In 1993, the genetic mutation responsible for Huntington's disease (HD) was identified. Considered a milestone in human genomics, this discovery has led to nearly two decades of remarkable progress that has greatly increased our knowledge of HD, and documented an unexpectedly large and diverse range of biochemical and genetic perturbations that seem to result directly from the expression of the mutant huntingtin gene. Neurobiology of Huntington's Disease: Applications to Drug Discovery presents a thorough review of the issues surrounding drug discovery and development for the treatment of this paradigmatic neurodegenerative disease. Drawing on the expertise of key researchers in the field, the book discusses the basic neurobiology of Huntington's disease and how its monogenic nature confers enormous practical advantages for translational research, including the creation of robust experimental tools, models, and assays to facilitate discovery and validation of molecular targets and drug candidates for HD. Written to support future basic research as well as drug development efforts, this volume: Covers the latest research approaches in genetics, genomics, and proteomics, including high-throughput and high-content screening Highlights advances in the discovery and development of new drug therapies for neurodegenerative disorders Examines the practical realities of preclinical testing, clinical testing strategies, and, ultimately, clinical usage While the development of effective drug treatments for Huntington's disease continues to be tremendously challenging, a highly interactive and cooperative community of researchers and clinical investigators now brings us to the threshold of potential breakthroughs in the quest for therapeutic agents. The impressive array of drug discovery resources outlined in the text holds much promise for treating this devastating disease, providing hope to long-suffering Huntington's disease patients and their families.

Features Represents the first book to provide comprehensive coverage of model-assisted designs for various types of dose-finding and optimization clinical trials Describes the up-to-date theory and practice for model-assisted designs Presents many practical challenges and issues arising from early-phase clinical trials Illustrates with many real trial applications Offers numerous tips and guidance on designing dose finding and optimization trials Provides step-by-step illustration of using software to design trials Develops a companion website (www.trialdesign.org) to provide easy-to-use software to assist learning and implementing model-assisted designs.

This detailed volume explores the methods used for most of the recent approaches to suicide gene therapy of cancer, which exploits promoters that are specific to cancer cells, thereby ensuring (or greatly increasing the likelihood) that the therapeutic gene is expressed only in cancer cells. The book also contains chapters describing methods to improve the safety of cell therapy and techniques utilizing bone marrow mesenchymal cells. 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 practical, Suicide Gene Therapy: Methods and Protocols serves as an ideal guide for researchers expanding upon our knowledge and application of this vital form of cancer therapy.

The aim of this unique volume is to help medical researchers design clinical trials to improve survival, remission duration, or time to recurrence of disease. Written in a user-friendly step-by-step format, this work enables the researcher-with no background in statistics-to determine sample size and write statistical considerations for their protocols. It provides critical language which can help with FDA submissions and/or research grants. It also provides the mathematical justification of the material at a level consistent with one year of undergraduate mathematical statistics. It presents survival analysis methods at a more elementary level than any known text. Filled with tables, figures, plus an extensive appendix, this one-of-a-kind reference is an absolute must for all clinical researchers and biostatisticians.

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

Participatory Visual Methodologies in Global Public Health focuses on the use of participatory visual methodologies such as photovoice, participatory video (including cellphilming or the use of cell phones to make videos), drawing and mapping in public health research. These approaches are modes of inquiry that can engage participants and communities, eliciting evidence about their own health and well-being, as well as modes of representation and modes of production in the co-creation of knowledge, and modes of dissemination in relation to knowledge translation and mobilization. Thus, the production by a group of girls or young women of a set of photos or videos from their own visual perspective can offer new evidence on how, for example, they see sexual violence. Unlike other data such as those collected through surveys or even conventional interviews, the images they have produced not only inform the empirical evidence, but also do not need to remain in a laboratory or the office of a researcher. They can, through exhibitions and screenings, reach various audiences: school or health personnel, parents and community members, and perhaps also policy-makers. This collection offers a critical overview for students, practitioners, researchers and policy-makers working in or concerned with the use of participatory methodologies in public health around the globe. This book was originally published as a special issue of Global Public Health.

This is the first book that comprehensively and systematically describes the new technology of hydrophilic interaction liquid chromatography (HILIC). Hydrophilic interaction chromatography is a separation technique suitable for polar and hydrophilic compounds and orthogonal to reversed phase liquid chromatography. From small organic molecules to proteins, the text explores the many applications of HILIC in the analytical field. Winner of the President's Award for Excellence, the author explains how HILIC can significantly improve analytical throughput by shortening sample preparation procedure, which is one of the bottlenecks for drug discovery and development in the pharmaceutical industry.

Written by the international community's leading experts, Trace Elements in Laboratory Rodents describes the best and most current methods to provide deficient or supplemental trace elements to laboratory animals, as well as how to assay them. The experts warn of the common pitfalls and hidden problems in nutritional testing and how to avoid them. This how-to approach focuses on the technical details that make good, reliable studies. Common as well as rare or recently recognized minerals are described relating to both dietary supplementation and measurement in tissues.
If you are a researcher, professor, or student working in nutrition, food science, biochemistry, or veterinary medicine, you can't afford to be without this excellent hands-on methods manual!

Animal Models for the Study of Human Disease, Second Edition, provides needed information on model sharing, animal alternatives, animal ethics and access to databanks of models, bringing together common descriptions of models for busy researchers across biomedical and biological sciences. Offering easily searchable advantages and disadvantages for each animal model and organized by disease topics, this resource aids researchers in finding the best animal model for research in human disease.

This volume of the Biostatistics and Health Sciences Set focuses on statistics applied to clinical research. The use of SAS for data management and statistical modeling is illustrated using various examples. Many aspects of data processing and statistical analysis of cross-sectional and experimental medical data are covered, including regression models commonly found in medical statistics. This practical book is primarily intended for health researchers with a basic knowledge of statistical methodology. Assuming basic concepts, the authors focus on the practice of biostatistical methods essential to clinical research, epidemiology and analysis of biomedical data (including comparison of two groups, analysis of categorical data, ANOVA, linear and logistic regression, and survival analysis). The use of examples from clinical trials and epidemiological studies provide the basis for a series of practical exercises, which provide instruction and familiarize the reader with essential SAS commands.

What constitutes qualitative evidence? This book breaks new ground by providing urgently needed standards for qualitative inquiry and addresses the significant issues of what constitutes qualitative evidence. In particular, this book will address the place of qualitative evidence in the planning delivery, and evaluation of health care. The authors first examine the status of qualitative research as evidence versus "opinion." They then examine such topics as: who decides what counts as evidence, the nature of outcomes, how to evaluate qualitative evidence, constructing evidence within the qualitative project, and research utilization and qualitative research. They conclude with perspectives on the issue of standards for qualitative investigation.

Clinical Trial Optimization Using R explores a unified and broadly applicable framework for optimizing decision making and strategy selection in clinical development, through a series of examples and case studies. It provides the clinical researcher with a powerful evaluation paradigm, as well as supportive R tools, to evaluate and select among simultaneous competing designs or analysis options. It is applicable broadly to statisticians and other quantitative clinical trialists, who have an interest in optimizing clinical trials, clinical trial programs, or associated analytics and decision making. This book presents in depth the Clinical Scenario Evaluation (CSE) framework, and discusses optimization strategies, including the quantitative assessment of tradeoffs. A variety of common development challenges are evaluated as case studies, and used to show how this framework both simplifies and optimizes strategy selection. Specific settings include optimizing adaptive designs, multiplicity and subgroup analysis strategies, and overall development decision-making criteria around Go/No-Go. After this book, the reader will be equipped to extend the CSE framework to their particular development challenges as well.

This detailed book provides an accessible compendium of up-to-date methods in the fields of environmental toxicology, molecular toxicology, and toxicogenomics. Organized into four major sections, the volume examines methods utilizing model animal species, such as nematode, fruit fly, mice, chicken, and amphibians, methods using plants to study chemical toxicity, applying the Ames assay to chemical mutagenicity study, as well as methods for environmental chemical analysis. Although this book is divided into these parts, the methods can be used across species. 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 practical, Environmental Toxicology and Toxicogenomics: Principles, Methods, and Applications serves as a valuable resource for the scientific community, particularly for young scientists and graduate and undergraduate students, inspiring more research in the vitally important field of environmental toxicity, molecular toxicology, and toxicogenomics.

How do we identify and measure human disease in the past? In the absence of soft tissue, paleoepidemiologists have developed ingenious ways of assessing illness and mortality in archaeological populations. In this volume, the key methods of epidemiology are outlined for non-specialists, showing the importance of studying prevalence over incidence, adjustments needed in studying past groups, how to compare studies, and the dangers of assessing occupation based upon bone evidence. A model for planning a proper paleoepidemiological study concludes the volume. Both as an introduction to epidemiology for archaeologists, and as a primer on archaeological analysis for epidemiologists, this book should serve the needs of both populations.

This volume explores the recent advances in the study of translational paths in central inflammation and focuses on ongoing pathophysiological processes and the transition between inflammatory stages and progressive states with neurodegeneration. Chapters cover topics such as pathophysiological hallmarks of neuroinflammation from tissue damage to reorganization; connecting studies of mouse models; and investigations of humans with multiple sclerosis. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and practical, Translational Methods for Multiple Sclerosis Research is a valuable resource for researchers who want to learn more about this chronic ad progressive disease, and pave the way for new advancements.

Translating laboratory discoveries into successful therapeutics can be difficult. Clinical Trials in Neurology aims to improve the efficiency of clinical trials and the development of interventions in order to enhance the development of new treatments for neurologic diseases. It introduces the reader to the key concepts underpinning trials in the neurosciences. This volume tackles the challenges of developing therapies for neurologic disorders from measurement of agents in the nervous system to the progression of clinical signs and symptoms through illustrating specific study designs and their applications to different therapeutic areas. Clinical Trials in Neurology covers key issues in Phase I, II and III clinical trials, as well as post-marketing safety surveillance. Topics addressed include regulatory and implementation issues, outcome measures and common problems in drug development. Written by a multidisciplinary team, this comprehensive guide is essential reading for neurologists, psychiatrists, neurosurgeons, neuroscientists, statisticians and clinical researchers in the pharmaceutical industry.

When a patient is diagnosed with a gynecological malignancy, she and her doctors must make urgent, high-risk decisions about her course of treatment. In selecting an appropriate plan of care, physicians must weigh the patient's individual needs, the tumor's specific characteristics, and the treatment's potential side effects. Because there is no one-size-fits-all treatment solution, a plethora of clinical trials have been performed on ovarian cancer patients, but clinicians may struggle to keep up with this ever-growing body of research. Collecting and synthesizing research findings from a wide array of medical journal articles and book chapters, Clinical Trials in Ovarian Cancer provides physicians with an invaluable resource. Gynecologic oncologist Christine S. Walsh systematically outlines each of the seminal Phase III trials that have shaped the treatment of ovarian cancers, detailing the rationale for the trial, the patient population studied, treatment delivery methods, efficacy, toxicity, and trial conclusions. She provides a clear overview of established treatments, as well as still-controversial experimental approaches. The first book to organize this cutting-edge research into an easy-to-use reference, Clinical Trials in Ovarian Cancer should help medical personnel at all levels provide their patients with the highest standard of care.

Mammalian cell lines command an effective monopoly for the production of therapeutic proteins that require post-translational modifications. This unique advantage outweighs the costs associated with mammalian cell culture, which are far grater in terms of development time and manufacturing when compared to microbial culture. The development of cell lines has undergone several advances over the years, essentially to meet the requirement to cut the time and costs associated with using such a complex hosts as production platforms.

This book provides a comprehensive guide to the methodology involved in the development of cell lines and the cell engineering approach that can be employed to enhance productivity, improve cell function, glycosylation and secretion and control apoptosis. It presents an overall picture of the current topics central to expression engineering including such topics as epigenetics and the use of technologies to overcome positional dependent inactivation, the use of promoter and enhancer sequences for expression of various transgenes, site directed engineering of defined chromosomal sites, and examination of the role of eukaryotic nucleus as the controller of expression of genes that are introduced for production of a desired product. It includes a review of selection methods for high producers and an application developed by a major biopharmaceutical industry to expedite the cell line development process. The potential of cell engineering approch to enhance cell lines through the manipulation of single genes that play important roles in key metabolic and regulatory pathways is also explored throughout.

The set of techniques known collectively as real-time data capture (RTDC) is becoming increasingly important in medical research. Based on the collection of data in people's typical environments, RTDC is primarily used with self-reported data, such as medical symptoms and psychological states. Now, its guiding principles and supporting technologies also provide a framework for scientists to monitor physiological information such as heart rate, blood pressure, and skin conductance. This volume gives the most complete view yet of the state of RTDC science and its potential for use across the health and behavioural sciences.

This book is designed to collect and review the research covering main directions in investigations of aromatic nitroso compounds in last decades, and to present both, the academic aspects of this chemistry, as well as the open field of its applicability. The book is divided in five chapters. The basic structural properties of the nitroso aromatic molecules are described in the first chapter. The second chapter is an overview of the methods of preparations of aromatic nitroso and polynitroso compounds, including classical synthetic methods and some new preparative approaches. The third part deals with the physico-chemical properties of nitroso aromates and azodioxides, its structure, crystallography, quantum chemical calculations, spectroscopy, typical reactions, and especially it is focused on the dimerizations in the solid-state. In the fourth chapter is represented organometallic chemistry of nitroso aromatic molecules and its applications in catalysis. The last part of the book deals with the behavior of this class of compounds in the biological systems, reactions with biomolecules and the use in toxicology.

This issue of Medical Clinics, guest edited by Dr. Thomas G. DeLoughery, is devoted to anemia. Articles in this issue include: Anemia: Evaluation and Diagnostic Tests; Anemia of Chronic Disease; B12/Folate Deficiency; Iron Deficiency; Myelodysplasia; Autoimmune Hemolytic Anemia; Congenital Hemolytic Anemia; Sickle Cell Disease; Thrombotic Microangiopathy; Unusual Anemias; and Transfusion Therapy.

This volumes details methods focusing on technological innovation and recent advances in diabetes management. Chapters will guide readers through recent advances, beta-cell regeneration, non-invasive imaging of endogenous, transplanted islets theranostics, microRNA profiling of beta-cells and artificial intelligence, and deep learning algorithms in diabetes. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Type-1 Diabetes: Methods and Protocols is for a broad audience including basic researches, clinicians, and physician scientists whose major focus is in diabetes.

This issue of the Psychiatric Clinics of North America will review Clinical issues and Affirmative Treatments with Transgendered Clients. Edited by Lynne Carroll and lore m. dickey, subjects discussed in the text include, but are not limited to, Assessing Transgender and Gender Nonconforming Clients; Recommending Clients for Gender Transition; Psychodynamic Approaches in Clinical Practice with Gender Nonconforming and Gender Diverse Youth; Family Treatment with Transgender or Gender Nonconforming Children and Adolescents; Cognitive Behavioral Therapy with Transgender Adults; Therapeutic Issues with Transgender Elders; Hormonal and Surgical Treatment options; Transgender and Gender Diverse Clients with Co-Occurring Mental Disorders; DSM-V Coding; and Past and Future Challenges, among others.

This book centers on gene therapy and gene transfer approaches to prevent or treat chronic virus infections. The main focus is on the Big Three: human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV). Ample anti-HIV drugs are currently available in the clinic and the development of an effective combination therapy has dramatically improved the lifespan and quality of life of infected individuals. A similar trend can already be recognized for HBV and HCV: the development of multiple (directly acting) antiviral drugs and plans to control or even cure the infection. However, approaches that help prevent infection, or which provide long-lasting treatment (such as a cure) remain important goals. Immunization through gene transfer vehicles encoding immunogenic viral proteins shows promise in preventing infections with complex, highly variable, viruses such as HIV-1 or HCV. Gene therapy applications for virus infections have been discussed since the early 1990's. Whereas a true cure seems difficult to achieve for HIV-1 due to its intrinsic property to deposit its genome into that of the host, such attempts may be within reach for HCV where spontaneous viral clearance occurs in a small percentage of the infected individuals. The prospect of original gene therapy approaches may provide alternative ways to reach the same endpoint by, for example, silencing of CCR5 expression post-transcriptionally. Many alternative antiviral strategies have been developed based on a variety of novel molecular methods: e.g. ribozymes. Some studies have progressed towards pre-clinical animal models and a few antiviral gene therapies have progressed towards clinical trials. This book provides an overview of this rapidly progressing field, while focusing on the interface of gene therapy and immunology/vaccinology.

A distinguished panel of world authorities reviews the current state of today's understanding, diagnosis, and treatment of pancreatic cancer. Their cutting-edge reviews discuss both medical and surgical modalities and include numerous insights into the basic molecular processes underlying the disease. Among the key topics covered are the prospects for early diagnosis using molecular techniques, the latest diagnostic and therapeutic methods, the role of laparoscopy (diagnostic and therapeutic), and nonsurgical treatment. The reviewers also address the future possibilities for clinical advances, quality of life concerns, and the value of the Japanese "extended Whipple resection." Pancreatic Cancer will become the new standard reference for all clinicians who diagnose and treat this disease, as well as for basic scientists needing a summary of the many recent advances.
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