. Genes are specific sequences of bases that encode instructions on how to make proteins. Although genes get a lot of attention, it's the proteins that perform most life functions and even make up the majority of cellular structures. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is an experimental treatment that involves introducing genetic material into a person's cells to fight disease. Gene therapy is being studied in clinical trials for many different types of cancer and for numerous other diseases. This new book presents the latest research in the field from around the world.

Circadian rhythms are such an innate part of our lives that we rarely pause to speculate why they even exist. Some studies have suggested that the disruption of the circadian system may be causal for obesity and manifestations of Metabolic Syndrome (MetS). Shift-work, sleep-deprivation and bright-light-exposure at night are related to increased adiposity (obesity) and prevalence of MetS. It has been provided evidence of clock genes expression in human adipose tissue and demonstrated its association with different components of the MetS. Moreover, current studies are illustrating the particular role of different clock genes variants and their predicted haplotypes in MetS.

The purpose of Chronobiology and Obesity is to describe the mechanisms implicated in the interaction between chonodisruption and metabolic-related illnesses, such as obesity and MetS, with different approaches."

"Molecular Pharmacognosy" discusses the application of molecular biology in resource science and authentication of traditional Chinese medicine (TCM). This book reviews the latest developments in pharmacognosy, introduces a series of new views and insights, presents the hotspots and focus of the field of study on molecular pharmacognosy, and predicts a new direction of study on the resource science of TCM. Furthermore, the book also provides an open communications platform for the development of molecular pharmacognosy. This book is intended for biomedical scientists and researchers in the fields of molecular biology, traditional medicine and natural pharmaceutics.

Professor Lu-qi Huang is Director of the Collaborating Centre of the World Health Organization for Traditional Medicine (Chinese Materia Medica) and Vice-Chairman of the Australia Chinese Association for Biomedical Sciences Inc.

A vast number of diagnostic and therapeutic decisions are based on measuring blood concentrations of molecules, yet most biochemical and pharmacological events actually take place in the tissues. Microdialysis is a key semi-invasive sampling technique to measure in vivo drug penetration to the target site in humans, the method being feasible in virtually every organ. Authored by international experts in this cutting edge field, this book will provide a comprehensive overview of microdialysis and its application for measuring drug distribution in drug development.

Alzheimer's disease (AD), the most common form of neurodegenerative disorder in the elderly, is characterised pathologically by extracellular amyloid plaques and intracellular neurofibrillary tangles, pathophysiologically by synaptic dysfunction, and clinically by a progressive decline in cognition. Currently, AD has no cure and its prevalence is predicted to triple by 2050 with the rapid increase in the ageing population, unless more effective treatments are developed. Since the publication of the second book volume, the rapid progress in the research fields of AD and dementia continues through the intensive efforts of research scientists worldwide. This third book volume contains 15 chapters, bringing together a presentation of research frontiers in current AD/dementia research. The topics include molecular genetics of AD, gene expression abnormalities in AD progression, presenilins, taupathy in AD, single -induced(neuron gene expression abnormalities in AD, intracellular A neurodegeneration, roles of lipoprotein receptors in AD onset and progression, cholesterol and tau hyperphosphorylation, AD diagnostics and therapeutic strategies, in vivo visualisation of amyloid-like structures, cathepsin B, antiamyloidogenesis and neuroprotection, environmental enrichment, Fragile X mental retardation gene and dementia, category learning in Parkinson's disease, cerebrovascular disease and dementia, and dementia and hypertension. These chapters cover current advances in our understanding of the pathogenic mechanisms underlying AD and dementia, in the diagnosis of early AD and dementia, and in the development of therapeutic agents that target memory-relevant AD pathogenesis. The book will be highly valuable to students and scientists worldwide who are interested in the scientific research progress in AD and dementia.

The EuroQol Group first met in Rotterdam in May 1987 determined to develop a standardised non-disease-specific instrument for valuing health-related quality of life. The book traces the activities of the Group over the next 25 years. The instrument constructed, eventually named the EQ-5D, was translated into many languages and used in a wide range of countries and settings. The book describes how the instrument's descriptive system was determined, how translation and language issues were handled, and how valuations were provided. Recent developments, in particular a 5-level version (EQ-5D-5L), and a youth version (EQ-5D-Y) are covered. The history of the institutional and administrative framework within which the Group operated is also treated.

Handbook of Methods for Designing, Monitoring, and Analyzing Dose-Finding Trials gives a thorough presentation of state-of-the-art methods for early phase clinical trials. The methodology of clinical trials has advanced greatly over the last 20 years and, arguably, nowhere greater than that of early phase studies. The need to accelerate drug development in a rapidly evolving context of targeted therapies, immunotherapy, combination treatments and complex group structures has provided the stimulus to these advances. Typically, we deal with very small samples, sequential methods that need to be efficient, while, at the same time adhering to ethical principles due to the involvement of human subjects. Statistical inference is difficult since the standard techniques of maximum likelihood do not usually apply as a result of model misspecification and parameter estimates lying on the boundary of the parameter space. Bayesian methods play an important part in overcoming these difficulties, but nonetheless, require special consideration in this particular context. The purpose of this handbook is to provide an expanded summary of the field as it stands and also, through discussion, provide insights into the thinking of leaders in the field as to the potential developments of the years ahead. With this goal in mind we present: An introduction to the field for graduate students and novices A basis for more established researchers from which to build A collection of material for an advanced course in early phase clinical trials A comprehensive guide to available methodology for practicing statisticians on the design and analysis of dose-finding experiments An extensive guide for the multiple comparison and modeling (MCP-Mod) dose-finding approach, adaptive two-stage designs for dose finding, as well as dose-time-response models and multiple testing in the context of confirmatory dose-finding studies. John O'Quigley is a professor of mathematics and research director at the French National Institute for Health and Medical Research based at the Faculty of Mathematics, University Pierre and Marie Curie in Paris, France. He is author of Proportional Hazards Regression and has published extensively in the field of dose finding. Alexia Iasonos is an associate attending biostatistician at the Memorial Sloan Kettering Cancer Center in New York. She has over one hundred publications in the leading statistical and clinical journals on the methodology and design of early phase clinical trials. Dr. Iasonos has wide experience in the actual implementation of model based early phase trials and has given courses in scientific meetings internationally. Bjoern Bornkamp is a statistical methodologist at Novartis in Basel, Switzerland, researching and implementing dose-finding designs in Phase II clinical trials. He is one of the co-developers of the MCP-Mod methodology for dose finding and main author of the DoseFinding R package. He has published numerous papers on dose finding, nonlinear models and Bayesian statistics, and in 2013 won the Royal Statistical Society award for statistical excellence in the pharmaceutical industry.

The rapidly developing field of systems biology is influencing many aspects of biological research and is expected to transform biomedicine. Some emerging offshoots and specialized branches in systems biology are receiving particular attention and are becoming highly active areas of research. This collection of invited reviews describes some of the latest cutting-edge experimental and computational advances in these emerging sub-fields of systems biology. In particular, this collection focuses on the study of mammalian embryonic stem cells; new technologies involving mass-spectrometry proteomics; single cell measurements; methods for modeling complex stochastic systems; network-based classification algorithms; and the revolutionary emerging field of systems pharmacology.

Despite a half century of structural, biophysical and biochemical investigations of ribonucleic acids, they are still mysterious. RNAs stand at fertile crossroads of disciplines, integrating concepts from genomics, proteomics, dynamics as well as biochemistry and molecular biology. From 20 years it is clear, that genetic regulation of eukaryotic organisms has been misunderstood for the last years that the expression of genetic information is effected only by proteins. Basic understanding of nucleic acids has enhanced our foundation to probe novel biological functions. This is especially evident for RNA molecules whose functionality, maturation, and regulation require formation of correct secondary structure through encoded base-pairing interactions.

DNA methylation is a type of chemical modification of DNA that can be inherited without changing the DNA sequence. As such, it is part of the epigenetic code and is the most characterised epigenetic mechanism. DNA methylation involves the addition of a methyl group to DNA -- for example, to the number 5 carbon of the cytosine pyrimidine ring. DNA methylation is probably universal in eukaryotes. In humans, approximately 1% of DNA bases undergo DNA methylation. In adult somatic tissues, DNA methylation typically occurs in a CpG dinucleotide context; non-CpG methylation is prevalent in embryonic stem cells.In plants, cytosines are methylated both symmetrically (CpG or CpNpG) and asymmetrically (CpNpNp), where N can be any nucleotide. The methylation status of specific cytosines can be determined using methods based on bisulfite sequencing. This book presents leading-edge research advances in the field.

Cell-cell adhesion is fundamental for the development and homeostasis of animal tissues and organs. Adherens junctions (AJs) are the best understood cell-cell adhesion complexes. In this volume, internationally recognized experts review AJ biology over a wide range of organization; from atoms to molecules, to protein complexes, molecular networks, cells, tissues, and overall animal development. AJs have also been an integral part of animal evolution, and play central roles in cancer development, pathogen infection and other diseases. This book addresses major questions encompassing AJ biology. - How did AJs evolve? - How do cadherins and catenins interact to assemble AJs and mediate adhesion? - How do AJs interface with other cellular machinery to couple adhesion with the whole cell? - How do AJs affect cell behaviour and multicellular development? - How can abnormal AJ activity lead to disease? Valuable for both newcomers and experts in the field, this book offers a comprehensive resource for the research laboratory and a teaching tool for advanced undergraduate and graduate courses in cell and developmental biology.

Over the last decade the development of new molecular biology tools, advanced microscopy, live imaging and systems biology approaches have revolutionized our conception of how embryonic development proceeds. One fundamental aspect of development biology is the concept of morphogenesis: understanding how a group of multipotent cells organize and differentiate into a complex organ. In Kidney Development: Methods and Protocols, expert researchers in the field detail different approaches to tackle kidney development. These approaches include culture and live imaging aspects of kidney development, analyzing the 3-dimensional aspects of branching morphogenesis as well as nephrogenesis, manipulation of the gene/protein expression during kidney development as well as in the adult kidney, and how to assess kidney malformation and disease. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Kidney Development: Methods and Protocols seeks to aid scientists in the further study of the process of morphogenesis which is fundamental important not only for studying developmental biology but also for regenerative medicine.

Carl Edward Sagan's (1934-1996) one of the famous quotation was "Who are we? We find that we live on an insignificant planet of a humdrum star lost in a galaxy tucked away in some forgotten corner of a universe in which there are far more galaxies than people." From past to date, well-known molecules, enzymes, proteins, lipids and carbohydrates are studied in the pathogenesis of several diseases both as a diagnostic/prognostic biomarker and therapeutic agent. The underlying mechanism of unexplained diseases and failure of therapies are frequently studied with well-known biomarkers, but remain unclear in many cases. As Dr. Sagan said other keys are still waiting to be known in some forgotten corner of a body universe, we find strength to propose that one of them can be the growth factor with cytokine activity named "Midkine" This book summarizes the extensive up-to-date literature overeview with the lastest work of experts about midkine in a detailed format that conveys its role as both a pathologic factor and therapeutic agent.

Smoking is a greater cause of death and disability than any single disease, says the World Health Organisation. According to their figures, it is responsible for approximately five million deaths world-wide every year. Tobacco smoking is a known or probable cause of approximately 25 diseases including cancer, heart attacks and strokes. The WHO says that its impact on world health is still not fully assessed. This book offers leading edge research from around the globe with a focus on smoking cessation and the effects of passive smoking on health.

Develop the strong reasoning skills you'll need for competent and caring practice with An Introduction to Theory and Reasoning in Nursing. This proven book will help you understand theory, what it is, how it supports nurses and their practice and how you can use it to answer clinical questions and care for patients more effectively. -See theorists and their theories come to life with Theorist boxes that contain a brief synopsis of the theorist's life and a photo of the theorist (when available). -Access an alternative to nursing process care plans with a new research-validated reasoning model, the Clinical Reasoning Plan (CRP) that uses actual nursing case studies. -Increase your understanding of how theory and reasoning is used in clinical practice through Nursing Story boxes . -Clarify your understanding of individual support theories and nursing theories through Summaries that identify phenomenon, internal concepts or variables, propositions, external variables, and assumptions. -Increase your mastery of theory, research, and reasoning and their application to nursing practice through Chapter Overviews , Key Words in bold face type, Chapter Outlines. Chapter Introductions, Chapter Summaries, Learning Activities , and a comprehensive Glossary. -Go online to explore specific topics of interest through a wide range of up-to-date References . -Find the information you need fast with anytime, anywhere access to the fully searchable text online.

It is pointed out that a cancer stem cell is a type within a tumor that possesses the capacity of self-renewal and can give rise to the heterogeneous lineages of cancer cells, which comprise the tumor. It is emphasized that a unique feature of cancer stem cells is that, although conventional chemotherapy kills most cells in a tumor, cancer stem cells remain intact. Vast applications of the following specific stem cells in disease and tissue injury are discussed: embryonic stem cells, human mesenchymal stem cells, cancer stem cells, arterial stem cells, neural stem cells, cardiac stem cells, dental stem cells, limbal stem cells, and hematopoietic stem cells. Because human embryonic stem cells possess the potential to produce unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential in this volume. These cells are used in tissue engineering, regenerative medicine, pharmacological and toxicological studies, and fundamental studies of cell differentiation. It is pointed out that the formation of embryoid bodies, which are three-dimensional aggregates of embryonic cells, is the initial step in the differentiation of these cells. Therapeutic implications of signalling pathways in cancer stem cells are pointed out. Targeting self-renewal pathways in cancer stem cells are also included. Application of mesenchymal stem cells for treating ischemic brain injury is explained. Neural stem cells proliferation into the surrounding area of the traumatic brain injury is explained.

"

The advancements of medical technology, improvements in medical care, and increased patients' life span make pain research and related drug development high priorities for both the research community and pharmaceutical companies. Rapid development of basic science research tools, such as techniques of flurometric labeling, genomic and proteomic high throughput screening, and genetically modified animals, promotes the swift acceleration of pain research to a stage allowing integrated investigations of pain processing mechanisms at the single cell and/or molecule level, and in a spatially and temporally controlled manner. Using multidisciplinary approaches, we can dissect the complicity of the sensory circuits connecting peripheral stimulation to maladaptive changes in the sensory pathways as well as pain perceptions at the central nervous system. Pain Research: Methods and Protocols, Second Edition provides advanced techniques and animal models that are critical for integrated pain research. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Pain Research: Methods and Protocols, Second Edition serves as an ideal guide to novice pain researchers who may not have extensive experiences in the field, or to experienced pain researchers who would like to expand their research in new directions and/or to new mechanisms in different models.