Group sequential methods answer the needs of clinical trial monitoring committees who must assess the data available at an interim analysis. These interim results may provide grounds for terminating the study-effectively reducing costs-or may benefit the general patient population by allowing early dissemination of its findings. Group sequential methods provide a means to balance the ethical and financial advantages of stopping a study early against the risk of an incorrect conclusion.
Group Sequential Methods with Applications to Clinical Trials describes group sequential stopping rules designed to reduce average study length and control Type I and II error probabilities. The authors present one-sided and two-sided tests, introduce several families of group sequential tests, and explain how to choose the most appropriate test and interim analysis schedule. Their topics include placebo-controlled randomized trials, bio-equivalence testing, crossover and longitudinal studies, and linear and generalized linear models.
Research in group sequential analysis has progressed rapidly over the past 20 years. Group Sequential Methods with Applications to Clinical Trials surveys and extends current methods for planning and conducting interim analyses. It provides straightforward descriptions of group sequential hypothesis tests in a form suited for direct application to a wide variety of clinical trials. Medical statisticians engaged in any investigations planned with interim analyses will find this book a useful and important tool.

Handbook of Animal Models of Infection is a complete revision of a three-volume text that was published in 1986. It incorporates the major advances in the field during the past decade, in particular those concerning molecular biological procedures and new models that have been developed. It focuses on both methods and techniques, which makes it an essential and comprehensive reference as well as a benchtop manual. The Handbook will help investigators save time and effort in formulating an approach to test a new potential therapeutic agent or combination of agents for "in vivo" efficacy and to position the therapy for specific infections where it may have therapeutic promise. The book is divided into five sections; the first covering the general methodologies, followed by sections describing experimental bacterial, mycotic, parasitic, and viral infections.
Key Features
* Discusses ethical and safety aspects in an introductory background section
* Covers principles of animal care and current techniques appropriate for the use of animal models of infection
* Details a wide range of animals including rodents, rabbits, cats, and primates
* Provides hands-on descriptions of how to set up the model
* Discusses the major advantages and limitations of each model
* Ensures full coverage of bacterial, fungal, viral, and parasitic infections

"In Vitro" Methods in Pharmaceutical Research provides a comprehensive guide to laboratory techniques for evaluating "in vitro" organ toxicity using cellular models. Step-by-step practical tips on how to perform and interpret assays for drug metabolism and toxicity assessment are provided, along with a comparison of different techniques available. It is a welcome addition to the literature at a time when interest is growing in cellular "in vitro" models for toxicology and pharmacology studies.
Key Features
* Meets the continuing demand for information in this field
* Compares "In Vitro" techniques with other methods
* Describes cell-culture methods used to investigate toxicity in cells derived from different organs
* Includes contributions by leading experts in the field

Preface by T. Morrison, Director-General of the European Diagnostic Manufacturers Association. Contributors: W. Kewenig; G. Forlani, J. Marriage, G. Ulloa This book is based upon a report prepared at the request of the European Commission. Its purpose is to set out the existing laws regulating the development, production, distribution and use of in vitro diagnostic medical devices (IVDMD) in the U.K., Germany, France, Italy and Spain. Each national section has the same structure and covers the same ground in order to enable comparisons. IVDM Devices includes not only reagents, but also technical instruments, or combination of both, for human use. The book is directed towards industry and the regulation is covered with a high degree of specificity. This reference book, completely written in English, is the only comprehensive exposition of the laws of the five countries regarding IVDM Devices available. It is also the most convenient means of comparing those laws. As such, it will be a useful guide to all IVDM Devices manufacturers interested in the European market.

As the drug discovery process shifts more and more toward specifically targeting pathways and molecules, model systems continue to increase in importance, and the mouse, with its versatility, ease of use, and remarkable similarity to the human genome, has clearly risen to the forefront of animal model studies. In Mouse Models for Drug Discovery: Methods and Protocols, experts in the field present some background for those less familiar with mice as experimental model platforms as well as a collection of techniques involving general methods as well as specific disease topics such as type 1 and 2 diabetes, cardiovascular disease, arthritis, skin disorders, cancer, the use of behavioral models for depression and anxiety, neurodegenerative diseases, neuromuscular diseases, and infectious diseases. 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 notes on troubleshooting and avoiding known pitfalls.

Authoritative and easy-to-use, Mouse Models for Drug Discovery: Methods and Protocols will stimulate those not familiar with the power of the mouse and its potential for the drug discovery process, and it will encourage the development of new models and new ways to utilize existing models in order to further the use of this dynamic animal in this vital field."

Molecular diagnostic procedures have been described in a number of recent books and articles. However, these publications have not focused on virus detection, nor have they provided practical protocols for the newer molecular methods.
Written by the inventors or principal developers of these technologies, Molecular Methods for Virus Detection provides both reviews of individual methods and instructions for detecting virus nucleic acid sequences in clinical specimens. Each procedure includes quality assurance protocols that are often ignored by other methodology books. Molecular Methods for Virus Detection provides clinically relevant procedures for many of the newer diagnostic methodologies.
Key Features
* Provides state-of-the-art PCR methods for amplification, quantitation, " in situ" hybridization, and multiplex reactions
* Goes beyond PCR with protocols for 3SR, NASBA, LCR, SDA, and LAT
* Covers important virus detection methods such as "in situ" hybridization; Southern, dot, and slot blots; branched chain signal amplification; and chemiluminescence
* Includes quality control information crucial in research and clinical laboratories
* Most chapters are written by the inventors and principal developers of the methodologies
* Includes color plates, 77 figures, and 18 tables

This book is intended as a practical primer on the Pap test. Using bold text, tables, and highlighted areas, this book offers a user-friendly text on Pap test fundamentals so readers may find specific information effortlessly. The book is a useful tool for cytotechnologists and cytopathologists, as well as those in training. Readers preparing for various proficiency and licensing examinations will also find helpful information throughout.

This book summarizes the contributions at an April 2016 conference held at Albany Medical College, Reproductive Ethics: New Challenges and Conversations. Reproductive ethics does not suffer from a lack of challenging issues, yet a few "hot button" issues such as abortion and surrogacy seem to attract most of the attention, while other issues and dilemmas remain relatively underdeveloped in bioethics literature. The goal of this book is to explore and expand the range of topics addressed in reproductive ethics. This is a multi-disciplinary book bringing together philosophers, clinicians, sociologists, anthropologists, and other scholars whose research or clinical interests touch reproductive issues. The results of this compilation are a comprehensive and unique discussion of the evolving issues in the rapidly changing field. The majority of the popular reproductive ethics anthologies were published at least 10 years ago. The field of reproductive ethics would benefit from a new anthology that addresses some of the perennial dilemmas in reproductive ethics (e.g. abortion, sex selection) from updated perspectives and that also covers new technologies that have emerged only in the last few years, such as social egg freezing.

Since the publication of the popular first edition, the explosion of DNA sequence information, the access to bioinformatics and mutation databases coupled with the ability to readily detect and confirm mutations has cemented the role of molecular diagnostics in medicine and, in particular, mutation detection by the polymerase chain reaction (PCR). In PCR Mutation Detection Protocols, Second Edition, expert researchers bring the subject up-to-date with key protocols involving the PCR and its many various incarnations such as SSCP, CSGE, and dHPLC. The volume also addresses key areas such as Southern blotting, accurate diagnostics with high throughput, as well as microarray systems. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief introductions their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes which provide the often hard to find information that may mean the difference between the success and failure of the method. Authoritative and cutting-edge, PCR Mutation Detection Protocols, Second Edition aims to stimulate postgraduate scientists, researchers, and clinicians already engaged in the area and to provide an important first step for those new to this practice wanting to adopt the powerful and essential technique in their own laboratories.

This volume provides a transdisciplinary and translational review of many of the leading murine models used to study the mechanisms, mediators and biomarkers linking energy balance to cancer. It provides a review of murine models that should be of interest to basic, clinical and applied research investigators as well as nutrition scientists and students that work in cancer prevention, cancer control and treatment. The worldwide obesity pandemic has been extensively studied by epidemiologic and observational studies and even, in some cases, by randomized controlled trials. However, the development and control of obesity, its comorbidities and its impact on cancer usually occurs over such long periods that it is difficult, if not impossible to conduct randomized controlled trials in humans to investigate environmental contributions to obesity, energy balance and their impact on cancer. In contrast, model organisms, especially mice and rats, provide valuable assets for performing these studies under rigorously controlled conditions and in sufficient numbers to provide statistically significant results. In this volume, many of the leading and new murine models used to study the mechanisms and mediators linking cancer with obesity, sleep, exercise, their modification by environment and how they may continue to be used to further elucidate these relations as well as to explore preclinical aspects of prevention and/or therapeutic intervention are considered. This volume provides an important compilation and analysis of major experimental systems and principles for further preclinical research with translational impact on energy balance and cancer.

Known for flexibility and robustness, PCR techniques continue to improve through numerous developments, including the identification of thermostable DNA polymerases which exhibit a range of properties to suit given applications. PCR Protocols, Third Edition selects recently developed tools and tricks, contributed by field-leading authors, for the significant value that they add to more generally established methods. Along with the cutting-edge methodologies, this volume describes many core applications, such as PCR cloning and sequencing, expression, copy number or methylation profile analysis, 'DNA fingerprinting', diagnostics, protein engineering, interaction screening as well as a chapter highlighting workflow considerations and contamination control, crucial for all PCR methods. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary reagents and materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, PCR Protocols, Third Edition seeks to further elucidate this essential technique while also providing core principles with broad applications for scientists of all backgrounds.

Somuchofwhatweknowaboutthepathogenesisofhumandiseasehascomefromthe systematic and careful study of histological material. Indeed, every internal medicine discipline has its landmark papers describing the clinico-pathological correlations. However, increasingly, it is molecular and cellular biology that provides the necessary mechanistic insights. For many years, it was thought that the two skill sets were mutually exclusive, but we hope that this book shows that this is not necessarily so. Implicitinthescienceofhistologyisthepreservationandarchivingoftissue.PartIof the book concentrates on the preparation of tissue, providing an overview of fixation, embedding, and processing (Chapter 1), and in Chapters 2 and 3, the required techniques for the retrieval of RNA from histological sections. Both routine and specialist histological staining techniques are provided in Part II. These include pro- cols for immuno (Chapters 4-7), lectin (Chapter 8), and hybridization (Chapter 9) histochemistry, histologicalstaining (Chapters10and11), aswellasspecificmethods for the in situ identification of hypoxia (Chapter 12) and apoptosis (Chapter 13). Finally, Part III details advances in imaging (Chapters 14-16) and image analysis (Chapter 17). It is hoped that this volume will provide molecular biologists with the basic his- chemical techniques and histologists with the molecular techniques to realise the potential of their resource. We are indebted to the authors for their generosity in sharing these protocol

The term humanized mouse in this text refers to a mouse in which human tissues and cells have been transplanted and show the same biological function as they do in the human body. That is, the physiological properties and functions of tra- planted human tissues and cells can be analyzed in the mouse instead of using a living human body. It should therefore be possible to study the pathophysiology and treatment of human diseases in mice with good reproducibility. Thus, the hum- ized mouse can be used as a potent tool in both basic and clinical research in the future. The development of appropriate immunodeficient mice has been indispensable in the creation of the humanized mouse, which has been achieved through many years of efforts by several laboratories. The first stage on the road to the humanized mouse was the report on nude mice by Isaacson and Cattanach in 1962. Thereafter, nude mice were studied in detail by Falanagan and, in 1968, Pantelouris found that these mice have no thymus gland, which suggested that the mice lack transplan- tion immunity against xenografts such as human hematopoietic stem cells. At the Nude Mouse Workshops (organized by Regard, Povlsen, Nomura and colleagues) that were held nine times between 1972 and 1997, the possibility of creating a humanized mouse using nude mice was extensively examined. The results, however, showed that certain human cancers can be engrafted in nude mice, but unfortunately engraftment of normal human tissue was almost impossible.

Metastatic dissemination of cancer is a main cause of cancer related deaths, therefore biological mechanisms implicated in metastatic process presents an essential object of cancer research. This research requires creation and utilization of adequate laboratory models. The book describes main approaches to model processes of metastatic cancer dissemination and metastases development. The book is structured in according with various metastatic pathways reflecting molecular specificity of metastatic process as well as anatomical specificity of aria of dissemination. Each chapter is introduced by short discussion of clinical aspects of certain metastatic pathway. Especial attention is paid for methods of visualization, quantification and analysis of the modeled metastases. Additional chapter is devoted to methods of mathematic modeling of tumor spread. The data presented in the book may be helpful for cancer researchers and oncologists.

Scientists challenging dominant paradigms are either ignored or attacked by the scientific mainstream. This book, however, contains a selection of scientific papers presented at the two last GIRI meetings (International Research Group on Very Low Dose and High Dilution Effects). The majority of these papers present results performed with succussed high dilutions (homeopathic dilutions), even beyond the Avogrado number. All presented models are classified, and their interpretation is possible either in the mechanistic paradigm or in an information paradigm. This new field of research introduces new scientific concepts which are supported by experimental results. Furthermore, this nascent science is totally concerned with living organisms and, as such, it becomes necessary to define information' brought by non-molecular high dilutions. This book presents brain-storming work of this research group and is one of the starting points of a scientific evolution.

During the past two decades, many books, governmental reports and regu lations on safety measures against chemieals, fire, microbiological and radioactive hazards in laboratories have been published from various coun tries. These topics have also been briefly discussed in books on laboratory planning and management. The application ofvarious scientific instruments based on different ionizing and non-ionizing radiations have brought new safety problems to the laboratory workers of today, irrespective of their scientific disciplines, be they medicine, natural or life sciences. However, no comprehensive laboratory handbook dealing with aIl these hazards, some of which are recently introduced, had so far been available in a single volume. Therefore, it was thought worthwhile to publish this Handbook on safety and health measures for laboratories, with contributions from several experts on these subjects. As this second edition of the Handbook, like the first edition, is a multiauthor volume, some duplication in conte nt among chapters is unavoidable in order to maintain the context of a chapter as weIl as make each chapter complete. An attempt has also been made to maintain the central theme, which is how to work in a laboratory with maximum possible environmental safety."

Technological advances have revolutionized the way we manage information in our daily workflow. The medical field has especially benefitted from these advancements, improving patient treatment, health data storage, and the management of laboratory samples and results.Laboratory Management Information Systems: Current Requirements and Future Perspectives responds to the issue of administering appropriate regulations in a medical laboratory environment in the era of telemedicine, electronic health records, and other e-health services. Exploring concepts such as the implementation of ISO 15189:2012 policies and the effects of e-health application, this book is an integral reference source for researchers, academicians, students of health care programmes, health professionals, and laboratory personnel.

A comprehensive description of macroscopic, microscopic, and radiological methods for the diagnosis of bone diseases. The book presents all the procedures involved in diagnosis, using not only radiological and histological techniques, but also modern immunohistochemical and scintigraphic methods. Succinct and well-structured therapeutic recommendations are provided for an array of bone diseases, making this a practice-oriented reference work for pathologists, radiologists, rheumatologists, and orthopedists.

Recently, important new findings in the polyamine field and a variety of new experimental systems have revolutionized the study of these ubiquitous cellular components, essential for normal growth and development. In "Polyamines: Methods and Protocols," leading researchers contribute an extensive collection of up-to-date laboratory techniques for the further pursuit of polyamine study. The volume delves into vital subjects such as neoplasia studies with animal models and human patients, therapeutic roles for polyamine inhibitors and analogs, polyamine metabolism and oxidative damage, polyamines as regulators of critical ion channels, as well as polyamine transport systems and polyamine-responsive genes. 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 expert notes on troubleshooting and avoiding known pitfalls.

Comprehensive and cutting-edge, "Polyamines: Methods and Protocols" provides a key resource for all scientists pursuing the study of this dynamic and significant aspect of cellular biology."

Jurgen Schulte and Christian Endler met in 1990 at an international conference on the Structure of Water held in the Lecture Halls of the University of Graz (Austria). Disappointed by the lack of a systematic strategy of research into the physics of homoeopathy Jurgen Schulte started to work on the establishment of scientifically acceptable research standards in physics of homoeopathy and encouraged academic researchers to establish a coordinated and focused research strategy. In 1994, with the help of major representatives of the international research community, they edited one of the fIrst academic interdisciplinary books on Ultra High Dilution and homoeopathy that underwent a rigorous scientific international referee process before publishing. Due to the dedicated help of the prominent referees (BD Josephson, Nobel Laureate, Cavendish Lab. , Cambridge; M Bastide, Fac de Pharmacy, University Montpellier; RG Jahn, Aerospace Science, Princeton University), the book 1994 was quickly considered a mile stone and turning point for the scientific approach of research into Ultra High Dilution and homoeopathy. Since then the academic research community has grown considerably and many international conferences have been held. Today, research into homoeopathy is to be accepted by the European Union as part of the academic sciences, worthy to be funded at European Union level; an effort that took many years of research coordination and research strategy development. Excerpts of the Research Strategy of the European Committee for Homoeopathy (ECH) have been included in this book.

John R. Petersen and Amin A. Mohammad, along with a panel of leading basic and clinical investigators, review those CE methods that are now replacing many routine serum and blood tests in clinical and forensic laboratories. Major areas reviewed include the coating of columns; the analysis of serum, urine, and CSF proteins and paraproteins; abnormal hemoglobins and hemoglobin Alc; peptides, amino and organic acids; therapeutic drugs; drugs of abuse; viral load; and short tandem repeats (STR). The methods discussed include capillary zone, micellar, electrokinetic, capillary gel, and non-aqueous electrophoresis. Innovative and highly practical, Clinical and Forensic Applications of Capillary Electrophoresis demonstrates the power and versatility of CE-not only to develop new assays, but also to markedly simplify today's clinical and forensic laboratory methodology.

This book covers new techniques in protein NMR, from basic principles to state-of-the-art research. It covers a spectrum of topics ranging from a "toolbox" for how sequence-specific resonance assignments can be obtained using a suite of 2D and 3D NMR experiments and tips on how overlap problems can be overcome. Further topics include the novel applications of Overhauser dynamic nuclear polarization methods (DNP), assessing protein structure, and aspects of solid-state NMR of macroscopically aligned membrane proteins. This book is an ideal resource for students and researchers in the fields of biochemistry, chemistry, and pharmacology and NMR physics. Comprehensive and intuitively structured, this book examines protein NMR and new novel applications that include the latest technological advances. This book also has the features of: * A selection of various applications and cutting-edge advances, such as novel applications of Overhauser dynamic nuclear polarization methods (DNP) and a suite of 2D and 3D NMR experiments and tips on how overlap problems can be overcome * A pedagogical approach to the methodology * Engaging the reader and student with a clear, yet critical presentation of the applications

Reviewing the topic from antiquity to the present day, this book examines the debate over the use of animals in research in a fair and balanced way. The debate over the use of nonhuman animals in experimental research has gone on for centuries, and it continues as vigorously today as it ever has. In fact, in the last decade, the controversy has intensified, making animal testing a topic at the highest level of debate of any socioscientific issue in the United States. This book presents all sides of the issue so that readers can come to their own conclusions as to the morality and validity of animal experimentation, and provides biographies of individuals and descriptions of organizations that have been involved in the debate over the centuries. Additionally, it documents the historical shift in thinking that made animal experimentation commonplace between the time of the ancient Greeks and the 19th century, to the mindset of some who argue for an end to the practice and alternative ways of conducting medical experimentation to benefit human health. Presents an introduction to the history of scientific research utilizing animals and a thorough review of current issues relating to animal experimentation Provides perspectives in which stakeholders in the field outline and explain their personal views on animal testing Supplies an extensive annotated bibliography of books, articles, reports, and online resources Includes profiles of important individuals and organizations Provides an outstanding resource for secondary school students, undergraduates, or general readers with an interest in medical and biological research or animal welfare

This combination manual and downloadable resources provide much-needed training on the proper handling of rats used in biomedical research. The downloadable resources include narrated video clips that demonstrate and describe each procedural technique. The manual contains handouts with color illustrations and descriptive text for each technique, including the purpose and application of the procedure, recommended skills, and necessary supplies. It can be used as a training resource and refresher for lab animal veterinarians, veterinary technicians, animal care staff, trainers, and research investigators and staff who work with rats.

During the past decade as the data on gene sequences and expression patterns rapidly accumulated, cell-free protein synthesis technology has also experienced a revolution, becoming a powerful tool for the preparation of proteins for their functional and structural analysis. In Cell-Free Protein Production: Methods and Protocols, experts in the field contribute detailed techniques, the uses of which expand deep into the studies of biochemistry, molecular biology, and biotechnology. Beginning briefly with basic methods and historical aspects, the book continues with thorough coverage of protein preparation methods, the preparation of proteins that are generally difficult to prepare in their functional forms, applications of the cell-free technologies to protein engineering, as well as some methods that are expected to constitute a part of future technologies. Written in the highly successful Methods in Molecular Biology series format, the chapters include 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 cutting-edge, Cell-Free Protein Production: Methods and Protocols aims to help researchers continue the growth of the vital exploration of cell-free sciences and technologies in order to better understand the dynamic lives of cells.