The detrimental effects of incomplete data sets on the results of clinical trials are both well known and all too commonly recurrent. It is essential that the correct statistical methodology be applied in order to effectively analyse the results of trials affected by missing data.

Missing Data in Clinical Trials provides a comprehensive account of the problems arising when data from clinical and related studies are incomplete, and presents the reader with approaches to effectively address them. The text provides a critique of conventional and simple methods before moving on to discuss more advanced approaches. The authors focus on practical and modeling concepts, providing an extensive set of case studies to illustrate the problems described.

Provides a practical guide to the analysis of clinical trials and related studies with missing data. Examines the problems caused by missing data, enabling a complete understanding of how to overcome them. Presents conventional, simple methods to tackle these problems, before addressing more advanced approaches, including sensitivity analysis, and the MAR missingness mechanism. Illustrated throughout with real-life case studies and worked examples from clinical trials. Details the use and implementation of the necessary statistical software, primarily SAS.

Missing Data in Clinical Trials has been developed through a series of courses and lectures. Its practical approach will appeal to applied statisticians and biomedical researchers, in particular those in the biopharmaceutical industry, medical and public health organisations. Graduate students of biostatistics will also find much of benefit.

Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics

The inflammasome is a protein complex composed of an intracellular sensor-typically a Nod-like receptor (NLR), the precursor procaspase-1, and the adaptor ASC. Inflammasome activation leads to the maturation of caspase-1 and the processing of its substrates, IL-1 and IL-18. The inflammasome has been implicated numerous diseases, and blockade of inflammasome-derived IL-1 has beneficial effects on several of these diseases. Different books have been edited about the biology of inflammasomes and about methods to study, however, the implication of this complex in the different diseases and pathological conditions show the need of a book about the clinical implications and therapeutic options. This project will show the context where inflammasomes are being studied and the molecular implications in the medical and clinical contexts. Other important topic of the inflammasomes will be the development of pharmacological inhibitors in order to improve new clinical applications. In this sense, we can find new drugs with inhibitory effects or old drugs with an inhibitory potential effect. There is a need for re-establishing the real benefits of the inflammasome inhibitions in pathological situations and the management of the differents diseases where inflammasomes are implicated.

Adequate health and health care is no longer possible without proper data supervision from modern machine learning methodologies like cluster models, neural networks, and other data mining methodologies. The current book is the first publication of a complete overview of machine learning methodologies for the medical and health sector, and it was written as a training companion, and as a must-read, not only for physicians and students, but also for any one involved in the process and progress of health and health care. In this second edition the authors have removed the textual errors from the first edition. Also, the improved tables from the first edition, have been replaced with the original tables from the software programs as applied. This is, because, unlike the former, the latter were without error, and readers were better familiar with them. The main purpose of the first edition was, to provide stepwise analyses of the novel methods from data examples, but background information and clinical relevance information may have been somewhat lacking. Therefore, each chapter now contains a section entitled "Background Information". Machine learning may be more informative, and may provide better sensitivity of testing than traditional analytic methods may do. In the second edition a place has been given for the use of machine learning not only to the analysis of observational clinical data, but also to that of controlled clinical trials. Unlike the first edition, the second edition has drawings in full color providing a helpful extra dimension to the data analysis. Several machine learning methodologies not yet covered in the first edition, but increasingly important today, have been included in this updated edition, for example, negative binomial and Poisson regressions, sparse canonical analysis, Firth's bias adjusted logistic analysis, omics research, eigenvalues and eigenvectors.

This monograph focuses on modern femtosecond laser microscopes for two photon imaging and nanoprocessing, on laser tweezers for cell micromanipulation as well as on fluorescence lifetime imaging (FLIM) in Life Sciences. The book starts with an introduction by Dr. Wolfgang Kaiser, pioneer of nonlinear optics and ends with the chapter on clinical multiphoton tomography, the novel high resolution imaging technique. It includes a foreword by the nonlinear microscopy expert Dr. Colin Sheppard. Contents Part I: Basics Brief history of fluorescence lifetime imaging The long journey to the laser and its use for nonlinear optics Advanced TCSPC-FLIM techniques Ultrafast lasers in biophotonics Part II: Modern nonlinear microscopy of live cells STED microscopy: exploring fluorescence lifetime gradients for super-resolution at reduced illumination intensities Principles and applications of temporal-focusing wide-field two-photon microscopy FLIM-FRET microscopy TCSPC FLIM and PLIM for metabolic imaging and oxygen sensing Laser tweezers are sources of two-photon effects Metabolic shifts in cell proliferation and differentiation Femtosecond laser nanoprocessing Cryomultiphoton imaging Part III: Nonlinear tissue imaging Multiphoton Tomography (MPT) Clinical multimodal CARS imaging In vivo multiphoton microscopy of human skin Two-photon microscopy and fluorescence lifetime imaging of the cornea Multiscale correlative imaging of the brain Revealing interaction of dyes and nanomaterials by multiphoton imaging Multiphoton FLIM in cosmetic clinical research Multiphoton microscopy and fluorescence lifetime imaging for resection guidance in malignant glioma surgery Non-invasive single-photon and multi-photon imaging of stem cells and cancer cells in mouse models Bedside assessment of multiphoton tomography

Signal Processing for Neuroscientists, Second Edition provides an introduction to signal processing and modeling for those with a modest understanding of algebra, trigonometry and calculus. With a robust modeling component, this book describes modeling from the fundamental level of differential equations all the way up to practical applications in neuronal modeling. It features nine new chapters and an exercise section developed by the author. Since the modeling of systems and signal analysis are closely related, integrated presentation of these topics using identical or similar mathematics presents a didactic advantage and a significant resource for neuroscientists with quantitative interest. Although each of the topics introduced could fill several volumes, this book provides a fundamental and uncluttered background for the non-specialist scientist or engineer to not only get applications started, but also evaluate more advanced literature on signal processing and modeling.

This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.

The Epigenetics of Autoimmunity covers a topic directly related to translational epigenetics. Via epigenetic mechanisms, a number of internal and external environmental risk factors, including smoking, nutrition, viral infection and the exposure to chemicals, could exert their influence on the pathogenesis of autoimmune diseases. Such factors could impact the epigenetic mechanisms, which, in turn, build relationship with the regulation of gene expression, and eventually triggering immunologic events that result in instability of immune system. Since epigenetic aberrations are known to play a key role in a long list of human diseases, the translational significance of autoimmunity epigenetics is very high. To bridge the gap between environmental and genetic factors, over the past few years, great progress has been made in identifying detailed epigenetic mechanisms for autoimmune diseases. Furthermore, with rapid advances in technological development, high-throughput screening approaches and other novel technologies support the systematic investigations and facilitate the epigenetic identification. This book covers autoimmunity epigenetics from a disease-oriented perspective and several chapters are presented that provide advances in wide-spread disorders or diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1DM), systemic sclerosis (SSc), primary Sjoegren's syndrome (pSS) and autoimmune thyroid diseases (AITDs). These emerging epigenetic studies provide new insights into autoimmune diseases, raising great expectations among researchers and clinicians. This seminal book on this topic comprehensively covers the most recent advances in this exciting and rapidly developing new science. They might reveal not only new clinical biomarkers for diagnosis and disease progression, but also novel targets for potential epigenetic therapeutic treatment.

Molecular-Genetic and Statistical Techniques for Behavioral and Neural Research presents the most exciting molecular and recombinant DNA techniques used in the analysis of brain function and behavior, a critical piece of the puzzle for clinicians, scientists, course instructors and advanced undergraduate and graduate students. Chapters examine neuroinformatics, genetic and neurobehavioral databases and data mining, also providing an analysis of natural genetic variation and principles and applications of forward (mutagenesis) and reverse genetics (gene targeting). In addition, the book discusses gene expression and its role in brain function and behavior, along with ethical issues in the use of animals in genetics testing. Written and edited by leading international experts, this book provides a clear presentation of the frontiers of basic research as well as translationally relevant techniques that are used by neurobehavioral geneticists.

This volume presents the latest developments and techniques used to study the physiopathology, diagnosis, and treatment of pre-eclampsia. Written for clinicians, obstetricians, basic scientists, researchers, and students the chapters in this book provide methods to study placental function using in vitro and ex vivo model systems, comprehensive genetic analysis of pre-eclampsia, identifying critical angiogenic factors associated with the development of pre-eclampsia, and controlled experiments that investigate potential therapies. 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, tips on troubleshooting and avoiding known pitfalls, as well as a description of the limitations and advantages of the described techniques. Cutting-edge and comprehensive, Pre-Eclampsia: Methods and Protocols is a valuable resource for anyone interested in learning more about the critical role of the placenta in the maternal-fetal relationship.

The second of two companion books which address the biology and clinical aspects of prostate cancer. This volume, Prostate Cancer: Molecular & Diagnostic Imaging and Treatment Stategies, discusses both classic and the most recent imaging approaches for detection, early diagnosis and treatment of prostate cancer. The companion title, Cell & Molecular Biology of Prostate Cancer, covers classic and modern cell and molecular biology as well as genetics, epigenetics, mitochondrial dysfunctions and apoptosis, cancer stem cells, angiogenesis, progression to metastasis, and treatment strategies including clinical trials related to prostate cancer. Taken together, these volumes form one comprehensive and invaluable contribution to the literature.

Learn not only how to recognize high-quality research, but how to improve your own research and apply it to patient care. Plus, find out how to start a journal club, write quality case reports and how to most effectively present your research to others. This book is ideal guide for students at both graduate and undergraduate levels who might be having difficulty with research concepts as well as for practiced clinicians interested in a fresh approach to clinical research. * A jargon-free guide to understanding and conducting research * Uses metaphors, visual images, and examples to simplify complex research concepts * Includes easy-to-do computer exercises to help you understand statistical concepts

This book, written by members of the European network PROTEOSTASIS, provides an up-to-date review of the research regarding protein homeostasis in health and disease. With new discoveries contributing to the increasing complexity of this topic, the book offers a detailed overview of the pathways regulating protein homeostasis, including autophagy and the ubiquitin protein family. Following a basic introduction, it explains how defects in protein homeostasis contribute to numerous pathologies, including cancer, neurodegeneration, inflammation and a number of rare diseases. In addition, it discusses, the role of protein homeostasis in cellular development and physiology. Highlighting the latest research in the field of protein homeostasis and its implications for various clinically relevant diseases, the book appeals to researchers and clinicians, while also offering a reference guide for scholars who are new to the field.

The book contains the refereed contributions from the 45th Annual Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) 2017. This volume covers cross-disciplinary work on a broad range of topics related to the dynamics of oxygen transport: microcirculation and vascular medicine; O2 deficiency and its impact on molecular processes in cells and tissues; cellular metabolism and mitochondrial function; multimodal functional imaging; mathematical modeling; the clinical relevance of oxygen supply as well as therapeutic interventions (e.g. in oncology or critical care medicine). The annual meetings of ISOTT bring together scientists from diverse fields (medicine, physiology, mathematics, biology, chemistry, physics, engineering, etc.) in a unique international forum. The book includes sections on brain oxygenation and function, NIRS oxygenation measurements, tumor oxygenation, cell metabolism, tissue oxygenation and treatment, methodical aspects of O2 measurements and physicochemical aspects of oxygen diffusion. Chapters 3, 24, 49 and 51 of this book are open access under a CC BY 4.0 license.

Progress in Drug Research is a prestigious book series which provides extensive expert-written reviews on a wide spectrum of highly topical areas in current pharmaceutical and pharmacological research. Founded in 1959 by its current editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

Mitochondrial diseases comprise a clinically and genetically heterogeneous group of rare disorders that may affect virtually any system of the body at any age. Due to their complexity, understanding and diagnosing these diseases requires a multidisciplinary approach. This book provides an update on the major features of human mitochondrial diseases: genetic bases, pathophysiology, diagnosis, and treatment, and of the new technologies involved in the diagnosis and on the characterization of patients. The 11 chapters examine the unique complex interactions between the mitochondrial and the nuclear genomes involved in the biogenesis and the regulation of the mitochondrial respiratory chain, and their relevance to human disease. We discuss the traditional biochemical and genetic approaches, as well as the new omic technologies, and the cellular and animal models used in mitochondrial research. The last chapter is dedicated to the current treatment options. Authors are worldwide experts in these fields and integrate expertise in both basic science and clinical research. This book is particularly important for both scientists and clinicians interested in the diagnosis and treatment of these diseases.

Cancer genetics is a quickly growing field within oncology. The ability to identify individuals at high risk for cancer improves the chance of early prevention and detection of cancer. The results of genetic testing affect quality of life, employment, and ability to be insured. This volume provides an overview of cancer genetics, inherited cancer susceptibility, and available services and testing, including both the risks and benefits of testing. Some of the topics covered include: genetics of breast and ovarian cancer; testing minors for inherited cancer risk; chemoprevention of heritable cancer risk; genetics of colorectal cancer; insurance issues in genetic testing for cancer; ethical and legal issues in genetic testing for cancer susceptibility; testing for breast cancer risk in the Ashkenazim; estimating individualized risk of breast cancer; genetic counselling for the individual with inherited cancer susceptibility; and components of a genetic cancer risk clinic.

This book highlights the latest research presented at the International Conference on Translational Medicine and Imaging (ICTMI) 2017. This event brought together the world's leading scientists, engineers and clinicians from a wide range of disciplines in the field of medical imaging. Bioimaging has continued to evolve across a wide spectrum of applications from diagnostics and personalized therapy to the mechanistic understanding of biological processes, and as a result there is ever-increasing demand for more robust methods and their integration with clinical and molecular data. This book presents a number of these methods.

Cancer metabolomics is a rapidly evolving field that aims for a comprehensive dissection of the metabolic phenotypes and functional network of metabolites in human cancers. State of the art metabolomics tools have been developed and applied to studying cancer metabolism and developing metabolic targets for improved diagnosis, prognosis and therapeutic treatment of human cancers. Chapters are written by subject experts in the field of cancer metabolomics with cross-disciplinary contributions. Coverage includes advanced metabolomics technologies and methodologies, including chemical isotope labelling liquid chromatography - mass spectrometry, capillary ion chromatography - mass spectrometry, 2-D gas chromatography - mass spectrometry, capillary electrophoresis - mass spectrometry, nuclear magnetic resonance spectroscopy, shotgun lipidomics, tracer-based metabolomics, microbial metabolomics, mass spectrometry imaging for single cell metabolomics and functional metabolomics. In addition, the book highlights new discoveries in cancer metabolism such as hypoxia inducible factor pathway, isocitrate dehydrogenase 1 mutation and oncometabolites. Finally, contributors focus on the translational applications of metabolomics in human cancers such as glioma, head and neck cancer, and gastric cancer. This new volume will be a unique reference source for cancer researchers and promote applications of metabolomics in understanding cancer metabolism.

The world is faced with an epidemic of metabolic diseases such as obesity and type 2 diabetes. This is due to changes in dietary habits and the decrease in physical activity. Exercise is usually part of the prescription, the first line of defense, to prevent or treat metabolic disorders. However, we are still learning how and why exercise provides metabolic benefits in human health. This open access volume focuses on the cellular and molecular pathways that link exercise, muscle biology, hormones and metabolism. This will include novel "myokines" that might act as new therapeutic agents in the future.

This book offers a summary and discussion of the advances of inflammation and infection in various cancers. The authors cover the classically known virus infections in cancer, novel roles of other pathogens (e.g. bacteria and fungi), as well as biomarkers for diagnosis and therapy. Further, the chapters highlight the progress of immune therapy, stem cells and the role of the microbiome in the pathophysiology of cancers. Readers will gain insights into complex microbial communities, that inhabit most external human surfaces and play a key role in health and disease. Perturbations of host-microbe interactions often lead to altered host responses that can promote cancer development. Thus, this book highlights emerging roles of the microbiome in pathogenesis of cancers and outcome of therapy. The focus is on mechanistic concepts that underlie the complex relationships between host and microbes. Approaches that can inhibit infection, suppress chronic inflammation and reverse the dysbiosis are discussed, as a means for restoring the balance between host and microbes. This comprehensive work will be beneficial to researchers and students interested in infectious diseases, microbiome, and cancer as well as clinicians and general physiologists.

In this book, renowned scientists describe the role of steroid chirality and modification of lipid membrane physical properties in the modulation of G protein-coupled receptors and ion channels. The application of commonly-used technical approaches such as mass spectrometry and nucleic magnetic resonance transfer spectroscopy for studies on cholesterol distribution and alteration of lipid bilayer characteristics is also discussed. This book offers comprehensive insights into the current understanding of cholesterol-driven modulation of protein function via mechanisms that extend beyond lipid-protein direct interactions. In the first part, the chapters introduce the reader to the use of the chemical derivatives of cholesterol as a valuable laboratory tool in the studies of cholesterol-driven modulation of protein function. In the second part, examples of cholesterol-induced changes in membrane physical characteristics are presented and discussed in light of their multifaceted contribution to the effect of cholesterol on protein function. The book will be of interest to undergraduate and graduate students as well as basic science and medical researchers with a keen interest in the biophysical properties of cholesterol and physiological consequences of cholesterol presence in biological systems.

This book collects and reviews, for the first time, a wide range of advances in the area of human aging biomarkers. This accumulated data allows researchers to assess the rate of aging processes in various organs and systems, and to individually monitor the effectiveness of therapies intended to slow aging. In an introductory chapter, the editor defines biomarkers of aging as molecular, cellular and physiological parameters that demonstrate reproducible changes - quantitative or qualitative - with age. The introduction recounts a study which aimed to create a universal model of biological age, whose most predictive parameters were albumin and alkaline phosphatase (indication liver function), glucose (metabolic syndrome), erythrocytes (respiratory function) and urea (renal function). The book goes on to describe DNA methylation, known as the "epigenetic clock," as currently the most comprehensive predictor of total mortality. It is also useful for predicting mortality from cancer and cardiovascular diseases, and for analyzing the effects of lifestyle factors including diet, exercise, and education. Individual contributions draw additional insight from research on genetics and epigenetic aging markers, and immunosenescence and inflammaging markers. A concluding chapter outlines the challenge of integrating of biological and clinical markers of aging. Biomarkers of Human Aging is written for professionals and practitioners engaged in the study of aging, and will be useful to both advanced students and researchers.

This collection thoroughly explores the dynamic and ever-developing field of hemostasis and thrombosis diagnostics and research. After an introductory section covering the basics and preanalytical issues, the book continues with in-depth sections that explore how to get the best outcomes from routine coagulation and specialized hemostasis assays, thrombophilia-related techniques, investigations into bleeding disorders, as well as performance of global assays of hemostasis, and finally post-analytical issues in hemostasis and thrombosis testing. 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. Comprehensive and practical, Hemostasis and Thrombosis: Methods and Protocols serves as an ideal resource for researchers and diagnostic laboratories seeking expert guidance and working to identify the best methodologies to pursue hemostasis and thrombosis testing.