Angiogenesis and lymphangiogenesis have become attractive targets for drug therapy because of their key roles in a broad spectrum of pathological disease states ranging from macular degeneration to tumor growth and metastasis. A substantial increase in the research effort over the past decade has deepened our understanding of the basic mechanisms underlying angiogenesis and lymphangiogenesis, promoting the development of promising therapeutics for the clinical management of vascular-related diseases. These extraordinary advancements have been built upon a vast array of diverse analytical techniques developed globally throughout the field. Over the years, these methods have evolved to suit the specific needs of different researchers and experimental scenarios, resulting in a myriad of technical variants of basic assay approaches.

"The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications" is an up-to-date comprehensive textbook on angiogenesis and lymphangiogenesis techniques and applications. This volume is designed to embody the collective works of experts in the clinical as well as the basic research arenas who have significantly contributed to the development and application of techniques in all areas of angiogenesis and lymphangiogenesis. Each chapter introduces and discusses one or a group of closely related techniques and convey step-by-step protocol information and detailed technical guidance to the reader. Emphasis has been placed on explanatory illustrations, critical technical steps as well as divulging information on the benefits and caveats of specific practices related to the methods discussed. This manual is intended to serve as a written guide for both newcomers and established professionals in the field.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions.This book series 'Cell Biology and Translational Medicine (CBTMED)' as part of SpringerNature's longstanding and very successful Advances in Experimental Medicine and Biology book series, has the goal to accelerate advances by timely information exchange. Emerging areas of regenerative medicine and translational aspects of stem cells are covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the tenth volume of a continuing series.

An odd and unexpected finding was reported by the laboratory of Richard Jorgensen in 1990: expression of extra copies of the gene encoding chalone synthase in petunias turned off the endogenous chalone synthase gene. An observation that appeared totally unrelated was made by the laboratory of Victor Ambrose in 1993: a gene in Caenorhabditis elegans, lin-4, controlled the timing of larval development but did not encode a protein. Rather, it expressed two small RNAs that were complementary to the 3'-untranslated region of the lin-14 gene in a region that had previously been shown to repress expression of the LIN-14 protein. From another quarter, David Baulcombe's laboratory showed in 1997 that plant viruses could induce sequen- specific gene silencing. Then in a landmark paper, Andrew Fire and Craig Mello showed in 1998 that double-stranded RNA (dsRNA) triggers a gene-silencing mechanism that they dubbed RNA interference (RNAi), for which discovery they were awarded the Nobel Prize in Physiology or Medicine in 2006. These diverse findings have triggered an explosion of research around the world in both plants and animals to discover the mechanisms and broader ramifications of RNAi. We now know that there are both exogenous pathways involving formation of siRNA when dsRNA is introduced and endogenous pathways involving miRNA, piwiRNA, and rasiRNAs. All pathways culminate in formation of an RNA-induced silencing complex (RISC) containing a member of the Argonaute protein family bound to a 22-nt RNA strand that interacts with a target mRNA or gene through Watson-Crick base pairing.

PREFACE The Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture is involved in agricultural research and development and assists Member States of FAO and IAEA in improving strategies to ensure food security through the use of nuclear techniques and related biotechnologies, where such techniques have a valuable and often unique role. In particular, molecular diagnostic methods have rapidly evolved in the past twenty years, since the advent of the Polymerase Chain Reaction (PCR). They are used in a wide range of agricultural areas such as, improving soil and water management; producing better crop varieties; diagnosing plant and animal diseases; controlling insect pests and improving food quality and safety. The uses of nucleic acid-directed methods have increased significantly in the past five years and have made important contributions to disease control country programmes for improving national and international trade. These developments include the more routine use of PCR as a diagnostic tool in veterinary diagnostic laboratories. However, there are many problems associated with the transfer and particularly, the application of this technology. These include lack of consideration of: the establishment of quality-assured procedures, the required set-up of the laboratory and the proper training of staff. This can lead to a situation where results are not assured. This book gives a comprehensive account of the practical aspects of PCR and strong consideration is given to ensure its optimal use in a laboratory environment. This includes the setting-up of a PCR laboratory; Good Laboratory Practice and standardised of PCR protocols.

Cancer is a major healthcare burden across the world and impacts not only the people diagnosed with various cancers but also their families, carers, and healthcare systems. With advances in the diagnosis and treatment, more people are diagnosed early and receive treatments for a disease where few treatments options were previously available. As a result, the survival of patients with cancer has steadily improved and, in most cases, patients who are not cured may receive multiple lines of treatment, often with financial consequences for the patients, insurers and healthcare systems. Although many books exist that address economic evaluation, Economic Evaluation of Cancer Drugs using Clinical Trial and Real World Data is the first unified text that specifically addresses the economic evaluation of cancer drugs. The authors discuss how to perform cost-effectiveness analyses while emphasising the strategic importance of designing cost-effectiveness into cancer trials and building robust economic evaluation models that have a higher chance of reimbursement if truly cost-effective. They cover the use of real-world data using cancer registries and discuss how such data can support or complement clinical trials with limited follow up. Lessons learned from failed reimbursement attempts, factors predictive of successful reimbursement and the different payer requirements across major countries including US, Australia, Canada, UK, Germany, France and Italy are also discussed. The book includes many detailed practical examples, case studies and thought-provoking exercises for use in classroom and seminar discussions. Iftekhar Khan is a medical statistician and health economist and a lead statistician at Oxford Unviersity's Center for Statistics in Medicine. Professor Khan is also a Senior Research Fellow in Health Economics at University of Warwick and is a Senior Statistical Assessor within the Licensing Division of the UK Medicine and Health Regulation Agency. Ralph Crott is a former professor in Pharmacoeconomics at the University of Montreal in Quebec, Canada and former head of the EORTC Health Economics Unit and former senior health economist at the Belgian HTA organization. Zahid Bashir has over twelve years experience working in the pharmaceutical industry in medical affairs and oncology drug development where he is involved in the design and execution of oncology clinical trials and development of reimbursement dossiers for HTA submission.

This book continues to be the definitive reference on drug metabolism with an emphasis on new scientific and regulatory developments. It has been updated based on developments that have occurred in the last 5 years, with new chapters on large molecules disposition, stereo-selectivity in drug metabolism, drug transporters and metabolic activation of drugs. Some chapters have been prepared by new authors who have emerged as subject area experts in the decade that has passed since publication of the first edition. Key Features: Continues to be the definitive reference on drug metabolism Covers the drug transporter field, disposition of protein therapeutics and metabolic activation of drugs Includes the contributions of world-class experts in their respective fields Contains the work of editors who are recognized leaders and deep content experts in the field of drug metabolism Emphasizes new scientific and regulatory developments in the field

Maintaining a practical perspective, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition explores statistics used in day-to-day clinical pharmacology work. The book is a starting point for those involved in such research and covers the methods needed to design, analyze, and interpret bioequivalence trials; explores when, how, and why these studies are performed as part of drug development; and demonstrates the methods using real world examples. Drawing on knowledge gained directly from working in the pharmaceutical industry, the authors set the stage by describing the general role of statistics. Once the foundation of clinical pharmacology drug development, regulatory applications, and the design and analysis of bioequivalence trials are established, including recent regulatory changes in design and analysis and in particular sample-size adaptation, they move on to related topics in clinical pharmacology involving the use of cross-over designs. These include, but are not limited to, safety studies in Phase I, dose-response trials, drug interaction trials, food-effect and combination trials, QTc and other pharmacodynamic equivalence trials, proof-of-concept trials, dose-proportionality trials, and vaccines trials. This second edition addresses several recent developments in the field, including new chapters on adaptive bioequivalence studies, scaled average bioequivalence testing, and vaccine trials. Purposefully designed to be instantly applicable, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition provides examples of SAS and R code so that the analyses described can be immediately implemented. The authors have made extensive use of the proc mixed procedures available in SAS.

Fundamental Concepts for New Clinical Trialists describes the core scientific concepts of designing, data monitoring, analyzing, and reporting clinical trials as well as the practical aspects of trials not typically discussed in statistical methodology textbooks. The first section of the book provides background information about clinical trials. It defines and compares clinical trials to other types of research studies and discusses clinical trial phases, registration, the protocol document, ethical issues, product development, and regulatory processes. It also includes a special chapter outlining the valuable attributes that statisticians can develop to maximize their contributions to a clinical trial. The second section examines scientific issues faced in each progressive step of a clinical trial. It covers issues in trial design, such as randomization, blinding, control-group selection, endpoint selection, superiority versus noninferiority, and parallel group versus crossover designs; data monitoring; analyses of efficacy, safety, and benefit-risk; and the reporting/publication of clinical trial results. As clinical trials remain the gold standard research studies for evaluating the effects of a medical intervention, newcomers to the field must have a fundamental understanding of the concepts to tackle real-world issues in all stages of trials. Drawing on their experiences in academia and industry, the authors provide a foundation for understanding the fundamental concepts necessary for working in clinical trials.

Originally published in 1997 Evolutionary Change addresses the somatic mechanism of change. Although astounding advances in molecular biology have opened up new engineering possibilities to shape our future in terms of "improving" the human species as well as eradicating all kinds of pathological characteristics of biological development, these possibilities pose potentially serious dangers. They arise primarily from the local nature of changes that are introduced and the impact of the environment on the overall development of the biological system. The book explores the biological mechanisms of change in their entirety - as they fit into the general dynamics of biological systems - and demonstrates the pitfalls of tackling change from a narrow perspective, using cancer as an example of certain pathological manifestations of these mechanisms of change.

This new book, Plant- and Marine- Based Phytochemicals for Human Health: Attributes, Potential, and Use, provides insight with scientific evidence on the use of medicinal plants in the treatment of certain diseases. It describes bioactive compounds of marine and plant origin that have been discovered to be advantageous for human health, shedding new light on the potential of phytochemicals on human health and contributing to the ocean of knowledge on phytochemistry and pharmaceutical biology. In addition, the role of plant-based pharmaceuticals is also discussed as an example of innovative uses of plant product. This book addresses the importance of phytochemicals from plants and marine life. It divided in four parts: Bioactive compounds in medicinal plants: status and potential Plant-based pharmaceuticals in human health: review Therapeutic attributes of mushroom, cereal grains, and legumes Innovative use of medicinal plants This compendium will be useful for the students and researchers as well as for industry professionals working in the food, nutraceuticals, and herbal industries.

This volume provides an integrated account of our current understanding of the functions of D-type cyclins during development and tumorigenesis, with special emphasis on the kinase-independent functions of these proteins. The volume will provide a thorough review of the latest discoveries on the new functions and interacting partners of mammalian cyclin Ds crucial to explain their oncogenic and differentiation properties in different cellular contexts. The volume begins with a historical perspective of how D-type cyclins were first discovered and eventually cloned from cancer tissues, followed by an account on the canonical functions of cyclin Ds during the G1-S transition of the cell cycle. Several chapters will be devoted to review the functions of D-type cyclins as transcriptional regulators and the mechanisms through which these novel functions could impact the tumorigenic process. Also discussed is emerging evidence that points to a role of D-type cyclins, particularly cyclin D1, as a cytoplasmic regulator of various cellular functions. This property, in human cells at least, is traceable to certain splice isoforms with novel oncogenic implications. Finally, a chapter is devoted to recent efforts to revise the canonical view of the "retinoblastoma pathway" to incorporate new evidence that suggests that cyclin D1's role in G1 is to singly-phosphorylate the retinoblastoma protein (pRb) for discrimination of target protein interactions. This work represents a significant departure from the view of cyclin D1 as a negative regulator of pRb and may have critical implications for understanding the function of antineoplastic agents that target the cyclin D1-associated kinases.

This critical review volume explores the theme of ABC transporters in the context of basic cancer research and its role in drug-resistant tumors. The chapters provided complement basic research by including investigations from translational applications to clinical oncology. The development of resistance is a major obstacle in cancer chemotherapy and the field has been moving rapidly in terms of determining the mechanisms for blocking ABC transporter-mediated drug efflux by specific inhibitors and thereby overcoming multidrug resistance. The volume covers these issues in careful detail. Additional topics include the relevance of ABC transporters in resistance to novel and established anticancer drugs and prognosis of patients to compounds, compounds used in photodynamic therapy, tyrosine kinase inhibitors and others. Furthermore, the potential of radiopharmaceuticals for diagnosis of multidrug-resistant tumors and of nanotechnology to combat drug-resistant tumors is also discussed.

This book gives a detailed yet clear insight into the current state of the art of the therapeutic application of bacteriophages in different conditions. The authors bring in their practical expertise within their respective fields of expertise and provide an excellent overview of the potential and actual use of phage therapy. Topics like economic feasibility compared to traditional antibiotics and also regulatory issues are discussed in far detail. This new volume is therefore a valuable resource for individuals engaged in the medical application of novel phage therapies.

This second edition provides a comprehensive laboratory manual on skeletal development and skeletal repair research utilizing mouse models. Chapters provide methods and protocols on the most current and cutting-edge techniques in skeletal development and repair, histological, cellular, and molecular techniques. 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, Skeletal Development and Repair: Methods and Protocols-Second Edition aims to ensure successful results in the further study of this vital field.

This book consists of four parts with 32 chapters adapted for four short courses, from the basic to the advanced levels of medical statistics (biostatistics), ideal for biomedical students . Part 1 is a compulsory course of Basic Statistics with descriptive statistics, parameter estimation and hypothesis test, simple correlation and regression. Part 2 is a selective course on Study Design and Implementation with sampling survey, interventional study, observational study, diagnosis study, data sorting and article writing. Part 3 is a specially curated course of Multivariate Analyses with complex analyses of variance, variety of regressions and classical multivariate analyses. Part 4 is a seminar course on Introduction to Advanced Statistical Methods with meta-analysis, time series, item response theory, structure equation model, multi-level model, bio-informatics, genetic statistics and data mining. The main body of each chapter is followed by five practical sections: Report Writing, Case Discrimination, Computer Experiments, Frequently Asked Questions and Summary, and Practice & Think. Moreover, there are 2 attached Appendices, Appendix A includes Introductions to SPSS, Excel and R respectively, and Appendix B includes all the programs, data and printouts for Computer Experiments in addition to the Tests for Review and the reference answers for Case Discrimination as well as Practice & Think.. This book can be used as a textbook for biomedical students at both under- and postgraduate levels. It can also serve as an importantguide for researchers, professionals and officers in the biomedical field.

There is an increasing need for educational resources for statisticians and investigators. Reflecting this, the goal of this book is to provide readers with a sound foundation in the statistical design, conduct, and analysis of clinical trials. Furthermore, it is intended as a guide for statisticians and investigators with minimal clinical trial experience who are interested in pursuing a career in this area. The advancement in genetic and molecular technologies have revolutionized drug development. In recent years, clinical trials have become increasingly sophisticated as they incorporate genomic studies, and efficient designs (such as basket and umbrella trials) have permeated the field. This book offers the requisite background and expert guidance for the innovative statistical design and analysis of clinical trials in oncology. Key Features: Cutting-edge topics with appropriate technical background Built around case studies which give the work a "hands-on" approach Real examples of flaws in previously reported clinical trials and how to avoid them Access to statistical code on the book's website Chapters written by internationally recognized statisticians from academia and pharmaceutical companies Carefully edited to ensure consistency in style, level, and approach Topics covered include innovating phase I and II designs, trials in immune-oncology and rare diseases, among many others

Platform trials test multiple therapies in one indication, one therapy for multiple indications, or both. These novel clinical trial designs can dramatically increase the cost-effectiveness of drug development, leading to life-altering medicines for people suffering from serious illnesses, possibly at lower cost. Currently, the cost of drug development is unsustainable. Furthermore, there are particular problems in rare diseases and small biomarker defined subsets in oncology, where the required sample sizes for traditional clinical trial designs may not be feasible. The editors recruited the key innovators in this domain. The 20 articles discuss trial designs from perspectives as diverse as quantum computing, patient's rights to information, and international health. The book begins with an overview of platform trials from multiple perspectives. It then describes impacts of platform trials on the pharmaceutical industry's key stakeholders: patients, regulators, and payers. Next it provides advanced statistical methods that address multiple aspects of platform trials, before concluding with a pharmaceutical executive's perspective on platform trials. Except for the statistical methods section, only a basic qualitative knowledge of clinical trials is needed to appreciate the important concepts and novel ideas presented.

The hallmark text for nursing faculty seeking to promote the transformative teaching of caring science, Creating a Caring Science Curriculum: A Relational Emancipatory Pedagogy for Nursing reflects the paramount scholarship of Caring Science educators. This second edition intertwines visionary thinking with blueprints, exemplars, and dynamic direction for the application of fundamental principles. It goes beyond the conventional by offering a model that serves as an emancipatory, ethical-philosophical, educational, and pedagogical learning guide for both teachers and students.Divided into five units, the text addresses the history of the caring curriculum revolution and its powerful presence within nursing. Unit I lays the foundation for a Caring Science curriculum. Unit II introduces intellectual and strategic blueprints for caring-based education, including action-oriented approaches for faculty-student relations, teaching/learning skills, pedagogical practices, critical-reflective-creative approaches to evolving human consciousness, and power relation dynamics. Unit III addresses curriculum structure and design, the evolution of a caring-based college of nursing, caring in advanced practice education, and the development of caring consciousness in nurse leaders. It also features real-world exemplars of Caring Science curricula. Unit IV includes an alternative approach to clinical and course-based evaluation, and the text concludes with an exploration of the future of the Caring Science curriculum as a way of emancipating the human spirit. Each chapter is structured to maximize engagement with reflective exercises and learning activities that encourage the integration of theory and practice into the learning process. New to This Edition: Updated chapters, case studies, and learning activities Six new chapters that provide guidance on how to create a Caring Science curriculum Exemplars from institutions that have developed Caring Science curricula Key Features: Provides a broad application of Caring Science for teachers, students, and nursing leaders Features case studies of teacher/student lived learning experiences within a caring-loving pedagogical environment Encourages the integration of theory and practice into the learning process with learning activities and reflective exercises Distills the expertise of world-renowned Caring Science scholars Purchase includes digital access for use on most mobile devices or computers

This book deals with the molecular mechanisms of membrane trafficking, a central eukaryotic cell biological process. In the post-genomic era many essential molecules involved in intracellular membrane/protein transport are emerging. A huge task now is to compile the molecular networks that govern these processes. Understanding of regulatory processes and participating molecules are likely to reveal global cellular regulatory circuits that couple membrane trafficking with other cellular functions. Such cell biological features are only starting to emerge. This book puts special emphasis on such mechanisms and processes. The contents discusses the role of coat proteins, tethering complexes, small rab GTPases, Sec1-family proteins and SNARE molecule phosphorylation in exocytosis, endocytosis and membrane fusion. In addition, the role of lipids in vesicle formation and membrane fusion, and some specialized cell biological denovo membrane generation processes are discussed.

The book endeavors to provide a stimulating and thought provoking scientific content to share and exchange new clinical studies and advancements in dealing with pulmonary diseases. The topics vary from clinical to translational research in respiratory diseases such as lung cancer, obstructive sleep apnea, chronic obstructive pulmonary disease, bacterial and fungal infections, lung lesions during febrile maladies, and others. An attempt has been made to show the intertwined relationship between the pulmonary system and other body systems such as kidney, cardiac, or hormonal functions. The ensuing interlocked morbidities, often exacerbating one another, require the coordination of various medical specialties to optimize the diagnostic and therapeutic processes. The knowledge sharing through publications of research and clinical experiences is indispensable to accelerate the innovation spectrum and to continue working on the therapeutic and preventive strategies in chronic pulmonary diseases. The book is addressed to pulmonologists, chest physicians, researchers, and healthcare professionals engaged in patient care.

This volume provides an updated collection of protocols for manipulating and studying VEGF signaling pathways in vitro and in vivo and aims to present a range of both firmly established and newly emerging technologies. Covering multiple model species, from mouse to zebrafish to human, the book explores the role of VEGF and VEGFR isoforms in exosomes, cultured cells, or in tissues, as well as robust cell assays for the investigation of basic angiogenic mechanisms and VEGF signaling in more complex cellular systems, amongst other subjects. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, VEGF Signaling: Methods and Protocols, Second Edition provides a useful tool for researchers in the vascular biology community and beyond in understanding the basic biology of VEGF signaling and in translating this research into the clinic.

With the critical role of statistics in the design, conduct, analysis and reporting of clinical trials or observational studies intended for regulatory purposes, numerous guidelines have been issued by regulatory authorities around the world focusing on statistical issues related to drug development. However, the available literature on this important topic is sporadic, and often not readily accessible to drug developers or regulatory personnel. This book provides a systematic exposition of the interplay between the two disciplines, including emerging themes pertaining to the acceleration of the development of pharmaceutical medicines to serve patients with unmet needs. Features: Regulatory and statistical interactions throughout the drug development continuum The critical role of the statistician in relation to the changing regulatory and healthcare landscapes Statistical issues that commonly arise in the course of drug development and regulatory interactions Trending topics in drug development, with emphasis on current regulatory thinking and the associated challenges and opportunities The book is designed to be accessible to readers with an intermediate knowledge of statistics, and can be a useful resource to statisticians, medical researchers, and regulatory personnel in drug development, as well as graduate students in the health sciences. The authors' decades of experience in the pharmaceutical industry and academia, and extensive regulatory experience, comes through in the many examples throughout the book.

The contributed volume "Multidisciplinarity and Interdisciplinarity in Health" is a health-centered volume of the Integrated Science Book series. Lack of confidence, lack of expertise, complexities of healthcare, the confusing nature of healthcare environments, and lack of organization and standardization can become obstacles to successful communication. This volume establishes how extensive is the interface between formal sciences and medical sciences on health-related issues. The book provides an overview of the value of the integration of formal, biological, and medical sciences and related products, i.e., health informatics and biomedical engineering, to frame a holistic approach to health systems, healthcare, medical practice, drug discovery, and medical device design. The book also focuses on innovative solutions to the most critical issues of different health crisis, including obesity, infectious outbreaks, and cancer that can be found by using an integrative approach. It also contains the fascinating crossroads between medical sciences, physics, and mind that is discussed from multiple perspectives on cognition, neuroscience, and psychiatry. These multidisciplinary considerations will expand the concepts of creativity, leadership, aesthetics, empathy and mental health.

Long non-coding RNAs (lncRNAs), tentatively defined as ncRNAs of more than two hundred nucleotides in length, are characterized by the complexity and diversity of their sequences and mechanisms of action. Based on genome-wide studies, more than 3,300 of them exist, but to date only the limited number of functional lncRNAs have been identified and characterized. Nonetheless, lncRNAs have emerged as key molecules involved in the control of transcriptional and posttranscriptional gene regulatory pathways. They take part in the recruitment of chromatin modifying complexes and regulate splicing, localization, stability and translation of the target mRNAs. This book provides an overview of the rapidly advancing field of long ncRNAs, describing the epigenetic and non-epigenetic mechanisms by which they regulate various biological functions in model systems, from yeast to mammals. The role of ncRNAs in sex chromosome dosage compensation in flies and mammals is described, as well as their role in centromere and telomere biology. Long non-coding RNAs involved in environmental stress response and development are presented and their mechanisms of action discussed.

Methods of proteomics have been shown to be powerful tools in search of target proteins - proteins that respond in cells to an internal or an external stimulus. Proteomics is widely used in biomedical research. However, in radiation biology research, following exposures of living matter to low doses of either ionizing or non-ionizing radiation, proteomics approach is only very slowly gaining support. This book, by presenting the current status of the use of proteomics in radiation biology, will help to attract attention to the field of radiation proteomics.