Using time-to-event analysis methodology requires careful definition of the event, censored observation, provision of adequate follow-up, number of events, and independence or "noninformativeness" of the censoring mechanisms relative to the event. Design and Analysis of Clinical Trials with Time-to-Event Endpoints provides a thorough presentation of the design, monitoring, analysis, and interpretation of clinical trials in which time-to-event is of critical interest. After reviewing time-to-event endpoint methodology, clinical trial issues, and the design and monitoring of clinical trials, the book focuses on inferential analysis methods, including parametric, semiparametric, categorical, and Bayesian methods; an alternative to the Cox model for small samples; and estimation and testing for change in hazard. It then presents descriptive and graphical methods useful in the analysis of time-to-event endpoints. The next several chapters explore a variety of clinical trials, from analgesic, antibiotic, and antiviral trials to cardiovascular and cancer prevention, prostate cancer, astrocytoma brain tumor, and chronic myelogonous leukemia trials. The book then covers areas of drug development, medical practice, and safety assessment. It concludes with the design and analysis of clinical trials of animals required by the FDA for new drug applications. Drawing on the expert contributors' experiences working in biomedical research and clinical drug development, this comprehensive resource covers an array of time-to-event methods and explores an assortment of real-world applications.

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.

A considerable number of journal publications using a range of qualitative synthesis approaches has been published. Mary Dixon-Woods and colleagues (Mary Dixon-Woods, Booth, & Sutton, 2007) identified 42 qualitative evidence synthesis papers published in health care literature between 1990 and 2004. An ongoing update by Hannes and Macaitis (2010)identified around 100 additional qualitative or mixed methods syntheses. Yet these generally lack a clear, detailed description of what was done and why (Greenhalgh et al, 2007; McInnes & Wimpenny, 2008). Choices are most commonly influenced by what others have successfully used in the past or by a particular school of thought (Atkins et al, 2008; Britten et al, 2002). This is a substantive limitation. This book brings balance to the options available to researchers, including approaches that have not had a substantial uptake among researchers. It provides arguments for when and why researchers or other parties of interest should opt for a certain approach to synthesis, which challenges they might face in adopting it and what the potential strengths and weaknesses are compared with other approaches. This book acts as a resource for readers who would otherwise have to piece together the methodology from a range of journal articles. In addition, it should stimulate further development and documentation of synthesis methodology in a field that is characterized by diversity.

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."

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.

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.

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.

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.

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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The definitive guide to CBPR concepts and practice, updated and expanded Community-Based Participatory Research for Health: Advancing Health and Social Equity provides a comprehensive reference for this rapidly growing field in participatory and community-engaged research. Hailed as effective by the Centers for Disease Control and Prevention, CBPR and CEnR represent the link between researchers and community and lead to improved public health outcomes. This book provides practitioner-focused guidance on CBPR and CEnR to help public health professionals, students, and practitioners from multiple other clinical, planning, education, social work, and social science fields to successfully work towards social and health equity. With a majority of new chapters, the book provides a thorough overview of CBPR history, theories of action and participatory research, emerging trends of knowledge democracy, and promising practices. Drawn from a ten-year research effort, this new material is organized around the CBPR Conceptual Model, illustrating the importance of social context, promising partnering practices, and the added value of community and other stakeholder engagement for intervention development and research design. Partnership evaluation, measures, and outcomes are highlighted, with a revised section on policy outcomes, including global health case studies. For the first time, this updated edition also includes access to the companion website, featuring lecture slides of conceptual and partnership evaluation-focused chapters, with resources from appendices to help bring CBPR concepts and practices directly into the classroom. Proven effective year after year, CBPR has become a critically important framework for public health, and this book provides clear reference for all aspects of the practice. Readers will: Examine the latest research on CPBR, and incorporate new insights into practice Understand the history and theoretical basis of CPBR, and why it has been so effective Reflect on critical issues of racism, power, and privilege; trust development; ethical practice within and beyond IRBs; and cultural humility Learn new partnership evaluation and collective reflection strategies, including measures and metrics, to enhance their own practice for improved health and social equity outcomes

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

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.

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.

A natural long-chain polymer, chitin is the main component of the cell walls of fungi, the exoskeletons of arthropods (including crustaceans and insects), the radulas of mollusks, and the beaks and internal shells of cephalopods. However, marine crustacean shells are the primary sources of the chitin derivative chitosan. Chitin and chitosan are useful for various biological and biomedical applications, although they have been limited by poor solubility in the past. Current research focuses on increasing their solubility and bioactivity through molecular modifications. The resulting derivatives are receiving much attention for interesting properties, such as biocompatibility, biodegradability, and nontoxicity, that make them suitable for use in the biomedical field. Chitin and Chitosan Derivatives: Advances in Drug Discovery and Developments presents current research trends in the synthesis of chitin and chitosan derivatives, their biological activities, and their biomedical applications. Part I discusses basic information about the synthesis and characterization of a variety of derivatives, including the preparation of chitin nanofibers. Part II covers chitin and chitosan modifications as the basis for biological applications. It describes antioxidant, anti-inflammatory, anticancer, antiviral, anticoagulant, and antimicrobial activities. Part III addresses chemically modified and composite materials of chitin and chitosan derivatives for biomedical applications, such as tissue engineering, nanomedicine, drug delivery, and wound dressing. A must-have reference for novices and experts in biotechnology, natural products, materials science, nutraceuticals, and biomedical engineering, this book presents a wide range of biological and biomedical applications of chitin and chitosan derivatives for drug discovery and development.

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.

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.

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.

This fresh addition to the rapidly expanding Springer series on stem cells represents an additional forward step in our understanding of the causes, diagnosis, and cell-related therapies of major human diseases as well as debilitating injuries to human tissue and organs. Showcasing the work of more than 80 contributors from 13 nations, it offers an unrivalled breadth of differing perspectives on the subject, with dedicated sections covering umbilical cord, induced pluripotent, embryonic, and hematopoietic stem cells, in addition to stem cells in tumors and cancer, and the applications of stem cells in regenerative medicine. Enhanced by numerous color illustrations and tables that provide graphic clarification and summaries of key results, the volume succeeds in bringing together research results from oncologists, neurosurgeons, physicians, research scientists, and pathologists, whose accumulated wealth of practical experience will inform and inspire further developments in the vital and urgent work of cancer diagnosis, cure, and prevention.

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.

Each year thousands of biomedical and behavioral researchers submit grant applications to the United States Public Health Service (USPHS) for support of their research or research training activities. The majority of these applications are submitted to the National Institutes of Health (NIH). By describing the inner workings of the NIH extramural programs and providing practical information about grant programs and processes, this authoritative work is designed to help investigators gain a more favorable edge in obtaining support for their research proposals. It offers practical insights into a broad spectrum of the basic and clinical research interests of the 21 NIH research granting components, and identifies the various mechanisms of support. Descriptions, guidance, and advice are also provided on specific areas including: how to prepare a grant application, the peer review system, the procedures leading to award decisions, the responsibilities of the NIH staff in managing the review and referral of applications, and managing grant programs. Other extramural policies and procedures are covered such as the appeals system, animal welfare, the privacy act, and research involving human subjects. Legislation, funding, and the NIH budget are also discussed. Written by two former senior-level managers at the National Institutes of Health and current consultants to several USPHS agencies, A Guide to NIH Grant Programs is a valuable reference source for members of the biomedical and behavioral research community.

This book is a comprehensive guide on neural stem cell behavior in health and disease. The book confers the altered behavior of endogenous neural stem cells in neurodegenerative disease conditions and the prospects of neural stem cell therapy for alleviating brain dysfunction in a variety of neurodegenerative disorders.Neural stem cell activity and neurogenesis in the adult brain is now confirmed in virtually all mammalian species including humans. Hence, a series of chapters in the first half of the book discusses the current knowledge on mechanisms of neural stem cell activity, the extent and functional significance of neurogenesis in the adult brain under normal, aged and disease environments, the susceptibility of neural stem cells and the plasticity of neurogenesis to alcohol, drugs of abuse and anesthetic agents, and advanced techniques that trigger neurogenesis in non-neurogenic regions.A second series of chapters in this book are focused on discussing the promise and efficacy of grafting of neural stem cells and/or other stem cells for treating neurological disorders such as Parkinson's disease, stroke, temporal lobe epilepsy, Alzheimer's disease and spinal cord injury. The final chapter confers on advances that are made in manufacturing a variety of neural cell types from human pluripotent stem cells that can be used as donor cells for cell transplantation.

Science today makes progress through the imaginative harvesting of knowledge g- erated by the many, rather than as the result of the isolated endeavours of the lone researcher. Innovations in the physical sciences from the development of nuclear te- nologies to the laser, have involved research teams working collectively. Collabo- tion is the rule rather than the exception. In the social sciences this model is all but reversed. Here it is not uncommon to encounter the solitary enthusiast, relishing an independence of spirit and pursuing their own private research agenda. All the more surprising then that a group of researchers from several different disciplines, should have come together in the late 1980s with nothing more substantial on the agenda than that they share their thoughts on the topic of measuring the value of health, or more specifically, on the way that the value of health might vary across different countries. Few scientific enterprises can have begun as cautiously or uncertainly. Few can have developed a cohesion and dynamism that lasted decades and continues to drive ahead after long years of scientific endeavour. Such is the good fortune that befell those of us who came together to form what was later to be known as the Euro- Qol Group. The Group's creation is principally due to the shared professional asso- ation of its members with one man, an economist by training and a visionary academic by inclination and temperament - Alan Williams.

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.

Squamous cell carcinoma of the esophagus has a lower incidence than other gastrointestinal tract cancer; however, there are many difficult issued related to the choice of appropriate therapy for these patients. In recent years, the use of multimodal treatment has greatly improved the prognosis of patients affected by this disease but several aspects of the oncological and surgical management are still controversial. This book aims to give a homogeneous approach to esophageal cancer treatment, based on the author's lifetime experience in conjunction with exhaustive review of recent literature. In each chapter surgeons and oncologists will find appropriate tools for correct management of the diagnosis and therapy of this difficult disease. The book analyzes all the aspects of staging and treatment, such as modern diagnostic and staging techniques (MRI or PET-CT), endoscopic treatment of early cancer, new minimally invasive and open surgical techniques, and combined treatment. In addition, there are chapters dedicated to the postoperative course of these patients, as well as their quality of life, with indications for the correct follow-up and treatment of relapses.