Is adaptive randomization always better than traditional fixed-schedule randomization? Which procedures should be used and under which circumstances? What special considerations are required for adaptive randomized trials? What kind of statistical inference should be used to achieve valid and unbiased treatment comparisons following adaptive randomization designs? Modern Adaptive Randomized Clinical Trials: Statistical and Practical Aspects answers these questions and more. From novel designs to cutting-edge applications, this book presents several new and key developments in adaptive randomization. It also offers a fresh and critical look at a number of already-classical topics. Featuring contributions from statisticians, clinical trialists, and subject-matter experts in academia and the pharmaceutical industry, the text: Clarifies the taxonomy of the concept of adaptive randomization Discusses restricted, covariate-adaptive, response-adaptive, and covariate-adjusted response-adaptive (CARA) randomization designs, as well as randomized designs with treatment selection Gives an exposition to many novel adaptive randomization techniques such as brick tunnel randomization, targeted least absolute shrinkage and selection operator (LASSO)-based CARA randomization, multi-arm multi-stage (MAMS) designs, to name a few Addresses the issues of statistical inference following covariate-adaptive and response-adaptive randomization designs Describes a successful implementation of a single pivotal phase II/III adaptive trial in infants with proliferating hemangioma Explores some practical aspects of phase II dose-ranging studies and examines statistical monitoring and interim analysis issues in response-adaptive randomized clinical trials Modern Adaptive Randomized Clinical Trials: Statistical and Practical Aspects covers a wide spectrum of topics related to adaptive randomization designs in contemporary clinical trials. The book provides a thorough exploration of the merits of adaptive randomization and aids in identifying when it is appropriate to apply such designs in practice.

In Silico Drug Discovery and Design: Theory, Methods, Challenges, and Applications provides a comprehensive, unified, and in-depth overview of the current methodological strategies in computer-aided drug discovery and design. Its main aims are to introduce the theoretical framework and algorithms, discuss the range of validity, strengths and limitations of each methodology, and present applications to real world problems in the drug discovery arena. Special emphasis has been given to the emerging and most pressing methodological challenges in in silico drug discovery and design. The book assumes a basic knowledge of physical principles and molecular modeling. Particular attention has been paid to outline the underlying physico-chemical foundation of the methods described, thus providing the necessary background to avoid a "black-box" approach. In each self-contained chapter, this is presented together with the latest developments and applications, and the challenges that lie ahead. Assembling a unique team of experts to weigh in on the most important issues influencing modern computational drug discovery and design, this book constitutes both a desktop reference to academic and industrial researchers in the field, and a textbook for students in the area of molecular modeling and drug discovery. Comprised of 18 chapters and divided into three parts, this book: Provides a comprehensive, unified, and in-depth overview of the current methodological strategies in computer-aided drug discovery and design Outlines the underlying physico-chemical foundation of the methods described Presents several applications of computational methods to real world problems in the drug design field Helps to avoid a "black-box" approach to in silico drug discovery Constitutes an actual textbook for students in the area of molecular modeling and drug discovery Gives the reader the adequate background to face the current challenges of the field In Silico Drug Discovery and Design: Theory, Methods, Challenges, and Applications describes the theoretical framework, methods, practical applications and case examples relevant to computer-aided drug lead discovery and design. This text will surely aid in understanding the underlying physical foundation of computational tools and their range of application, thus facilitating the interpretation of simulation results.

The use of human tissue for medical research and scientific progress raises many ethical and legal challenges. The procurement, storage and transfer of human tissue for research purposes have posed significant questions over recent years, and a number of high profile scandals in the UK prompted the publication of the Madden Report on Post Mortem Practice and Procedures in Irish hospitals in 2006. Additionally, tissue-related research tends to be most promising if samples and information are shared across national borders, but the heterogeneity of current rules and guidelines within the member states of the European Union calls all the more for clarification.
This multi-authored interdisciplinary text, edited by four experienced researchers, explores many of the issues concerning biobank-related research and aims to provide answers to the most urgent questions by means of ethical, philosophical, and legal investigation. It provides a fascinating insight into a wide range of interlinking research perspectives and serves as a comprehensive reference to the state of play ethically and legally in Europe. It will be of value to medics and social scientists, human tissue researchers, and policy makers who have an interest in ethical and legal issues of human tissue research.

A complete guide to understanding cluster randomised trials Written by two researchers with extensive experience in the field, this book presents a complete guide to the design, analysis and reporting of cluster randomised trials. It spans a wide range of applications: trials in developing countries, trials in primary care, trials in the health services. A key feature is the use of R code and code from other popular packages to plan and analyse cluster trials, using data from actual trials. The book contains clear technical descriptions of the models used, and considers in detail the ethics involved in such trials and the problems in planning them. For readers and students who do not intend to run a trial but wish to be a critical reader of the literature, there are sections on the CONSORT statement, and exercises in reading published trials. * Written in a clear, accessible style * Features real examples taken from the authors extensive practitioner experience of designing and analysing clinical trials * Demonstrates the use of R, Stata and SPSS for statistical analysis * Includes computer code so the reader can replicate all the analyses * Discusses neglected areas such as ethics and practical issues in running cluster randomised trials How to Design, Analyse and Report Cluster Randomised Trials in Medicine and Health Related Research provides an excellent reference tool and can be read with profit by statisticians, health services researchers, systematic reviewers and critical readers of cluster randomised trials.

Key Features: 1. Describes the development of the randomized, controlled trial as the gold standard of proof. 2. Unravels the meaning of "randomized," "double-blind" and "p-values" in a simplified manner for students and clinicians. 3. Contains timeless information on how medical evidence can be understood.

Molecular and Cellular Basis of Metastasis: Road to Therapy, the latest in the Advances in Cancer Research series, provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics, with this volume covering the molecular and cellular basis of metastasis.

How to identify optimal phase II trial designs Providing a practical guide containing the information needed to make crucial decisions regarding phase II trial designs, A Practical Guide to Designing Phase II Trials in Oncology sets forth specific points for consideration between the statistician and clinician when designing a phase II trial, including issues such as how the treatment works, choice of outcome measure and randomization, and considering both academic and industry perspectives. A comprehensive and systematic library of available phase II trial designs is included, saving time otherwise spent considering multiple manuscripts, and real-life practical examples of using this approach to design phase II trials in cancer are given. A Practical Guide to Designing Phase II Trials in Oncology: * Offers a structured and practical approach to phase II trial design. * Considers trial design from both an academic and industry perspective. * Includes a structured library of available phase II trial designs. * Is relevant to both clinical and statistical researchers at all levels * Includes real life examples of applying this approach. * For those new to trial design, A Practical Guide to Designing Phase II Trials in Oncology will be a unique and practical learning tool, providing an introduction to the concepts behind informed decision making in phase II trials. For more experienced practitioners, the book will offer an overview of new, less familiar approaches to phase II trial design, providing alternative options to those which they may have previously used.

This new edition explores and provides an update on the biology and pathogenesis of human cytomegalovirus infection. Modern techniques that are currently being utilized to investigate the molecular aspects of viral infection, as well as how these new research studies are leading to new approaches to mitigate disease, are also provided. Given the key role the virus plays in significant acute and chronic human disease in all stages of life, from newborns to seniors, the need for clear methodologies to further explore the biology of HCMV infection and mitigation strategies is readily apparent. Written in the highly successful Methods in Molecular Biology 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 up-to-date, Human Cytomegaloviruses: Methods and Protocols, Second Edition serves as an ideal scientific reference for basic and clinical scientists and medical personnel on the modern understanding of the pathobiology of the virus, and the approaches, techniques, and models to study human cytomegalovirus infection and disease.

This volume looks at major clinical trials for motor and non-motor symptoms in Parkinson's Disease (PD) and covers important aspects, including trial design, sample selection, and outcome selection. Chapters in this book discuss topics such as toxin-based rodent or genetic models of PD; clinical trials for motor symptoms, L-DOPA related motor complications, and gait disorders; clinical trials for mood disorders, troubled sleep, autonomic dysfunction; and clinical trials for disease modifying therapies. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory or research center. Cutting-edge and authoritative, Clinical Trials in Parkinson's Disease is a valuable resource for clinicians and researchers who want to enhance their interpretation of results from clinical trials and to design their own high-quality trials.

Accurate sample size calculation ensures that clinical studies have adequate power to detect clinically meaningful effects. This results in the efficient use of resources and avoids exposing a disproportionate number of patients to experimental treatments caused by an overpowered study. Sample Size Calculations for Clustered and Longitudinal Outcomes in Clinical Research explains how to determine sample size for studies with correlated outcomes, which are widely implemented in medical, epidemiological, and behavioral studies. The book focuses on issues specific to the two types of correlated outcomes: longitudinal and clustered. For clustered studies, the authors provide sample size formulas that accommodate variable cluster sizes and within-cluster correlation. For longitudinal studies, they present sample size formulas to account for within-subject correlation among repeated measurements and various missing data patterns. For multiple levels of clustering, the level at which to perform randomization actually becomes a design parameter. The authors show how this can greatly impact trial administration, analysis, and sample size requirement. Addressing the overarching theme of sample size determination for correlated outcomes, this book provides a useful resource for biostatisticians, clinical investigators, epidemiologists, and social scientists whose research involves trials with correlated outcomes. Each chapter is self-contained so readers can explore topics relevant to their research projects without having to refer to other chapters.

Patient organizations and social health movements offer one of the most important and illuminating examples of civil society engagement and participation in scientific research and research politics. Influencing the research agenda, and initiating, funding and accelerating the development of diagnostic tools, effective therapies and appropriate health-care for their area of interest, they may champion alternative, sometimes controversial, programs or critique dominant medical paradigms. Some movements and organizations advocate for medical recognition of contested illnesses, as with fibromyalgia orADHD, while some attempt to "de-medicalize" others, such as obesity or autism. Bringing together an international selection of leading scholars and representatives from patients' organizations, this comprehensive collection explores the interaction between civil society groups and biomedical science, technology development, and research politics. It takes stock of the key findings of the research conducted in the field over the past two decades and addresses emerging problems and future challenges concerning the interrelations between health movements and patient organisations on the one hand, and biomedical research and research policies on the other hand. Combining empirical case studies with conceptual discussion, the book discusses how public participation can contribute to, as well as restrict, the democratization of scientific knowledge production. This volume is an important reference for academics and researchers with an interest in the sociology of health and illness, science and technology studies, the sociology of knowledge, medical ethics or healthcare management and research, as well as medical researchers and those involved with health-related civil society organizations.

Today, when many parents seem reluctant to have their children vaccinated, even with long proven medications, the Salk vaccine trial, which enrolled millions of healthy children to test an unproven medical intervention, seems nothing short of astonishing. In Selling Science, medical historian Stephen E. Mawdsley recounts the untold story of the first large clinical trial to control polio using healthy children - 55,000 healthy children - revealing how this long-forgotten incident cleared the path for Salk's later trial. Mawdsley describes how, in the early 1950s, Dr. William Hammon and the National Foundation for Infantile Paralysis launched a pioneering medical experiment on a previously untried scale. Conducted on over 55,000 healthy children in Texas, Utah, Iowa, and Nebraska, this landmark study assessed the safety and effectiveness of a blood component, gamma globulin, to prevent paralytic polio. The value of the proposed experiment was questioned by many prominent health professionals as it harbored potential health risks, but as Mawdsley points out, compromise and coercion moved it forward. And though the trial returned dubious results, it was presented to the public as a triumph and used to justify a federally sanctioned mass immunization study on thousands of families between 1953 and 1954. Indeed, the concept, conduct, and outcome of the GG study were sold to health professionals, medical researchers, and the public at each stage. At a time when most Americans trusted scientists, their mutual encounter under the auspices of conquering disease was shaped by politics, marketing, and at times, deception. Drawing on oral history interviews, medical journals, newspapers, meeting minutes, and private institutional records, Selling Science sheds light on the ethics of scientific conduct, and on the power of marketing to shape public opinion about medical experimentation.

This collection provides detailed information on current advances in analytical methods and strategies employed for monitoring and discovering a wide range of novel psychoactive substances (NPS) in clinical and forensic laboratories. The main classes of NPS in terms of prevalence include synthetic cannabinoids, synthetic cathinones, synthetic opioids, and designer or synthetic benzodiazepines, and this book explores selecting the appropriate sample matrix and analytical testing approaches for laboratories faced with NPS drug testing, such as in blood, urine, saliva, and hair. Written for the Methods in Pharmacology and Toxicology series, chapters in this volume feature the kind of detailed implementation advice from the experts that leads to successful results in the lab. Authoritative and practical, Methods for Novel Psychoactive Substance Analysis serves as an ideal guide for forensic and clinical toxicologists, pharmacologists and chemists in academic and research settings, as well as for private laboratories seeking to increase our ability to test for these substances. @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-536869121 1107305727 33554432 0 415 0;}@font-face {font-family:Calibri; panose-1:2 15 5 2 2 2 4 3 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-469750017 -1073732485 9 0 511 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:11.0pt; font-family:"Times New Roman",serif; mso-fareast-font-family:Calibri; mso-fareast-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi; mso-ansi-language:EN-US; mso-fareast-language:EN-US;}.MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; mso-bidi-font-size:11.0pt; mso-fareast-font-family:Calibri; mso-fareast-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi; mso-ansi-language:EN-US; mso-fareast-language:EN-US;}div.WordSection1 {page:WordSection1;}

The four sections of this book cover cell and molecular biology of tumor metabolism, metabolites, tumor microenvironment, diagnostics and epigenetics. Written by international experts, it provides a thorough insight into and understanding of tumor cell metabolism and its role in tumor biology. The book is intended for scientists in cancer cell and molecular biology, scientists in drug and diagnostic development, as well as for clinicians and oncologists.

This is the only book to offer an evidence-based model for retaining students and ensuring success across the nursing education spectrum. It is designed to assist faculty in creating, implementing, and evaluating student retention and academic success strategies. This model, Nursing Undergraduate Retention and Success (NURS), can be used effectively with all kinds of nursing programs, both traditional and nontraditional, including diploma, ADN, RN-BS, and accelerated BS.

The book features the "Nursing Student Retention Toolkit," an easy-to-use digital toolkit for assessment and planning that is thoroughly cross-referenced and integrated into the text. Together, these complementary resources offer a wide selection of educational activities and support strategies for diverse learners and settings. The text provides guidelines for maximizing educational strengths, identifying and assessing at-risk students, facilitating student retention, and revitalizing teaching methods. It examines the multidimensional factors that must be considered, including cultural values and beliefs, and describes proven strategies for promoting retention and academic success such as faculty advisement, promoting professional events and membership, peer partnerships, and enrichment programs. "Nursing Student Retention," with its breadth of information and one-of-a-kind digital toolkit, will be of great value to nurse educators, administrators, and graduate students. This new edition features:

An easy-to-use format that includes the "Nursing Student Retention Toolkit, "a digital adjunct containing assessment tools, and templates for designing, implementing, and evaluating retention strategies Chapters updated to provide a wealth of new information and evidence-based strategies Real-life scenarios featuring diverse learners and settings Vignettes to synthesize and demonstrate application of learning

Increase in antibiotic resistance has forced researchers to develop new drugs against microorganisms. Lipopeptides are produced as secondary metabolites by some microorganisms. Computer-aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates provides the identification of novel ligands for different antimicrobial lipopeptides. Along with identification, it also provides some of the in silico drug design processes, namely homology modelling, molecular docking, QSAR studies, drug ADMET studies and pharmacophore studies to check the ligand-lipopeptide interaction. Some lipopeptides have shown anti-cancerous properties too, and this book discusses the required templates to design new drugs using computational techniques. Key Features: Focuses on the use lipopeptides as new antimicrobial compounds Presents the basics of in silico modelling for design and development of new drug molecules, and is therefore of interest to beginners in the field Provides a step-by-step process for identification of drug molecules and testing its efficacy in silico Couples with courses on patents and intellectual property rights

Defines best practices for leveraging of discovery research to facilitate a science-based, rational, and predictive preclinical development program to ensure clinical efficacy and safety Includes general principles, animal models, biomarkers, preclinical toxicology testing paradigms, and practical applications

Palliative care is rapidly evolving as a multidimensional therapeutic model devoted to improving the quality of life of all patients with life-threatening illness. Symptom control, management of psychosocial and spiritual concerns, decision making consistent with values and goals, and care of the imminently dying that is appropriate and sensitive to the unique needs of the individual and family - these are among the critical issues addressed through palliative care. As this discipline has evolved, the need for research in all these areas has become widely acknowledged. Issues in Palliative Care Research describes both the progress that already has been made in the investigation of these issues and the methodological elements that must be addressed in future studies. The perspective is broad and the overriding goal is to inform about the state of the art in these rapidly evolving areas of research.

The detailed volume aims to provide a comprehensive hands-on manual covering all the techniques involved in the cellular and molecular identification and characterization of both normal hematopoietic and leukemic stem cells, both from human patients and from mouse models of human leukemia. The book also covers the most frequently used experimental approaches for the generation of such stem cell-based models of human leukemia. 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 comprehensive, Leukemia Stem Cells: Methods and Protocols serves as an ideal guide for researchers, both expert and novice, seeking to further our knowledge of this vital avenue of cancer research.

Respiration is an area of the medical study that undergoes fast developments. A better understanding of the neural and cellular mechanisms underlying respiratory disorders and lung function is essential for the evidence-based pharmacotherapy and for optimizing the patient care and prophylactic measures to improve the health and quality of life. This comprehensive book is a blend of basic and clinical research. The book is thought to promote the translation of science into clinical practice. The book presents an update on the areas of current research and clinical interest in the neurobiology of the respiratory system. Recent innovations in detection and management of respiratory diseases are described. The book will be a base of reference in the field of respiration for years to come and a source of future research ideas. This book is a required text for respiratory scientists, neuropathologists, and for clinicians searching for 'bench to bedside' treatments of lung diseases.

Reliably optimizing a new treatment in humans is a critical first step in clinical evaluation since choosing a suboptimal dose or schedule may lead to failure in later trials. At the same time, if promising preclinical results do not translate into a real treatment advance, it is important to determine this quickly and terminate the clinical evaluation process to avoid wasting resources. Bayesian Designs for Phase I-II Clinical Trials describes how phase I-II designs can serve as a bridge or protective barrier between preclinical studies and large confirmatory clinical trials. It illustrates many of the severe drawbacks with conventional methods used for early-phase clinical trials and presents numerous Bayesian designs for human clinical trials of new experimental treatment regimes. Written by research leaders from the University of Texas MD Anderson Cancer Center, this book shows how Bayesian designs for early-phase clinical trials can explore, refine, and optimize new experimental treatments. It emphasizes the importance of basing decisions on both efficacy and toxicity.

Because of the huge potential of human embryonic stem (hES) cells, especially the newly developed human induced pluripotent stem (hiPS) cells, in disease treatment and life quality improvement, enormous efforts have been made to develop new methodologies to translate lab discoveries in stem cell research into bed-side clinical technologies. In Human Embryonic and Induced Pluripotent Stem Cells: Lineage-Specific Differentiation Protocols, experts in the field present a comprehensive collection of protocols designed for labs around the world. The topics covered in this detailed volume include techniques used for maintenance of hES and iPS cells in either small or large scale, techniques for directing hES and iPS cell lineage specification, techniques for enhancing the maturity of differentiated hES and iPS cells within three-dimensional scaffolds, techniques for reprogramming adult cells into iPS cells, techniques for generating patient-specific iPS cells, and techniques for translating hES and iPS cell research into new therapies. Chapters include lab ready protocols with tips on troubleshooting and avoiding known pitfalls. Wide-ranging and authoritative, Human Embryonic and Induced Pluripotent Stem Cells: Lineage-Specific Differentiation Protocols will be a tremendous aid for researchers and students who wish to explore these areas and transform their discoveries into the next generation of regenerative medicine and tissue engineering technologies.

This book summarizes the state-of-the art in the development of T cell-based "in vitro" assays, which offer useful tools for hazard identification, risk assessment and improvement of diagnostics. It will be of interest to scientists, the chemical and pharmaceutical industry, and regulators involved in the replacement of animal testing methods.

The identification of hazardous chemicals and drugs is essential to ensuring human health. The ban on animal testing for the cosmetics industry since 2009 and international efforts to reduce and replace animal testing in research and immunotoxicology call for alternative "in vitro" methods. The most specific immune response to chemicals and drugs that cause allergic contact dermatitis, respiratory disease and adverse drug reactions is the highly antigen-specific T lymphocyte response. Therefore the use of T cells as tools for identifying contact allergens and drugs that may cause health problems is of great interest.

Lead 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. However, although increasingly important, there is little exploration of how to address and overcome the many challenges arising from their participation. 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 knowledge base in the domains of quality of life, well-being, and subjective well-being is continuing to grow at a rapid rate. In light of this growth, and the interest it reflects on the part of scholars, practitioners, and policy makers internationally, this book will play an important role in bringing scholars and students up to date on diverse topics and promoting and encouraging research in the field of quality-of-life (QOL) studies. Unlike most other similar publications quality of life studies is broadly construed to involve all of the social and health sciences. This volume has much to offer the reader. The papers reflect a diversity of disciplinary and methodological perspectives, it contains material on (a) the monitoring, assessing, and modelling of quality of life, (b) matters of policy, finance, marketing, and business, and (c) papers devoted to the determinants and correlates of well-being and quality of life.