A cluster randomization trial is one in which intact social units, or clusters of individuals, are randomized to different intervention groups. Trials randomizing clusters have become particularly widespread in the evaluation of non-therapeutic interventions, including lifestyle modification, educational programmes and innovations in the provision of health care. The increasing popularity of this design among health researchers over the past two decades has led to an extensive body of methodology on the subject. This is the first book to present a systematic and united treatment of this topic; it contains distinctive chapters on the history of cluster randomized trials, ethical issues and reporting guidelines.

The Data Protection and Medical Research in Europe: PRIVIREAL series represents the results of this EC-funded project examining the implementation of Directive 95/46/EC on data protection in relation to medical research and the role of ethics committees in European countries. The series consists of five separate volumes following the complete development of the PRIVIREAL project. This volume relates to the second stage of this project and is concerned with the setting up and role of research ethics committees. It assesses their legal responsibilities, especially with regard to data protection matters and contains reports from more than 20 European countries on these issues. Focusing on the theoretical role and practical operation of research ethics committees and the impact of relevant international and national instruments, this volume will be an essential resource for all those concerned with data protection issues in medical research.

This volume is intended for neuropharmacologists, psychopharmacologists, pharmacologists, pharmacists, sleep researchers, translational neuroscience researchers, and other basic researchers and clinical scientists interested in an interdisciplinary approach to sleep medicine. The level of the book is aiming at CNS researchers, drug development scientists, basic and clinical sleep researchers, as well as senior medical students and fellows in psychiatry and neurology. Orexin and Sleep provides a unique resource, giving a comprehensive and highly readable summary of the basic concepts in orexin biology and pharmacology along with clinical applications in sleep medicine in general, and narcolepsy in particular.

Originally published in 1995, "Analysing Survival Data from Clinical Trials and Observational Studies" provides a thorough yet accessible overview of survival data analysis. It is written in a highly accessible style focussed on concepts and methods rather than theory, and includes careful explanation of the underlying statistical and medical principles. Now available in paperback, the book provides a comprehensive introduction to the subject suitable for graduate students of biostatistics and survival analysis. Provides a practical introduction to survival data analysis. Covers the core topics, including estimation of survival probabilities, as well as more advance topics, such as parametric regression models, competing risk and meta-analysis. Illustrates the methods using real data sets throughout. Written in a lucid style, suitable for students of biostatistics and survival analysis. Includes discussion of a range of software choices for applying the methods described.

"Analysing Survival Data from Clinical Trials and Observational Studies" is ideally suited to graduate students studying courses in survival analysis. The wide range of examples and applications make it an ideal practical reference for researchers and practitioners working in survival analysis from statistics, medicine and epidemiology.

Helps researchers in proteomics and oncology work together to understand, prevent, and cure cancer

Proteomic data is increasingly important to understanding the origin and progression of cancer; however, most oncologic researchers who depend on proteomics for their studies do not collect the data themselves. As a result, there is a knowledge gap between scientists, who devise proteomic techniques and collect the data, and the oncologic researchers, who are expected to interpret and apply proteomic data. Bridging the gap between proteomics and oncology research, this book explains how proteomic technology can be used to address some of the most important questions in cancer research.

"Proteomic Applications in Cancer Detection and Discovery "enables readers to understand how proteomic data is acquired and analyzed and how it is interpreted. Author Timothy Veenstra has filled the book with examples--many based on his own firsthand research experience--that clearly demonstrate the application of proteomic technology in oncology research, including the discovery of novel biomarkers for different types of cancers.

The book begins with a brief introduction to systems biology, explaining why cancer is a systems biology disease. Next, it covers such topics as: Mass spectrometry in cancer researchApplication of proteomics to global phosphorylation analysisSearch for biomarkers in biofluidsRise and fall of proteomic patterns for cancer diagnosticsEmergence of protein arraysRole of proteomics in personalized medicine

The final chapter is dedicated to the future prospects of proteomics in cancer research.

By guiding readers through the latest proteomic technologies and their applications in cancer research, "Proteomic Applications in Cancer Detection and Discovery" enhances the ability of researchers in proteomics and researchers in oncology to collaborate in order to better understand cancer and develop strategies to prevent and treat it.

Migraine is a complex neurological disorder that is characterized by a complex neurobiology, clinical features that may overlap with over 300 causes of headache, and an association with major medical illnesses and comorbid diseases. This books draws upon the authors' vast clinical experience and exhaustive knowledge of the science of migraine and the practice of headache medicine and provides this knowledge in a comprehensive yet digestible format. While migraine is often a subject in other textbooks on headache, it is the sole focus of this volume. The authors provide an up-to-date overview of the evidence base and combine this with their experience and expertise to help practitioners make informed treatment decisions. This book also provides a glimpse into the future describing new treatment modalities, including neurostimulation technologies and biologics that are emerging as potentially valuable treatment options. The authors also deal extensively with the unique and complex management of migraine in women throughout the reproductive life cycle. For those looking for a practical, insightful, and in-depth review on the subject of migraine, there is no other option.

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

The major objective of our studies in the last decade was a systematic analysis of maternal diseases during pregnancy to reveal their possible adverse effects on birth outcomes. The two most important factors of infant mortality were parti- larly analyzed: structural birth defects, known as congenital abnormalities (CAs) and preterm birth (PB). In general the objectives of scienti c studies might be either to test a new hypothesis or to con rm or confront previously published results. However, less frequently the authors/scientists have personal motivations determined by their professional activities. The authors of this book are practicing physicians and genetic epidemiologist who are mainly interested in the following three practical questions: 1. The possible adverse effects of pharmaceutical products. The possible t- atogenic potential of about 170 drugs has been evaluated very thoroughly using the data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) in the last 50 years. These drugs were used to treat maternal diseases and the ndings of our population-based case-control studies will be cited in this book and are shown in the Appendix at the end of the book. However, our long experiences showed two problems in the drug teratology. In general the evaluation of clinical doses of these drugs is a particularly dif- cult challenge due to the modi cation effects of confounders. This problem motivated one of the authors to establish a new model of disaster epidemiology.

Providing reliable information on an intervention effect, meta-analysis is a powerful statistical tool for analyzing and combining results from individual studies. Meta-Analysis of Binary Data Using Profile Likelihood focuses on the analysis and modeling of a meta-analysis with individually pooled data (MAIPD). It presents a unifying approach to modeling a treatment effect in a meta-analysis of clinical trials with binary outcomes. After illustrating the meta-analytic situation of an MAIPD with several examples, the authors introduce the profile likelihood model and extend it to cope with unobserved heterogeneity. They describe elements of log-linear modeling, ways for finding the profile maximum likelihood estimator, and alternative approaches to the profile likelihood method. The authors also discuss how to model covariate information and unobserved heterogeneity simultaneously and use the profile likelihood method to estimate odds ratios. The final chapters look at quantifying heterogeneity in an MAIPD and show how meta-analysis can be applied to the surveillance of scrapie. Containing new developments not available in the current literature, along with easy-to-follow inferences and algorithms, this book enables clinicians to efficiently analyze MAIPDs.

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

Most biological reactions and functions occur within a narrow range of pH. Any changes in the pH have great impacts on the biological functional at every level, including protein folding, enzymatic activities and proliferation and cell death. Therefore, maintain the pH homeostasis at the local or systemic level is one of the highest priorities for all multicellular organisms. Many redundant mechanisms are in place to maintain the pH homeostasis, a topic that is well covered in the scientific literature and medical textbooks. However, when the pH homeostasis is disrupted in various physiological adaptations and pathological situations, resulting acidity may trigger significant pathophysiological events and modulate disease outcomes. Therefore, understanding how various cells sense and react to acidity have broad impact in a wide variety of human diseases, including cancer, stroke, myocardial infarction and diabetes, renal and infectious diseases. In this book, many investigators have summarized the molecular genetics on the detailed mechanisms by which different mammalian cells sense and response acidity. These chapters cover the acidity with broad impact in biological understanding and human diseases and review various sensing mechanism and cellular responses to pH alterations in both physiological (taste, pain) and pathological settings (ischemia and cancers). Furthermore, these authors present a broad spectrum of investigative approaches to cellular response to acidosis in a in wide variety of human diseases.

Monoclonal antibodies have had their impact on biomedical research for more than a decade. Beside their exuberant use as reagents, quite a number of diagnostic and therapeutic approaches have been followed and an impressive number of technological improvements, e.g., humanization, recombinant miniantibodies, have been elaborated to strengthen the principle. With respect to clinical applications, the first generation of antibody 'drugs' is yielding promising results while second and third generation antibody constructs are already underway. The book reviews the status of technological development and brings this into the perspective of clinical results. A rapidly growing amount of clinical data is collected in an expanding number of indications. Hence, the review of clinical study results has been grouped according to the fields of oncology and of chronic and acute inflammation. This book will be of interest to scientists working in the fields of oncology, immunology, internal medicine and clinical chemistry.

Integrated Drug Discovery Technologies provides a global overview of emerging drug development technologies by presenting and integrating new techniques from the disciplines of chemistry, biology, and computational sciences. It combines integration of contemporary mechanization with strategies in drug delivery. Topics include: functional genomics, microfabrication techniqes, integrated proteomics technologies, high throughput screening, and fluorescence correlation spectroscopy methods.

Bayesian analyses have made important inroads in modern clinical research due, in part, to the incorporation of the traditional tools of noninformative priors as well as the modern innovations of adaptive randomization and predictive power. Presenting an introductory perspective to modern Bayesian procedures, Elementary Bayesian Biostatistics explores Bayesian principles and illustrates their application to healthcare research. Building on the basics of classic biostatistics and algebra, this easy-to-read book provides a clear overview of the subject. It focuses on the history and mathematical foundation of Bayesian procedures, before discussing their implementation in healthcare research from first principles. The author also elaborates on the current controversies between Bayesian and frequentist biostatisticians. The book concludes with recommendations for Bayesians to improve their standing in the clinical trials community. Calculus derivations are relegated to the appendices so as not to overly complicate the main text. As Bayesian methods gain more acceptance in healthcare, it is necessary for clinical scientists to understand Bayesian principles. Applying Bayesian analyses to modern healthcare research issues, this lucid introduction helps readers make the correct choices in the development of clinical research programs.

Mouse Genetics offers for the first time in a single comprehensive volume a practical guide to mouse breeding and genetics. Nearly all human genes are present in the mouse genome, making it an ideal organism for genetic analyses of both normal and abnormal aspects of human biology. Written as a convenient reference, this book provides a complete description of the laboratory mouse, the tools used in analysis, and procedures for carrying out genetic studies, along with background material and statistical information for use in ongoing data analysis. It thus serves two purposes, first to provide students with an introduction to the mouse as a model system for genetic analysis, and to give practicing scientists a detailed guide for performing breeding studies and interepreting experimental results. All topics are developed completely, with full explanations of critical concepts in genetics and molecular biology. As investigators around the world are rediscovering both the heuristic and practical value of the mouse genome, the demand for a succinct introduction to the subject has never been greater. Mouse Genetics is intended to meet the needs of this wide audience.

The meaning of Clinical Trials for humans has recently changed significantly, "evolved", so to speak. In today's environment, where ethical validity is much more strictly controlled, this meaning is far beyond "human drug testing" and much closer to the "therapeutic goal". The number of clinical trials in western countries that have perceived this change has increased rapidly and continues to increase. Although the number of clinical studies in the MENA region is increasing day by day, it is still far from its potential. Among the reasons for this are legal, technological, ethical, epidemiological, educational and economic factors. This book presents both the difficulties encountered in conducting clinical trials in MENA and suggestions for solving these difficulties.

Clinical practice guidelines were initially developed within the context of evidence-based medicine with the goal of putting medical research findings into practice. However, physicians do not always follow them, even when they seem to apply to the particular patient they have to treat. This phenomenon, known as clinical inertia, represents a significant obstacle to the efficiency of care and a major public health problem, the extent of which is demonstrated in this book. An analysis of its causes shows that it stems from a discrepancy between the objective, essentially statistical nature of evidence-based medicine on the one hand and the physician's own complex, subjective view (referred to here as "medical reason") on the other. This book proposes a critique of medical reason that may help to reconcile the principles of evidence-based medicine and individual practice. The author is a diabetologist and Professor of Endocrinology, Diabetology and Metabolic Diseases at Paris 13 University. He has authored several books, including one to be published by Springer (Philosophy and Medicine series) under the title: The Mental Mechanisms of Patient Adherence to Long Term Therapies, Mind and Care. , Diabetology and Metabolic Diseases at the Paris 13-University. He has also published Pourquoi Se soigne-t-on, Enquete sur la rationalite morale de l'observance (2007), Clinique de l'Observance, L'Exemple des diabetes (2006), and Une theorie du soin, Souci et amour face a la maladie (2010). An English adaptation of the first book is published by Springer (Philosophy and Medicine) under the title: The Mental Mechanisms of Patient Adherence to Long Term Therapies, Mind and Care.

Experimentation on animals and particularly humans is often assumed to be a uniquely modern phenomenon. But the ideas and attitudes that encourage the biological and medical sciences to experiment on living creatures date from the earliest expression of Western thought. In "Animal and Human Experimentation," Anita Guerrini looks at the history of these practices from vivisection in ancient Alexandria to present-day battles over animal rights and medical research employing human subjects.

Guerrini discusses in-depth key historical episodes in the use of living beings in science and medicine, including the discovery of blood circulation, the development of smallpox and polio vaccines, and recent AIDS research. She also explores the rise of the antivivisection movement in Victorian England, the modern animal rights movement, and current debates over gene therapy. In this highly accessible text, we learn how our understanding of an animal's capacity to feel pain has evolved. Guerrini reminds us that the ethical values of science seldom stray far from those of the society in which scientists live and work.

Ethical questions about the use of animals and humans in research remain among the most vexing within both the scientific community and society at large. These often rancorous arguments have gone on, however, with little awareness of their historical antecedents. "Animal and Human Experimentation" offers students and concerned general readers on every side of this debate a context within which to understand more fully the responsibility we all bear for the suffering inflicted on other living beings in the name of scientific knowledge.

Based upon a workshop entitled "The Small HSP World" held in Quebec 2-5 October 2014. Twenty-five scientists provided chapters for the book. The chapters are from the best scientists currently working in this field. These colleagues include Arrigo, Benesch, Benjamin, Buchner-Haslbeck-Weinkauf, Benndorf, Boelens, Carra, Chang, Currie, Ecroyd, Emanuelsson, Fu, Garrido, Golenhofen, Gusev, Hightower, Kampinga, Lavoie, MacRae, Quinlan, Tanguay, Vierling, Vigh, Weeks and Wu. Briefly, the book starts with the structure of small heat shock proteins, moving to their functions and finishing with their involvement in diseases. Although this is quite broad, the structural aspect will be the unifying theme of the book.

Omics is an emerging and exciting area in the field of science and medicine. Numerous promising developments have been elucidated using omics (including genomics, transcriptomics, epigenomics, proteomics, metabolomics, interactomics, cytomics and bioinformatics) in cancer research. The development of high-throughput technologies that permit the solution of deciphering cancer from higher dimensionality will provide a knowledge base which changes the face of cancer understanding and therapeutics.

This is the first book to provide such a comprehensive coverage of a rapidly evolving area written by leading experts in the field of omics. It complies and details cutting-edge cancer research that covers the broad advances in the field and its application from cancer-associated gene discovery to drug target validation. It also highlights the potential of using integration approach for cancer research.

This unique and timely book provides a thorough overview of developing omics, which will appeal to anyone involved in cancer research. It will be a useful reference book for graduate students of different subjects (medicine, biology, engineering, etc) and senior scientists interested in the fascinating area of advanced technologies in cancer research.

Readership: This is a precious book for all types of readers cancer researchers, oncologists, pathologists, biologists, clinical chemists, pharmacologists, pharmaceutical specialists, biostatisticians, and bioinformaticists who want to expand their knowledge in cancer research."

This book aims to set out the political, social, legal and scientific underpinning of risk assessment and risk management for toxic substances. It describes the principles and processes the practitioners undertake when looking at the regulatory risk implications of their work.

Regeneration of tissue to replace damaged or injured tissue is the goal of t- sue engineering. Biomaterials like polyglycolic acid, collagen and small-intestinal submuscosa provide a temporary scaffold to guide new tissue growth and or- nization. Typically, they need to be biodegradable, showing good cell atta- ment and proliferation and they should possess appropriate mechanical properties (Kim et al. , 2000). Synthetic polymers ful ll most of these requirements but lack cell-adhesion peptides on their surface to enhance cell attachment. Ce- adhesion peptides are present in ECM proteins like collagen and elastin. Thus a synthetic polymer coated with ECM proteins would result in a scaffold that mimics the natural cellular environment with enhanced cell attachment and p- liferation. The new bioactive scaffold will be made by combining a synthetic polymer coated with a layer of recombinant ECM proteins produced by CHO cells. The rst step consists of identifying polymers that give best results in terms of CHO cell attachment and growth. Classical techniques to determine biomass are inappropriate to evaluate 3-D structures. Thus a screening system based on stable GFP expressing CHO cells was used to compare the different scaffolds. Simple uorescent measurement after cell lysis allows determining cell attachment and p- liferation on synthetic polymers. Finally CHO cells producing human recombinant collagen I and elastin were generated. We showed that both proteins are expressed and secreted by CHO DG44 cells. 2 Materials and Methods 2.

This extensive book brings together leading melanoma researchers from across the world and highlights many of the cutting-edge protocols and experimental systems currently being used to investigate questions surrounding this disease. The volume opens with sections on 2D and 3D cell culture-based approaches for studying melanoma biology, and continues with collections of chapters examining various approaches for detecting, isolating, and characterizing circulating melanoma cells, circulating tumor DNA, and exosomes, as well as experimental procedures for studying and detecting melanoma metastasis in both pre-clinical and clinical settings, bioinformatics-based approaches, protocols for quantifying and characterizing immune cell infiltrates in both melanoma tumors and tertiary lymphoid structures, and development and evaluation of therapeutic strategies for melanoma treatment. 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 comprehensive, Melanoma: Methods and Protocols aims to serve basic research scientists and clinicians who bring questions from the clinic into the lab in order to translate observations in the laboratory into improved patient care for this highly malignant form of cancer. Chapter 14 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Assessment is arguably the most important stage of nursing. It forms the basis for any planned nursing intervention and a baseline against which subsequent events in the hospital stay can be compared. Assessment is an ongoing activity where the patient is continually reviewed and care reappraised to ensure that the patient's needs are being met. The main aim of this study is to evaluate the reliability and validity of the Byron Physical Assessment Framework (BPAF). the study involved scrutinising the BPAF to describe its purpose, conceptual basis and how it was developed. The BAF was then refined using extensive literature review and expert opinion to improve its comprehensiveness and clarity for its intended purpose. This monograph should be useful to all those attempting to construct and validate clinical assessment and measuring tools. Ruth Harris has the expertise necessary to do this in a sophisticated yet realistic way for practice colleagues.

The discovery of ER by Dr. Elwood Jensen exactly 60 years ago has not only led to the birth of a whole new vital nuclear receptor research field but also made a rapid, direct and lasting impact on the treatment and prevention of breast cancer. Since that landmark discovery, tremendous progress has been made in our understanding of the molecular functions of ER and development of targeted therapies against ER pathways for breast cancer treatment. However, there is currently no book available addressing these discoveries and recent advancement in a historical and systematic fashion. This book is intended to provide comprehensive, most up-to-date information on the history and recent advancement of ER and breast cancer by world renowned leaders in the field. These chapters include the history of the discovery of ER; physiological and pathological roles of ER; recent discovery of ER cistrome, transcriptome and its regulation of noncoding RNAs such as microRNAs and enhancer RNAs in breast cancer; development and clinical practices of the first targeted therapy Tamoxifen and other antiestrogens for breast cancer treatment; structural basis of ER and antiestrogen actions; molecular insights into endocrine resistance; the role of ER mutants, ER-beta and environmental estrogens in breast cancer; and emerging state-of-the-art therapeutic approaches currently in development to overcome treatment resistance and future perspectives. The book will provide undergraduate and graduate students, basic scientists and clinical cancer researchers, residents, fellows, as well as clinicians, oncology educators and the general public a thorough and authoritative review of these exciting topics.