Discover the Latest Statistical Approaches for Modeling Exposure-Response Relationships Written by an applied statistician with extensive practical experience in drug development, Exposure-Response Modeling: Methods and Practical Implementation explores a wide range of topics in exposure-response modeling, from traditional pharmacokinetic-pharmacodynamic (PKPD) modeling to other areas in drug development and beyond. It incorporates numerous examples and software programs for implementing novel methods. The book describes using measurement error models to treat sequential modeling, fitting models with exposure and response driven by complex dynamics, and survival analysis with dynamic exposure history. It also covers Bayesian analysis and model-based Bayesian decision analysis, causal inference to eliminate confounding biases, and exposure-response modeling with response-dependent dose/treatment adjustments (dynamic treatment regimes) for personalized medicine and treatment adaptation. Many examples illustrate the use of exposure-response modeling in experimental toxicology, clinical pharmacology, epidemiology, and drug safety. Some examples demonstrate how to solve practical problems while others help with understanding concepts and evaluating the performance of new methods. The provided SAS and R codes enable readers to test the approaches in their own scenarios. Although application oriented, this book also gives a systematic treatment of concepts and methodology. Applied statisticians and modelers can find details on how to implement new approaches. Researchers can find topics for or applications of their work. In addition, students can see how complicated methodology and models are applied to practical situations.

This book reaches out to a wide variety of professionals in the biomedical field with an interest in inflammatory bowel disease (IBD). Enormous progress has been made in the last few years since the publication of the first edition in the study of complex diseases and IBD, with hundreds of genomic regions identified that are associated with increased risk. Authored by leading clinical and research scientists in the field, the book includes state-of-the art synopses of recent genetic findings, and their interpretation for current and future exploitation in translational approaches to personalized medicine in IBD. The book also covers risk prediction, improved diagnostic and therapeutic precision, dissection of disease phenotypes and subtypes, identification of biomarkers, and host gene-microbiota interactions of clinical relevance.

Overuse has become a major issue of healthcare quality, safety, and sustainability around the world. In this Element, the authors discuss concepts, terminology, and the history of concerns. They show how interventions to address overuse target multiple drivers. They highlight successes and promising approaches, but also challenges in generating and using evidence about overuse. They emphasise that different stakeholder perceptions of value must be recognised. System-level efforts to restrict access to services have created tensions between stakeholder groups and stimulated politicised debates about rationing. They argue for clear articulation of priorities, problem definition, mechanisms for interventions, and areas of uncertainty. Policy-makers should prioritise transparency, be alert to inequalities as they seek to reduce overuse, and consider how to balance controlling use with enabling clinicians to respond to individual circumstances. The complexity of the drivers and possible solutions to overuse require the use of multiple research methods, including social science studies. This title is also available as Open Access on Cambridge Core.

How do we know whether a particular treatment really works? How reliable is the evidence? And how do we ensure that research into medical treatments best meets the needs of patients? These are just a few of the questions addressed in a lively and informative way in Testing Treatments. Brimming with vivid examples, Testing Treatments will inspire both patients and professionals. Building on the success of the first edition, Testing Treatments has now been extensively revised and updated. The Second Edition includes a thought-provoking chapter on screening, explaining why early diagnosis is not always better. Other new chapters explore how over-regulation of research can work against the best interests of patients, and how robust evidence from research can be drawn together to shape the practice of healthcare in ways that allow treatment decisions to be reached jointly by patients and clinicians. Testing Treatments urges everyone to get involved in improving current research and future treatment, and outlines practical steps that patients and doctors can take together.

The field of stem cell biology is expanding with a continued surge of new information related to its applications. Over past few years, stem cells have been extensively used in cell therapy, tissue engineering, in vitro drug testing among others. At the moment there is no single book available which comprehensively describes the significance of various application of stem cells derived from embryonic and adult sources from lab to clinics. In this edited volume, we discuss basics and advanced topics of stem cells to help researchers, students and professional find the most important information in a single source of updated information about stem cells and relevant applications. This book is divided in 12 chapters and covers topics such as in vitro cell culture, 3D cell culture, cell therapy, tissue engineering, cell factory, cell functionality, in vitro drug testing, organ development, autologous transplantation, allogeneic transplantation, adult stem cells, multipotent stem cells, induced pluripotent stem cells, a pluripotent and embryonic stem cells.

Take Your NI Trial to the Next Level Reflecting the vast research on noninferiority (NI) designs from the past 15 years, Noninferiority Testing in Clinical Trials: Issues and Challenges explains how to choose the NI margin as a small fraction of the therapeutic effect of the active control in a clinical trial. Requiring no prior knowledge of NI testing, the book is easily accessible to both statisticians and nonstatisticians involved in drug development. With over 20 years of experience in this area, the author introduces the basic elements of the NI trials one at a time in a logical order. He discusses issues with estimating the effect size based on historical placebo control trials of the active control. The book covers fundamental concepts related to NI trials, such as assay sensitivity, constancy assumption, discounting, and preservation. It also describes patient populations, three-arm trials, and the equivalence of three or more groups.

The great hurry to realise promised cures in stem cell research requires regulation to guarantee bioethical research practices. Yet, increasingly similar national guidelines for stem cell research yields a range of diverging research practices. This book shows how the different rationale of regulation affects stem cell research practices in Asia. In low- and medium income countries such as India and China the advancement of science has a different weight on the national agenda, and the evaluation of scientific research is measured with a different yardstick, depending on the political and national research environment. For developing countries the question of research funding into stem cell research, healthcare, and the donation of embryos, foetuses and oocytes entail different considerations compared to in affluent welfare societies. Moreover, research institutions have different cultural and political histories, so that the meaning of formal guidelines, legislation and social rules may differ according to their various institutional settings. This volume discusses the informal cultures, social conventions and traditions that are crucial to the way in which stem cell research takes place in Asia. This book was originally published as a special issue of New Genetics and Society.

Neuropsychiatric disorders such as schizophrenia, mood disorders, Alzheimer s disease, epilepsy, alcoholism, substance abuse and others are some of the most debilitating illnesses worldwide characterizing by the complexity of the causes, and lacking the laboratory tests that may promote diagnostic and prognostic procedures. Recent advances in neuroscience, genomic, genetic, proteomic and metabolomic knowledge and technologies have opened the way to searching biomarkers and endophenotypes, which may offer powerful and exciting opportunity to understand the etiology and the underlying pathophysiological mechanisms of neuropsychiatric disorders. The challenge now is to translate these advances into meaningful diagnostic and therapeutic advances.

This book offers a broad synthesis of the current knowledge about diverse topics of the biomarker and endophenotype strategies in neuropsychiatry. The book is organized into four interconnected volumes: Neuropsychological Endophenotypes and Biomarkers (with overview of methodological issues of the biomarker and endophenotype approaches in neuropsychiatry and some technological advances), Neuroanatomical and Neuroimaging Endophenotypes and Biomarkers, Metabolic and Peripheral Biomarkers and Molecular Genetic and Genomic Markers . The contributors are internationally and nationally recognized researchers and experts from 16 countries.

This four-volume handbook is intended for a broad spectrum of readers including neuroscientists, psychiatrists, neurologists, endocrinologists, pharmacologists, clinical psychologists, general practitioners, geriatricians, health care providers in the field of neurology and mental health interested in trends that have crystallized in the last decade, and trends that can be expected to further evolve in the coming years. It is hoped that this book will also be a useful resource for the teaching of psychiatry, neurology, psychology and mental health."

EQ-5D from the EuroQol Group is a standardised, non-disease-specific instrument for describing and valuing health. It is in widespread use in many countries and has been applied in many different settings. EQ-5D is now an integral feature of many clinical trials and is increasingly used in population health surveys.

This book reports on the results of the European Union-funded EQ-net project which furthered the development of EQ-5D in the key areas of valuation, application and translation. The primary effort concentrated on harmonising and integrating the results of the various EuroQol valuation projects. Most importantly, the book includes a set of VAS-based preference weights for all the EQ-5D health states based on cross-European EQ-5D data.

This book provides the most comprehensive account to date of the EuroQol Group endeavour. It will appeal to clinicians, nurses, health services researchers, health economists, those responsible for audit and quality assurance, public health specialists and managers in health care institutions, and the pharmaceutical industry.

Whilst the health sciences are a broad and diverse area, and includes public health, primary care, health psychology, psychiatry and epidemiology, the research methods and data analysis skills required to analyse them are very similar. Moreover, the ability to "appraise" and "conduct" research is emphasised within the health sciences and students are expected increasingly to do both. "

Introduction to Research Methods and Data Analysis in the Health Sciences" presents a balanced blend of quantitative research methods, and the most widely used techniques for collecting and analysing data in the health sciences. Highly practical in nature, the book guides you, step-by-step, through the research process, and covers both the consumption and the production of research and data analysis. Divided into the three strands that run throughout quantitative health science research critical numbers, critical appraisal of existing research, and conducting new research this accessible textbook introduces:

• Descriptive statistics
• Measures of association for categorical and continuous outcomes
• Confounding, effect modification, mediation and causal inference
• Critical appraisal
• Searching the literature
• Randomised controlled trials
• Cohort studies
• Case-control studies
• Research ethics and data management
• Dissemination and publication
• Linear regression for continuous outcomes
• Logistic regression for categorical outcomes.

A dedicated companion website offers additional teaching and learning resources for students and lecturers, including screenshots, R programming code, and extensive self-assessment material linked to the book s exercises and activities.

Clear and accessible with a comprehensive coverage to equip the reader with an understanding of the research process and the practical skills they need to collect and analyse data, it is essential reading for all undergraduate and postgraduate students in the health and medical sciences.

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Stem Cells reviews the current knowledge on stem cell science covering all its major topics, from basic cell biology to legislation. Volume II concentrates on mechanisms of stem cell regeneration in the adult organism with the aim to understand how lost tissue can be replaced during adulthood and aging. The second focus of this volume is on stem cell identification and manipulation, including applications in basic research, medicine, and industry. Volume II closes with an outlook on generalized approaches to solve legislative and ethical challenges.

Acacias: The Genus Acacia (sensu lato) is an evidence-based treatment of this super genus, through the eyes of a clinical pharmacognosist and integrative medicine specialist. The book begins with antiviral activity, revealing within the five genera of Acacia s.l., pharmacological properties and pharmacologically active compounds. Profiles of prominent species within these genera, including photographs, accompany the narrative of current research and traditional usage into antibacterial, antifungal, anticancer, antidiabetic, metabolic syndrome ameliorative, and psychotherapeutic potential. Features: Comprehensive treatment of the entire Acacia sensu lato genus. Aids ethnopharmacological prospectors of new sources of novel botanically-based medicines for modern metabolic and psychiatric diseases. Illuminates the presence of psychedelic simple substituted tryptamines in trees and their medical and psychotherapeutic potential. Acacias: The Genus Acacia (sensu lato) provides a unique and comprehensive coverage of one of the most interesting and diverse genera of trees, firmly entrenched in the Levant, Africa, Australia, the Far East, and the New World. The influence of these genera on pharmacy and industry (especially through gum arabic, wildcrafted in Africa from Senigallia senigallia), human consciousness, the advent and development of religions, planetary ecology, botanical therapeutics, and the emergence of psychedelic medicine reflects both the history of our species and the transformative promise of tomorrow.

The discovery of the two inherited susceptibility genes BRCA1 and BRCA2 in the mid-1990s created the possibility of predictive genetic testing and led to the establishment of specific medical programmes for those at high risk of developing breast cancer in the UK, US and Europe. The book provides a coherent structure for examining the diversity of practices and discourses that surround developments linked to BRCA genetics, and to the evolving field of genetics more broadly. It will be of interest to students and scholars of anthropology, sociology, history of science, STS, public health and bioethics. Chapter 8 of this book is freely available as a downloadable Open Access PDF under a Creative Commons Attribution-Non Commercial-No Derivatives 3.0 license. https://s3-us-west-2.amazonaws.com/tandfbis/rt-files/docs/Open+Access+Chapters/9780415824064_oachapter8.pdf

This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 1 focuses on the biology of autophagy, including the signaling pathways, regulating processes and biological functions. Autophagy is a fundamental physiological process in eukaryotic cells. It not only regulates normal cellular homeostasis, and organ development and function, but also plays an important role in the pathogenesis of a wide range of human diseases. Thanks to the rapid development of molecular biology and omic technologies, research on autophagy has boomed in recent decades, and more and more cellular and animal models and state-of the-art technologies are being used to shed light on the complexity of signaling networks involved in the autophagic process. Further, its involvement in biological functions and the pathogenesis of various diseases has attracted increased attention around the globe. Presenting cutting-edge knowledge, this book series is a useful reference resource for researchers and clinicians who are working on or interested in autophagy.

Learn how to evaluate and apply health sciences research with this beginner's guide! Reading Research: A User-Friendly Guide for Health Professionals, 7th Edition provides a clear introduction to reading and understanding research articles, with practical guidelines for implementing research into clinical practice. It describes how to interpret common research methods including qualitative, quantitative and mixed-method approaches, and explains how to find relevant, reliable research on the internet. Written by Barbara Davies and Jo Logan, both of whom are noted educators and research experts, this easy-to-use pocket guide is ideal for both students and health professionals. Concise overview of health sciences-related research maximizes your study time and makes it easier to understand qualitative, quantitative, and mixed-methods research. Succinct introduction to reading and understanding health sciences research articles is accompanied by practice worksheets and other learning resources on an Evolve website. Helpful guidelines suggest how to find interesting research results, identify how to use research results towards planning and delivering best practices and improving patient outcomes, and recommend actions to address barriers to using research in practice. UNIQUE! Tips boxes provide practical, easy-to-follow advice for those who are new to the subject. UNIQUE! Alert! boxes warn of common assumptions made when reading research. Recommendations for best practices in research include brief definitions of popular research terms as well as links to World Health Organization information, the latest RNAO (Registered Nurses' Association of Ontario) Best Practice Guidelines, and guidelines from Australia, the USA, the UK, and other countries. NEW! Enhanced worksheet exercises on the Evolve website demonstrate how to apply knowledge gained from the text, based on research articles drawn from Australia, Canada, Europe, and the USA, on a variety of health issues encountered in hospital and community settings.

Randomised Response-Adaptive Designs in Clinical Trials presents methods for the randomised allocation of treatments to patients in sequential clinical trials. Emphasizing the practical application of clinical trial designs, the book is designed for medical and applied statisticians, clinicians, and statisticians in training.

After introducing clinical trials in drug development, the authors assess a simple adaptive design for binary responses without covariates. They discuss randomisation and covariate balance in normally distributed responses and cover many important response-adaptive designs for binary responses. The book then develops response-adaptive designs for continuous and longitudinal responses, optimum designs with covariates, and response-adaptive designs with covariates. It also covers response-adaptive designs that are derived by optimising an objective function subject to constraints on the variance of estimated parametric functions. The concluding chapter explores future directions in the development of adaptive designs.

Presenting an area of research that intersects with and integrates diverse disciplines, including genomics, epigenetics, proteomics, and cellular biology, among others, Formalin-Fixed Paraffin-Embedded Tissues: Methods and Protocols collects contributions from expert researchers in order to provide practical guidelines to this complex study. Compiled in order to provide researchers with up-to-date methodological information pertaining to the utilization of genomic, transcriptomic, and proteomic data in diagnosis, prognosis, and tailored therapy, the ultimate aim of this volume is to decipher diseases at a molecular level. Divided into multiple convenient chapters, this detailed book covers various techniques to construct and utilize tissue arrays, it also provides detailed protocols in immunohistochemistry, immunofluorescence, fluorescent and chromogenic in situ hybridization, and ultimately introduces protocols for FFPET microdissection and nucleic acids extraction for their utilization in advanced techniques such as microarray CGH, DNA methylation and pyrosequencing. The volume also discusses FFPET research from an ethical standpoint and concludes with a chapter on novel tissue fixative. 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, Formalin-Fixed Paraffin-Embedded Tissues: Methods and Protocols serves as a practical guide for scientists of all backgrounds and aims to convey the appropriate sense of fascination associated with this vital field of research.

The use of human beings as research subjects poses distinctive ethical issues. Subjects of medical research are exposed to risks of harm for the sake of generating scientific knowledge that can benefit future patients and society. Ethical analysis of the challenges posed by research involving human subjects requires careful attention to the contextual details of scientific experimentation. This book contains 22 essays by Franklin G. Miller on research ethics written over a 15-year period. With the exception of the first essay, all have been previously published in bioethics and medical journals. The book is arranged into four parts. Part One addresses a general ethical perspective on the protection of human subjects in clinical research, including paternalism in research regulation and acceptable limits to research risks. The essays in Part Two examine ethical issues in study design. It includes ethical analyses of controversial types of medical experimentation-studies that provoke psychiatric symptoms, induce infections, provide patients with placebos that withhold proven effective treatments or administer fake invasive procedures, test experimental treatments in cancer patients who have exhausted all standard treatment options, and employ the use of deception to generate scientifically valid data. Part Three offers a systematic critique of "the therapeutic orientation" to clinical trials and the principle of clinical equipoise, which is widely regarded as a fundamental norm for randomized treatment studies. Part Four takes up a range of ethical issues relating to informed consent for research participation, including examination of "the therapeutic misconception" and presentation of a novel approach to the validity of consent: "the fair transaction model." An abiding theme, developed in many of the essays is that the ethics of clinical research is importantly different from the ethics of medical care.

This volume contains the Proceedings of the XVIIth ISAC Meeting held in Valladolid, Spain, July 1-5, 2008. As such, it contains the most permanent records of the combined efforts of all attendants. The meeting was held at the School of Medicine of Valladolid, that had the privilege of a recent celebration. The celeb- tion was none other than its 600th anniversary, implying that all participants were surrounded by historical landmarks, from the historical building of the University, to the Museum of polychrome sculpture of Valladolid, to the Monastery of Clarisas in Tordesillas, to the beauty and charm of Salamanca. In this ambience we had three days of intense work, distributed in several oral sessions, preceded by plenary lectures given by our invited speakers who were kind enough to provide us with the latestprogressintheirspeci c elds. We also hadtimeallottedtoposterviewing. As regularattendantsto the XVIIth ISACMeeting, we want to expressourappreciation forthevaluablediscussionssurroundingeachposter,theenthusiasticpresentationof data, the comments of colleagues with suggestions for improvement, and the plans for collaborations that emerged from these discussions. Needless to say that XVIIth ISAC Meeting was the fruit of many collabo- tive efforts. The Local Organizing Committee pro ted from the advice of several colleagues from around the world, namely, Prof. Chris Peers from Leeds, UK, Prof. Prem Kumar from Birmingham, UK, Prof. Nanduri Prabhakar from Chicago, USA, Prof. Colin Nurse from Hamilton, Canada, and Prof. Rodrigo Iturriaga from Santiago, Chile.

In cancer research, a traditional phase II trial is designed as a single-arm trial that compares the experimental therapy to a historical control. This simple trial design has led to several adverse issues, including increased false positivity of phase II trial results and negative phase III trials. To rectify these problems, oncologists and biostatisticians have begun to use a randomized phase II trial that compares an experimental therapy with a prospective control therapy. Randomized Phase II Cancer Clinical Trials explains how to properly select and accurately use diverse statistical methods for designing and analyzing phase II trials. The author first reviews the statistical methods for single-arm phase II trials since some methodologies for randomized phase II trials stem from single-arm phase II trials and many phase II cancer clinical trials still use single-arm designs. The book then presents methods for randomized phase II trials and describes statistical methods for both single-arm and randomized phase II trials. Although the text focuses on phase II cancer clinical trials, the statistical methods covered can also be used (with minor modifications) in phase II trials for other diseases and in phase III cancer clinical trials. Suitable for cancer clinicians and biostatisticians, this book shows how randomized phase II trials with a prospective control resolve the shortcomings of traditional single-arm phase II trials. It provides readers with numerous statistical design and analysis methods for randomized phase II trials in oncology.

Research in pharmacy practice and medicines use is an important component of many postgraduate and undergraduate pharmacy programmes. It is seen as invaluable in informing professional practice and service development. This clear and concise handbook considers the stages of the research process in logical order, from planning of the project through to dissemination of the findings. Divided into three comprehensive sections, contents include: i) preparation, planning and management; ii) scientific enquiry and research methodology; iii) writing up and dissemination of the findings. This third edition of Conducting Your Pharmacy Practice Research Project has been restructured to aid navigation and comprehensively revised and expanded in recognition of the increased diversity of projects undertaken by students. This systematic guide will be of use to undergraduate and postgraduate pharmacy students and their supervisors. It will also appeal to researchers unfamiliar with health services research methods and to practising pharmacists new to conducting a research project.

This volume provides protocols for mouse models of allergic diseases and guidelines for choosing a particular strains, allergen, adjuvant, and route of sensitization. Chapters detail types of allergic disease, methods that are frequently employed to analyze pathophysiology of allergic diseases, manipulation of intestinal microbiota, and desensitization of immure responses in animal models. 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. Authoritative and cutting-edge, Animal Models of Allergic Disease: Methods and Protocols aims to offer a comprehensive collection of protocols and experience-derived instructions to further allergic disease research.

The Human Hypothalamus: Neuroendocrine Disorders, Volume 181 in the Handbook of Clinical Neurology series, provides comprehensive summaries of recent research on the brain and nervous system as they relate to clinical neurology. This volume summarizes the role of the hypothalamus in neuroendocrine disorders, identifying the mechanism of action, disorder etiology, and best practices for assessment and treatment. Disorders covered include pituitary hypothalamic disorders of development and growth, hypothalamic tumor related disorders, hypothalamic autoimmune disorders and infection, disorders of vasopressin, water and sodium homeostasis, eating disorders, and gonadotropic hormone regulation disorders.

Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Consequently, the current strategies for treatment and management of patients are limited in their efficacy. The mechanisms of tissue protection and repair are probably even less understood. One reason for these limitations is the enormous complexity of the disease and every facet of its pathogenesis, the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy of treatments and their side effects. The aim of this book is to review the most recent advances made in this highly complex field.

Precision Medicine in Neurodegenerative Disorders, Part Two, Volume 193 deals with the "How" in the reconfiguration of our approach to slow the progression of those suffering from diseases of accelerated brain aging. This second Handbook of Clinical Neurology volume offers a rethinking of the animal models on which therapies are tested; outlines the progress and expected changes in biological subtyping efforts using lysosomal, endosomal, mitochondrial, immune dysregulation, and inflammatory mechanisms of disease pathophysiology; and the growing role of microbiome in shaping disease and as a future target of therapeutic efforts. The volume separates the potentially disease-modifying neurorescue and neurorestoration, (e.g., gene therapy and cell replacement therapy) from true precision medicine -matching the biology of those affected with the mechanism of the intervention of interest. Specific chapters are dedicated to the promise and challenges of extracellular vesicles for both diagnosis and treatment, the growing application of digital measures and other evaluations of clinical response, the nuts and bolts of novel adaptive clinical trial designs, and the regulatory changes needed to facilitate drug development for disease-modification purposes.