This revised third edition has been updated to cover all aspects of chiral drugs from the academic, governmental industrial and clinical perspective reflecting the many advances in techniques and methodology. The title will cover new material including the use of enzymes for the synthesis and resolution of enantiomeric compounds as well, as their use in drug discovery; how stereochemistry impacts on decisions taken during the ADMET (absorption, distribution, metabolism, excretion, toxicity) stage of drug discovery; issues faced during the final stages of the drug development process; the impact of ICH (International Conference on Harmonisation) on the use of single isomer drugs; racemic switches; and legal perspectives looking at IP and patent issues surrounding chiral switches and marketing single enantiomer switches.

This Third Edition comprehensively presents all aspects of chiral drugs from scientific, academic, governmental, industrial, and clinical points of view. This one-stop text covers the lifespan of stereochemistry, from its early history, including an overview of terms and concepts, to the current drug development process, legal and regulatory issues, and the new stereoisomeric drugs.

New topics include:

• The use of enzymes in the synthesis and resolution of enantiometrically pure compounds in drug discovery
• How stereochemistry impacts decisions made in the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) stages of drug discovery
• A chapter on pharmacokinetics and pharmacodynamics that discusses the issues faced during the final stages of the drug development process
• The impact of International Conference on Harmonisation on the use of single isomer drugs
• Chiral switches
• The concept of molecular chiral recognition and how it affects the separation and behavior of stereochemically pure drugs
• A chapter on the legal perspectives of patent issues surrounding chiral switches and the marketing of single enantiomer switches
• This will be a one-stop shop for pharmaceutical scientists and chemists working with chiral drug molecules
  

Led by both children s rights perspectives and methodological arguments, there is an increasing emphasis on children and young people s participation in health and social care research by researchers, policy makers and funding bodies with many now considering the active involvement of children and young people a requirement. There is little exploration of how to address and overcome the many challenges arising from their participation, however.

Divided into five parts, this practical book begins by considering what research with young people is and why we should do it, before leading the reader into how to undertake it. The book then provides practical examples of action and finishes with reflections about the whole process. Bringing together a variety of experienced researchers, from a wide range of backgrounds in health and social care and including young people, the chapters provide insight for practical action, as well as critical and theoretical reflection. Involving Children and Young People in Health and Social Care Research includes issues on:

• Understanding the reasons and processes for involving children and young people in research
• Making sure that involvement is meaningful and not merely tokenistic
• Developing research methods that are commensurate with different ages and abilities
• Ensuring adequate training and preparation, for children, young people and adults to make involvement meaningful
• Power and relationships between young people researchers and adult researchers
• Sustaining young people s interest and motivation
• Addressing ethical issues that arise throughout the research journey

Committed to partnership and participation throughout the entire process of the active involvement of children and young people in health and social care research, this text provides invaluable insights and is a resource for all those conducting research in and with children and young people.

The 2e of the gold standard text in the field, "Nonhuman Primates in Biomedical Research" provides a comprehensive, up-to-date review of the use of nonhuman primates in biomedical research. The "Biology and Management" volume provides basic information on the natural biology of nonhuman primates and the current state of knowledge regarding captive management. Each chapter contains an extensive list of bibliographic references, photographs, and graphic illustrations to provide the reader with a thorough review of the subject.
Now in four color throughout, making the book more visually stimulating to enhance learning and ease of useFully revised and updated, providing researchers with the most comprehensive review of the use of nonhuman primates in biomedical researchAddresses commonly used nonhuman primate biomedical models, providing researchers with species-specific information

Drug Discovery and Development, Third Edition presents up-to-date scientific information for maximizing the ability of a multidisciplinary research team to discover and bring new drugs to the marketplace. It explores many scientific advances in new drug discovery and development for areas such as screening technologies, biotechnology approaches, and evaluation of efficacy and safety of drug candidates through preclinical testing. This book also greatly expands the focus on the clinical pharmacology, regulatory, and business aspects of bringing new drugs to the market and offers coverage of essential topics for companies involved in drug development. Historical perspectives and predicted trends are also provided. Features: Highlights emerging scientific fields relevant to drug discovery such as the microbiome, nanotechnology, and cancer immunotherapy; and novel research tools such as CRISPR and DNA-encoded libraries Case study detailing the discovery of the anti-cancer drug, lorlatinib Venture capitalist commentary on trends and best practices in drug discovery and development Comprehensive review of regulations and their impact on drug development, highlighting special populations, orphan drugs, and pharmaceutical compounding Multidiscipline functioning of an Academic Research Enterprise, plus a chapter on Ethical Concerns in Research Contributions by 70+ experts from industry and academia specialists who developed and are practitioners of the science and business

Medicinal Chemistry: A Look at How Drugs Are Discovered is written for those who are interested in learning how drugs are discovered. Compared to other books on the market, this text takes a different approach by presenting the subject on chemical reaction mechanism terms, which ideally makes the subject matter more interesting and easier to comprehend. The authors describe the drug discovery process, from advancing an initial lead to the approval process, and include drug discovery sources. Additional features: Explains medicinal chemistry on chemical mechanism terms, allowing for a more interesting and easier to comprehend text Includes valuable insights toward the various pathways taken at pharmaceutical industries in drug discoveries Improved by including questions raised and suggestions made from students in the authors' medicinal chemistry classes This book will benefit both upper level undergraduates and graduates studying in the fields of medicinal chemistry and drug discovery, as well as scientists working in the pharmaceutical industry.

The Minipig in Biomedical Research is a comprehensive resource for research scientists on the potential and use of the minipig in basic and applied biomedical research, and the development of drugs and chemicals. Written by acknowledged experts in the field, and drawing on the authors global contacts and experience with regulatory authorities and the pharmaceutical and other industries, this accessible manual ranges widely over the biological, scientific, and practical uses of the minipig in the laboratory. Its coverage extends from the minipig s origins, anatomy, genetics, immunology, and physiology to its welfare, health, and husbandry; practical dosing and examination procedures; surgical techniques; and all areas of toxicity testing and the uses of the minipig as a disease model. Regulatory aspects of its use are considered.

The reader will find an extensive amount of theoretical and practical information in the pharmacology; ADME and toxicology chapters which will help scientists and managers when deciding which species to use in basic research; drug discovery and pharmacology; and toxicology studies of chemicals, biotechnology products and devices. The book discusses regulatory uses of minipigs in the evaluation of human and veterinary pharmaceuticals, medical devices, and other classes of xenobiotics. It describes features of normal health, normal laboratory values, and common diseases. It also carefully elucidates ethical and legal considerations in their supply, housing, and transport. The result is an all-inclusive and up to date manual about the experimental uses of the minipig that describes How to and Why and What to expect in the normal, combining enthusiasm and experience with critical assessment of its values and potential problems."

This book provides an introduction to the principles of both cardiovascular epidemiology and molecular pathophysiology; as a unique aspect, it also outlines and discusses the molecular concepts underlying epidemiological observations. This second volume is focused on all aspects concerning "secondary risk factors" in terms of diseases associated with enhanced risk for cardiovascular events. The book promotes the use of interdisciplinary approaches in the field of preventive medicine based on recent advances in molecular and cellular pathophysiology. The book offers a valuable resource for researchers in basic biomedical fields and clinical scientists alike, as well as guidelines for novel avenues of research in both basic pathophysiology and cardiovascular therapy and prevention.

The main focus of this book is on brown adipose tissue and its metabolic function. The book provides a timely update on the latest research and shows where the field is heading. Brown adipose tissue (BAT) dissipates energy and has received considerable attention in the last few years, having been re-discovered in adult humans in 2007/9. Moreover, BAT might offer a target for novel therapies to address obesity, a health condition that has reached pandemic dimensions.

With new statistical and scientific issues arising in adaptive clinical trial design, including the U.S. FDA's recent draft guidance, a new edition of one of the first books on the topic is needed. Adaptive Design Methods in Clinical Trials, Second Edition reflects recent developments and regulatory positions on the use of adaptive designs in clinical trials. It unifies the vast and continuously growing literature and research activities on regulatory requirements, scientific and practical issues, and statistical methodology. New to the Second EditionAlong with revisions throughout the text, this edition significantly updates the chapters on protocol amendment and clinical trial simulation to incorporate the latest changes. It also includes five entirely new chapters on two-stage adaptive design, biomarker adaptive trials, target clinical trials, sample size and power estimation, and regulatory perspectives. Following in the tradition of its acclaimed predecessor, this second edition continues to offer an up-to-date resource for clinical scientists and researchers in academia, regulatory agencies, and the pharmaceutical industry. Written in an intuitive style at a basic mathematical and statistical level, the book maintains its practical approach with an emphasis on concepts via numerous examples and illustrations.

The authoritative source on clinical data management Extensively revised and updated, with the addition of new chapters and authors, this long-awaited second edition covers all aspects of clinical data management. Giving details of the efficient clinical data management procedures required to satisfy both corporate objectives and quality audits by regulatory authorities, this text will be a timely publication in an ever-changing field. The volume:

• Is written by well-known and experienced authors in this area
• Provides new approaches to major topics in clinical data management
• Contains new chapters on systems software validation, database design and performance measures

The purpose of this book is to provide an overview of the biology of the planorbid snail Biomphalaria glabrata mainly as related to the snail 's role as a host of larval trematodes . This snail is of great importance in medical and economic zoology as a vector of important trematode (fluke) diseases in human and veterinary medicine and in wildlife biology. Moreover, this snail is a useful model for numerous basic studies in biology and chemistry. A book that provides modern coverage of diverse topics from the molecule to the community of this snail as related to larval trematode parasitism is not available. This book should appeal to a wide audience of biologists, ecologists, biochemists, malacologists, parasitologists, public health workers, epidemiologists, and graduate and advanced undergraduate students in biomedical and allied health sciences.

The new 4th edition of Histopathology of Preclinical Toxicity Studies is now completely in full color and continues to describe the pathology found in drug safety studies in laboratory animals with an evidence-based discussion of the relevance of these findings to the clinical investigation of new drugs for humans. Organized according to organ systems, this revision features a thoroughly updated bibliography and discusses new drug-induced pathologies and applicable species comparisons to aid in the preclinical safety assessment of new medicines. This updated reference is essential for those involved in drug safety evaluation, including pathologists, toxicologists and pharmacologists working in corporate, government, academic and research settings.

NEW TO THE FOURTH EDITION:

*This edition is in full color and featuresnearly 200 high-quality images

*Provides extended commentary on the relevance of pathological findingsand features a fully updatedbibliography containing sources for further reading

*Includes new content coverage on the commonly used transgenic animal models that are used in safety assessment, specific tumor types induced by drugs in rodents, and new drug-induced pathologies and lesions. "

Adaptive clinical trial designs, unlike traditional fixed clinical trial designs, enable modification of studies in response to the data generated in the course of the trial. This often results in studies that are substantially faster, more efficient, and more powerful. Recent developments in web-based real-time data entry and advances in statistical methods have made adaptive clinical trials much more popular because they have become both more practical and attractive. However, there is paucity of resources that explain the mathematical framework and the practical considerations for adaptive designs without the use of highly technical statistical jargon. Suitable for readers in academia, industry, and government involved in drug development, Adaptive and Flexible Clinical Trials is the first book that comprehensively explains all essential aspects of adaptive clinical trials. Written in an easy-to-understand style aimed at clinicians and other non-statisticians, this book focuses not on the statistical details, but rather on the application of statistical concepts for adaptive clinical trials. Utilizing concrete examples, the book thoroughly explains the design, conduct, and analysis of adaptive and flexible clinical trials, allowing readers to select and design the appropriate trial designs from a conceptual perspective. From basic theory to real-life practical issues, it covers all aspects of adaptive and flexible clinical trials, including regulatory issues, interim analysis, adaptive dosing, and sequential designs.

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.

Clinical Trials in Neurology comprehensively tackles the methodology and design of clinical trials in neurological disease. A general section deals with the ethical aspects, drug development and regulatory requirements, basic trial designs and the statistics used. A diseases section tackles specific aspects of disorders, focusing on the relevant ethical issues, outcome variables and experience with large multicentre trials.

Understanding Research in Clinical and Counseling Psychology, Second Edition, is written and designed for graduate students in the psychology and counseling fields, for whom the value of psychological research is not always readily apparent. Contributed to by experts in their respective fields, this text presents research as an indispensable tool for practice, a tool that is used every day to advance knowledge and improve assessment, treatment choice, and client outcomes. The book is divided into four logical parts: Research Foundations, Research Strategies, Research Practice, and finally, Special Problems. Included is a chapter that addresses one of the most important controversies, the distinction between realistic and "gold standard" efficacy studies. The remainder of the book addresses salient issues such as conducting research in various cultures, operating an empirically-oriented practice, and performing research with families, children, and the elderly. Students and professors will find the coverage ample and penetrating, without being too overwhelming.

This book covers the broad field of cellular, molecular, preclinical, and clinical imaging either associated with or combined with photodynamic therapy (PDT). It showcases how this approach is used clinically for cancer, infections, and diseases characterized by unwanted tissue such as atherosclerosis or blindness. Because the photosensitizers are also fluorescent, the book also addresses various imaging systems such as confocal microscopy and small animal imaging systems, and highlights how they have been used to follow and optimize treatment, and to answer important mechanistic questions. Chapters also discuss how imaging has made important contributions to clinical outcomes in skin, bladder, and brain cancers, as well as in the development of theranostic agents for detection and treatment of disease. This book provides a resource for physicians and research scientists in cell biology, microscopy, optics, molecular imaging, oncology, and drug discovery.

As a result of new statistical and mathematical approaches, improved visualization tools, and recognition by international regulatory groups, quantitative structure-activity relationships (QSARs) now play important roles in pharmacology for the design of new drugs as well as in toxicology and ecotoxicology for hazard identification and risk assessment. Providing up-to-date coverage of the field, Three Dimensional QSAR: Applications in Pharmacology and Toxicology presents the most recent QSAR methods and illustrates their scope, advantages, and limitations. Part I The first part of the book addresses CoMFA and related methods, such as CoMSIA, FLUFF, SOMFA. It also describes shape-, surface-, and volume-based approaches, including MSA, excluded volume, LIV, HASL, receptor surface model, COMPASS, and CoMSA. Part II Focusing on methods that use 3D information, the second part covers autocorrelation methods, such as GRIND; similarity-based methods, including similarity matrices and quantum similarity indices; and quantitative spectroscopic data-activity relationships. Some applications in data mining are also explored. Part III The third part deals with post-3D models. The authors discuss the adaptation of the receptor and simultaneous presence of several conformers or solvation mechanisms. Part IV The final part presents receptor-related approaches as well as docking and free energy calculations, which are treated at various levels. This part concerns the extensive sampling of phase space and approximate methods, such as linear interaction energy, Poisson-Boltzmann, and generalized Born models. A case study covering several parallel approaches is also developed. An appendix offers the basic principles of modeling and statistical tools routinely required in QSAR methodologies, including optimization methods, molecular mechanics and dynamics, multivariate analysis, nonlinear models, and evolutionary techniques. It provides newcomers

Fluorescence Molecular Tomography: Principles and Applications is the first book to cover the underlying principles and practical applications of fluorescence molecular tomography (FMT) in a systematic manner. Using a tutorial approach, the text begins with an overview of the fundamentals of FMT and goes on to detail image reconstruction approaches (including linear and nonlinear reconstruction algorithms), FMT instrumentations (including time-domain, frequency-domain, and continuous-wave domain systems), and implementation of image-enhancing schemes (including both software and hardware approaches). Further chapters examine multimodal approaches combining photoacoustic tomography (PAT), computed tomography (CT), single-photon emission tomography (SPECT), and magnetic resonance imaging (MRI) and discuss bioluminescence tomography and miniaturized FMT from hand-held to endoscopic FMT. A final chapter looks at clinical applications and animal studies. This authoritative and practical guide will serve as a valuable reference for researchers, scientists, clinicians, and industry professionals. The first book dedicated to fluorescence molecular tomography (FMT); Covers underlying principles and practical applications; Written by a leading FMT research pioneer and expert.

Judge Your Practices Against This Benchmark Manual COST Action B-24 established four working groups to research and discuss issues relevant to laboratory animal science. These included the housing of animals, environmental needs, refinement of procedures, genetically modified animals, and cost-benefit analysis. Based on the groups' findings, The COST Manual of Laboratory Animal Care and Use: Refinement, Reduction, and Research provides a consensual European view of best practices for individuals and institutions caring for and working with laboratory animals. What is COST? COST (European Cooperation in Science and Technology) is an intergovernmental initiative that promotes coordination of nationally funded science and research at a European level. This book focuses on reduction and refinement strategies and includes insightful contributions from 44 experts drawn from various EU countries. Addressing only the most commonly used mammalian species-rats, mice, and rabbits-each chapter of the book follows a similar structure: * Objectives outline the breadth of the chapter's coverage * Key Factors summarize the central issues that underpin good practice * Questions Unresolved close each chapter, identifying areas of uncertainty and prompting investigations directed at advancing knowledge and application within relevant fields The COST Manual of Laboratory Animal Care and Use: Refinement, Reduction, and Research is the reference sure to be found in the lab coats of those responsible for the care and welfare of animals and those overseeing and conducting activities related to the use of animals for scientific purposes.

Already popular in the analysis of medical device trials, adaptive Bayesian designs are increasingly being used in drug development for a wide variety of diseases and conditions, from Alzheimer's disease and multiple sclerosis to obesity, diabetes, hepatitis C, and HIV. Written by leading pioneers of Bayesian clinical trial designs, Bayesian Adaptive Methods for Clinical Trials explores the growing role of Bayesian thinking in the rapidly changing world of clinical trial analysis. The book first summarizes the current state of clinical trial design and analysis and introduces the main ideas and potential benefits of a Bayesian alternative. It then gives an overview of basic Bayesian methodological and computational tools needed for Bayesian clinical trials. With a focus on Bayesian designs that achieve good power and Type I error, the next chapters present Bayesian tools useful in early (Phase I) and middle (Phase II) clinical trials as well as two recent Bayesian adaptive Phase II studies: the BATTLE and ISPY-2 trials. In the following chapter on late (Phase III) studies, the authors emphasize modern adaptive methods and seamless Phase II-III trials for maximizing information usage and minimizing trial duration. They also describe a case study of a recently approved medical device to treat atrial fibrillation. The concluding chapter covers key special topics, such as the proper use of historical data, equivalence studies, and subgroup analysis. For readers involved in clinical trials research, this book significantly updates and expands their statistical toolkits. The authors provide many detailed examples drawing on real data sets. The R and WinBUGS codes used throughout are available on supporting websites. Scott Berry talks about the book on the CRC Press YouTube Channel.

This fully updated edition provides selected mouse genetic techniques and their application in modeling varieties of human diseases. The chapters are mainly focused on the generation of different transgenic mice to accomplish the manipulation of genes of interest, tracing cell lineages, and modeling human diseases. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Mouse Genetics: Methods and Protocols, Second Edition delivers fundamental techniques and protocols to geneticists, molecular biologists, cell and developmental biologists, students, and postdoctoral fellows working in the various disciplines of genetics, developmental biology, mouse genetics, and modeling human diseases.

The concept of frailty offers a convenient way to introduce unobserved heterogeneity and associations into models for survival data. In its simplest form, frailty is an unobserved random proportionality factor that modifies the hazard function of an individual or a group of related individuals. Frailty Models in Survival Analysis presents a comprehensive overview of the fundamental approaches in the area of frailty models. The book extensively explores how univariate frailty models can represent unobserved heterogeneity. It also emphasizes correlated frailty models as extensions of univariate and shared frailty models. The author analyzes similarities and differences between frailty and copula models; discusses problems related to frailty models, such as tests for homogeneity; and describes parametric and semiparametric models using both frequentist and Bayesian approaches. He also shows how to apply the models to real data using the statistical packages of R, SAS, and Stata. The appendix provides the technical mathematical results used throughout. Written in nontechnical terms accessible to nonspecialists, this book explains the basic ideas in frailty modeling and statistical techniques, with a focus on real-world data application and interpretation of the results. By applying several models to the same data, it allows for the comparison of their advantages and limitations under varying model assumptions. The book also employs simulations to analyze the finite sample size performance of the models.

This book discusses the fundamental concepts of the green synthesis of nanoparticles and presents the latest advances in this emerging field. Providing a comprehensive overview of developments related to nanoparticle synthesis using fungi, algae, bryophytes, pteridophytes, gymnosperms, monocotyledons, dicotyledonous (angiosperms) and animal systems, it also explores techniques for the characterization of these nanoparticles. Lastly, it reviews the applications and toxicity of biologically synthesized green nanoparticles. Given its scope, it is a valuable resource for students, researchers and policymakers working in the field of nanobiotechnology and nanoscience.

The practice of medicine is both learned and advanced through the compilation and study of cases -- vignettes that record the presentation, diagnosis, and treatment of individual patients and diseases. This is especially true of psychosomatic medicine (PSM), which depends on the "compelling case" to distill clinical knowledge and communicate it to students, residents, and clinicians. An invaluable contribution to the field, the Casebook of Psychosomatic Medicine describes the psychiatric symptoms and/or illnesses managed by the PSM psychiatrist in collaboration with other medical colleagues. The book presents a broad range of cases illustrating the medical, psychosocial, and intertwined situations psychiatrists are likely to encounter in an academic medical center setting.

No other single volume offers a broader range of engaging, detailed, and nuanced PSM cases, or grounds them so firmly in a psychiatric, psychosocial, and spiritual context. Here are just a few of this patient-centered book's most impressive and useful features: - The relevant science underlying each case is addressed in discussion sections, allowing the book to be read as a stand-alone volume. Alternatively, the cases can be read as instructive and insightful illustrations by the reader who has already absorbed the fundamentals of PSM from standard textbooks in the field.- This user-friendly book is organized by the organ system or disease type of the presenting illness or symptom.- Content rare in volumes of this kind includes detailed coverage of the diagnosis and management of cognitive disorders; the management of drug toxicity states; determinations of decisional capacity for medical decision making; and "stress and adaptation," an issue the PSM psychiatrist encounters daily.- The authors strongly believe that one of the most crucial roles for the psychiatrist is in the medical center, and the book reflects that orientation. - The book addresses the importance of understanding the impact of patients' systemic illnesses on their psychiatric symptoms, and modifying interventions and care accordingly. These abilities are critical to sound PSM practice.

Although PSM has a long and noble history, it is the newest of the psychiatric subspecialties, and as the literature expands, more and more clinicians will incorporate PSM treatment modalities into their practice. The Casebook of Psychosomatic Medicine is an essential contribution to that body of knowledge and establishes a new standard with which to face the future of this exciting field.