Recent Advancement in Prodrugs Drugs used as medicines have many limitations like low chemical stability, aqueous solubility, or oral absorption/bioavailability, rapid presystemic metabolism, toxicity, inadequate site specificity, or poor patient acceptance/compliance (unwanted adverse effects, unacceptable taste or odor, irritation or pain). Prodrugs design is an approach to overcome these limitations. Key features Covers recent advancements in development of prodrugs Presents balanced synthesis and applications of prodrug chemistry Discusses broad spectrum of prodrug categories and outlines industrial applications Reviews prodrugs in cancer nanomedicine, its therapy and treatment Elucidates mathematical models to study the kinetics of prodrugs This book covers recent advances in the design of prodrugs. It contains all the significant recent examples of prodrug chemistry developments and will aid academics and researchers seeking to generate new projects in the field.

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.

Building on its best-selling predecessors, Basic Statistics and Pharmaceutical Statistical Applications, Third Edition covers statistical topics most relevant to those in the pharmaceutical industry and pharmacy practice. It focuses on the fundamentals required to understand descriptive and inferential statistics for problem solving. Incorporating new material in virtually every chapter, this third edition now provides information on software applications to assist with evaluating data. New to the Third Edition Use of Excel (R) and Minitab (R) for performing statistical analysis Discussions of nonprobability sampling procedures, determining if data is normally distributed, evaluation of covariances, and testing for precision equivalence Expanded sections on regression analysis, chi square tests, tests for trends with ordinal data, and tests related to survival statistics Additional nonparametric procedures, including the one-sided sign test, Wilcoxon signed-ranks test, and Mood's median test With the help of flow charts and tables, the author dispels some of the anxiety associated with using basic statistical tests in the pharmacy profession and helps readers correctly interpret their results using statistical software. Through the text's worked-out examples, readers better understand how the mathematics works, the logic behind many of the equations, and the tests' outcomes.

New Developments in Dementia Prevention Research addresses a dearth of knowledge about dementia prevention and shows the importance of considering the broader social impact of certain risk factors, including the role we each play in our own cognitive health throughout the lifespan. The book draws on primary and secondary research in order to investigate the relationship between modifiable factors, including vascular and psychosocial risks, that may affect the incidence of dementia. Bringing together world-leading expertise from applied science, medicine, psychology, health promotion, epidemiology, health economics, social policy and primary care, the book compares and contrasts scientific and service developments across a range of settings. Each chapter presents these themes in a way that will ensure best practice and further research in the field of dementia prevention is disseminated successfully throughout the world. Perhaps most importantly, chapters also question what type of social responsibility we are prepared to embrace in order to address the challenges inherent in dementia prevalence. New Developments in Dementia Prevention Research includes contributions from leading authorities in brain health and dementia prevention and provides an essential contribution to the discourse on dementia prevention. It will be of great interest to academics, researchers and postgraduate students engaged in the study of the psychological and social aspects of aging and dementia.

The aim of this book is to equip biostatisticians and other quantitative scientists with the necessary skills, knowledge, and habits to collaborate effectively with clinicians in the healthcare field. The book provides valuable insight on where to look for information and material on sample size and statistical techniques commonly used in clinical research, and on how best to communicate with clinicians. It also covers the best practices to adopt in terms of project, time, and data management; relationship with collaborators; etc.

In clinical trial practice, controversial statistical issues inevitably occur regardless of the compliance with good statistical practice and good clinical practice. But by identifying the causes of the issues and correcting them, the study objectives of clinical trials can be better achieved. Controversial Statistical Issues in Clinical Trials covers commonly encountered controversial statistical issues in clinical trials and, whenever possible, makes recommendations to resolve these problems. The book focuses on issues occurring at various stages of clinical research and development, including early-phase clinical development (such as bioavailability/bioequivalence), bench-to-bedside translational research, and late-phase clinical development. Numerous examples illustrate the impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation. The author also offers recommendations regarding possible resolutions of the problems. Written by one of the preeminent experts in the field, this book provides a useful desk reference and state-of-the art examination of problematic issues in clinical trials for scientists in the pharmaceutical industry, medical/statistical reviewers in government regulatory agencies, and researchers and students in academia.

Researching, Reflecting and Writing about Work provides a guide to the research skills and critical thinking required to complete a research project for professional learning courses in counselling and psychotherapy.

Written at a level easily accessible to those enrolled on a work-based qualification as well as those considering postgraduate research at master's level, this book includes:

• how we reflect on our work
• discussion on preparation and structuring of a case study
• how to present work in supervision with advice on process recording
• essay plan structures and appropriate methodologies for research
• ethical considerations and critical linking
• dilemmas and tensions involved in 'research at work'.

Key learning points and reflective exercises are included throughout and theory is supported by contributions detailing specific learning experiences from a variety of work settings, including the public sector, an organisation, in the community, and as an independent counsellor in a voluntary agency. There is also a section on how to prepare your research for consideration for publication and how to present your findings to colleagues.

Researching, Reflecting and Writing about Work will be of interest to all those on counselling courses, or training as psychotherapists, as well as people involved in professional learning linked to the helping professions, including those interested in work-based research linked to therapy in any setting.

This book is an updated reference for one of the most exciting field of biomedical researches- Stem Cell Research and its therapeutic applications. Stem cell research holds great promise for the treatment of many human diseases that currently lack effective therapies. The set of chapters in this book provide insights into both basic stem cell biology and clinical applications of stem cell-based cell replacement therapies for a variety of human diseases, including cardiovascular diseases, neurological disorders, and li ver degeneration. It also covers novel technologies for the culture and differentiation of both human embryonic stem cells and adult tissue stem cells. This book summarizes our current state of knowledge in stem cell research and integrates basic stem cell biology with regenerative medicine in an overall context. It is an essential reference for students, postdoctoral fellows, academic and industrial scientists, and clinicians. v Acknowledgements The editors would like to thank Ms. Jill Brantley, Rose Chavarin, Alina Haas, and Emily Sun for their administrative assistance and proof-reading of this book. We would also like to thank all the authors for their contributions. vii The editors wish to dedicate this book to our mentors Ron Evans, Fred Gage, and, in memory of Daniel E. Koshland, Jr. Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi 1 Retinal Pigment Epithelial Cells: Development In Vivo and Derivation from Human Embryonic Stem Cells In Vitro for Treatment of Age-Related Macular Degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Dennis O. Clegg, David Buchholz, Sherry Hikita, Teisha Rowland, Qirui Hu, and Lincoln V.

Measures of Interobserver Agreement and Reliability, Second Edition covers important issues related to the design and analysis of reliability and agreement studies. It examines factors affecting the degree of measurement errors in reliability generalization studies and characteristics influencing the process of diagnosing each subject in a reliability study. The book also illustrates the importance of blinding and random selection of subjects. New to the Second Edition New chapter that describes various models for methods comparison studies New chapter on the analysis of reproducibility using the within-subjects coefficient of variation Emphasis on the definition of the subjects' and raters' population as well as sample size determination This edition continues to offer guidance on how to run sound reliability and agreement studies in clinical settings and other types of investigations. The author explores two ways of producing one pooled estimate of agreement from several centers: a fixed-effect approach and a random sample of centers using a simple meta-analytic approach. The text includes end-of-chapter exercises as well as downloadable resources of data sets and SAS code.

In response to the US FDA's Critical Path Initiative, innovative adaptive designs are being used more and more in clinical trials due to their flexibility and efficiency, especially during early phase development. Handbook of Adaptive Designs in Pharmaceutical and Clinical Development provides a comprehensive and unified presentation of the principles and latest statistical methodologies used when modifying trial procedures based on accrued data of ongoing clinical trials. The book also gives a well-balanced summary of current regulatory perspectives. The first several chapters focus on the fundamental theory behind adaptive trial design, the application of the Bayesian approach to adaptive designs, and the impact of potential population shift due to protocol amendments. The book then presents a variety of statistical methods for group sequential design, classical design, dose-finding trials, Phase I/II and Phase II/III seamless adaptive designs, multiple stage seamless adaptive trial design, adaptive randomization trials, hypotheses-adaptive design, and treatment-adaptive design. It also covers predictive biomarker diagnostics for new drug development, clinical strategies for endpoint selection in translational research, the role of independent data monitoring committees in adaptive clinical trials, the enrichment process in targeted clinical trials for personalized medicine, applications of adaptive designs that use genomic or genetic information, adaptive trial simulation, and the efficiency of adaptive design. The final chapters discuss case studies as well as standard operating procedures for good adaptive practices. With contributions from leading clinical researchers in the pharmaceutical industry, academia, and regulatory agencies, this handbook offers an up-to-date, complete treatment of the principles and methods of adaptive design and analysis. Along with reviewing recent developments, it examines issues commonly encountered when applying adaptive design methods in clinical trials.

Focusing on group sequential procedures, summarizes the sequential statistical methods used in anticancer, antiviral, cardiovascular, and gastrointestinal drug research and screening. The clinical and preclinical applications are mainly presented as case studies, many of which form part of New Drug

The objective of this CTMI volume is to provide readers with a foundation for understanding what ADARs are and how they act to affect gene expression and function. Because A-to-I editing may affect base-pairing and RNA structure, processes including translation, splicing, RNA replication, and miR and siRNA silencing may be affected. It also is becoming increasingly apparent that ADARs may possess roles not only as enzymes that deaminate adenosine to produce inosine in RNA substrates with double-stranded character, but also as proteins independent of their catalytic property. Future studies of ADARs no doubt will provide us with additional surprises and new insights into the modulation of biological processes by the ADAR family of proteins.

The EuroQol Group first met in Rotterdam in May 1987 determined to develop a standardised non-disease-specific instrument for valuing health-related quality of life. The book traces the activities of the Group over the next 25 years. The instrument constructed, eventually named the EQ-5D, was translated into many languages and used in a wide range of countries and settings. The book describes how the instrument's descriptive system was determined, how translation and language issues were handled, and how valuations were provided. Recent developments, in particular a 5-level version (EQ-5D-5L), and a youth version (EQ-5D-Y) are covered. The history of the institutional and administrative framework within which the Group operated is also treated.

A Practical Guide to Managing Clinical Trials is a basic, comprehensive guide to conducting clinical trials. Designed for individuals working in research site operations, this user-friendly reference guides the reader through each step of the clinical trial process from site selection, to site set-up, subject recruitment, study visits, and to study close-out. Topics include staff roles/responsibilities/training, budget and contract review and management, subject study visits, data and document management, event reporting, research ethics, audits and inspections, consent processes, IRB, FDA regulations, and good clinical practices. Each chapter concludes with a review of key points and knowledge application. Unique to this book is "A View from India," a chapter-by-chapter comparison of clinical trial practices in India versus the U.S. Throughout the book and in Chapter 10, readers will glimpse some of the challenges and opportunities in the emerging and growing market of Indian clinical trials.

The concepts of estimands, analyses (estimators), and sensitivity are interrelated. Therefore, great need exists for an integrated approach to these topics. This book acts as a practical guide to developing and implementing statistical analysis plans by explaining fundamental concepts using accessible language, providing technical details, real-world examples, and SAS and R code to implement analyses. The updated ICH guideline raises new analytic and cross-functional challenges for statisticians. Gaps between different communities have come to surface, such as between causal inference and clinical trialists, as well as among clinicians, statisticians, and regulators when it comes to communicating decision-making objectives, assumptions, and interpretations of evidence. This book lays out a path toward bridging some of these gaps. It offers A common language and unifying framework along with the technical details and practical guidance to help statisticians meet the challenges A thorough treatment of intercurrent events (ICEs), i.e., postrandomization events that confound interpretation of outcomes and five strategies for ICEs in ICH E9 (R1) Details on how estimands, integrated into a principled study development process, lay a foundation for coherent specification of trial design, conduct, and analysis needed to overcome the issues caused by ICEs: A perspective on the role of the intention-to-treat principle Examples and case studies from various areas Example code in SAS and R A connection with causal inference Implications and methods for analysis of longitudinal trials with missing data Together, the authors have offered the readers their ample expertise in clinical trial design and analysis, from an industrial and academic perspective.

Bioactive lipid metabolism and signaling are now widely accepted as major players in cancer biology. This volume helps to fill the urgent need to explore and investigate the innovations, current shortcomings, and future challenges of cancer therapy through the bioactive lipids by presenting new research on the use of bioactive lipids as effective weapons against cancer. The volume introduces the subject and then goes on to cover the chemistry, formulation, and mechanism of bioactive lipids in cancer. The volume takes a close look at lipoxins, ceramides, resolvins, and sphingosine-1-phosphate and their roles in cancer treatment. It also addresses the formulations based on bioactive lipids for the treatment of cancer. A variety of mechanisms of bioactive lipids as novel therapies are also covered, including using computational techniques to identify bioactive lipid drug targets, targeting therapy via KRAS and PI3K signals, and others. The authors also discuss the role and effects of various substances and their effect on various cancers, including colorectal cancer, prostate cancer, breast cancer, and others. The application of lysophosphatidic acid, lipopolysaccharide, lipid-soluble bioactive substance from avocado, omega-3 polyunsaturated fatty acids-derived lipid metabolites, and more are covered as well. The volume offers academia, technologists, and scientists from different disciplines valuable information to gain knowledge of bioactive lipid metabolism and signaling as an anti-cancer weapon in their fight against cancer.

Thin layer chromatography (TLC) is well suited for performing enantioseparations for research as well as larger-scale applications. A fast, inexpensive, and versatile separation technique, there are many practical considerations that contribute to its effectiveness. Thin Layer Chromatography in Chiral Separations and Analysis is the first book to focus solely on the theory, capabilities, and applications of TLC for direct and indirect enantioseparations. The first part of the book examines the fundamental principles of chirality and TLC. It describes the necessary materials, laboratory equipment, procedures, and strategies for the separation, quantification, isolation, and analysis of chiral compounds. The second part evaluates the real-world enantioseparations and densitometric analyses. Emphasizing pharmaceutical applications, the book discusses chiral separation mechanisms and methods for analyzing the chiral purity of diastereoisomers, amino acids, beta-blockers, and NSAIDS. Topics also include commercial stationary phases and chiral modifiers of mobile phases. Thin Layer Chromatography in Chiral Separations and Analysis presents a unified perspective of theory and experimental details underlying the collective developments in the field. The book offers scientists in a variety of disciplines and levels of expertise a complete guide to understanding the current and potential applications of chiral TLC.

It is pointed out that a cancer stem cell is a type within a tumor that possesses the capacity of self-renewal and can give rise to the heterogeneous lineages of cancer cells, which comprise the tumor. It is emphasized that a unique feature of cancer stem cells is that, although conventional chemotherapy kills most cells in a tumor, cancer stem cells remain intact. Vast applications of the following specific stem cells in disease and tissue injury are discussed: embryonic stem cells, human mesenchymal stem cells, cancer stem cells, arterial stem cells, neural stem cells, cardiac stem cells, dental stem cells, limbal stem cells, and hematopoietic stem cells. Because human embryonic stem cells possess the potential to produce unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential in this volume. These cells are used in tissue engineering, regenerative medicine, pharmacological and toxicological studies, and fundamental studies of cell differentiation. It is pointed out that the formation of embryoid bodies, which are three-dimensional aggregates of embryonic cells, is the initial step in the differentiation of these cells. Therapeutic implications of signalling pathways in cancer stem cells are pointed out. Targeting self-renewal pathways in cancer stem cells are also included. Application of mesenchymal stem cells for treating ischemic brain injury is explained. Neural stem cells proliferation into the surrounding area of the traumatic brain injury is explained.

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Since the last major compendium dedicated to cyclic nucleotide phosphodiesterases (PDEs) was published over 15 years ago, an enormous amount of progress has occurred in the field. There is great need for a centralized source for key information in this burgeoning and therapeutically important area of medical research. Cyclic Nucleotide Phosphodiesterases in Health and Disease provides an integrated volume covering PDE biology from genes to organisms. It examines phosphodiesterases as pharmacological targets as well as the development of specific PDE inhibitors as therapeutic agents. With contributions from pioneers in the field, individual chapters describe one of the 11 known mammalian PDE families including the molecular characteristics, structure, function, and traits unique to each. Characteristics of PDEs from lower organisms are also the subject of other chapters since they provide key insights into PDE functions and are also pharmacological targets for treatment of a variety of diseases in humans and domestic animals. Chapters on the current biomedical and therapeutic research on PDEs include studies on gene-targeted knockout strategies and compartmentation in cyclic nucleotide signaling. By unraveling the unique cellular roles for different PDEs, scientists are beginning to open the door to the therapeutic use of PDE inhibitors for the treatment of a number of pathological conditions including asthma and inflammation, pulmonary hypertension, erectile dysfunction, and stroke. By collating current information into a coherent and coordinated perspective, Cyclic Nucleotide Phosphodiesterases in Health and Disease provides an invaluable reference for industry and clinical scientists and points toward future directions of research and therapeutic advancements in developing selective inhibitors for these various enzymes.

This open access book is the first published guide about how to analyse data produced by the EQ-5D, one of the most widely used Patient Reported Outcomes questionnaires world wide. The authors provide practical, clear and comprehensive guidance in five concise chapters. Following an overview of the EQ-5D and its analysis, we describe how the questionnaire data - the EQ-5D profile and EQ VAS - can be analysed in different ways to generate important insights into peoples' health. We then show how the value sets which accompany the EQ-5D can be applied to summarise patients' data. The final chapter deals with advanced topics, including the use of Minimally Important Differences, case-mix adjustment, mapping, and more. This book is essential for those new to analyzing EQ-5D data and will be also be valuable for those with more experience. The methods can be applied to any EQ-5D instrument (for example, the three- and five-level and Youth versions) and many of the methods described will be equally relevant to other Patient Reported Outcomes instruments.

Humans have engaged in theatre for at least 50,000 years for good reason: it builds social connections, provides opportunities to learn, and creates meaning through storytelling. Perhaps most importantly, it is an enjoyable, and therefore self-reinforcing, activity. Theatre offers readers an introduction to the role that theatre plays in health and wellbeing, and provides guidance on how to incorporate it into professional health and social care environments, community spaces, and the family home. The book provides an overview of the current evidence demonstrating the effects of theatre on specific domains of health and wellbeing, including mental health, physical health, and public health, as well as its impacts on the education of health and social care professionals. Case studies illustrate the broad range of applied theatre methods currently in use across the human lifespan - from bedside theatre performed for children in hospital to theatre workshops for people living with dementia and theatre-based interpersonal communication training for medical students. Theatre also delivers plenty of practical advice on how to bring theatre into health and social care environments, including step-by-step instructions for specific activities, insights into potential barriers, and (most importantly) strategies needed to overcome them with empathy, collaboration, and creativity. This volume will be useful to professionals working in health and social care settings, as well as to theatre artists and educators who already are or who would like to work in health or social care settings with special populations.

A comprehensive guide for physicians conducting clinical research, this second edition addresses a broader research perspective. It includes information on the implications of the ICH Guidelines, current FDA regulations, and an Internet address directory. Everything the clinical trial manager, planner, monitor, and investigator need to know about the design, establishment, monitoring, and close-out of a trial is in this book. The chapters address the elements of clinical research, professional interactions, FDA regulations and good clinical practices guidelines, investigational agent management, designing a study and protocol development, conducting the study, and more.

This volume describes important medical discoveries, from the introduction of the first antibiotic to the present, where serendipity, intuition, coincidence, or laboratory accident played an important role in bringing a discovery to light. Although chance is the principal determinant, the book emphasizes other factors, such as economic and political exigencies and being in the right place at the right time.

It is estimated that 80 to 90% of drugs under development never make it to the marketplace due to insufficient clinical activity, unacceptable toxicity, rapid appearance of drug resistance, or other factors that should be, at least partially, predictable from preclinical testing. This new text asks the question, "How can we use computational methods to improve the success rate in drug development?" Computer Techniques in Preclinical and Clinical Drug Development shows how modeling makes it possible to extract the maximum amount of information and predictive value from preclinical data. Computer modeling methods from the areas of pharmacokinetics, pharmacodynamics, cytokinetics, and inhibition kinetics of multi-enzyme pathways are all discussed in this unique reference source.

Gives a convenient summary of trials in Gynecologic Oncology Supplies an invaluable revision primer for those undertaking certification Provides a uniquely up-to-date resource