Non-vesicular intracellular cholesterol transport is an important mechanism for maintaining membrane cholesterol homeostasis. Recent reports of studies directed at soluble cholesterol transport proteins indicate that aberrant expression of the START proteins may contribute to disease states associated with disorders in cholesterol homeostasis. This is an exciting new direction in the field and the purpose of this book will be to highlight the current research directed at potential roles for the START family in diabetes, cancer, and atherogenesis. This book also provides a personal and historical perspective of the discovery-to-publication journey that the authors had for their particular START domain family member. The goal will be to provide perspectives to graduate students, post-doctoral fellows, and endocrinology fellows on the research discovery process.

This volume contains refereed papers by participants in the two weeks on Clinical Trials and one week on Epidemiology and the Environment held as part of the six weeks workshop on Statistics in the Health Sciences Applications at the Institute for Mathematics and its Applications (IMA) in the summer of 1997. Donald Berry was in charge of the weeks on clinical trials, and Elizabeth Halloran organized the week on epidemiology and the environment. The collection includes a major contribution from Jamie Robins, Andrea Rotnitzky, and Daniel Scharfstein on sensitivity analysis for selection bias and unmeasured confounding in missing data and causal and inference models. In another paper, Jamie Robins presents a new class of causal models called marginal structural models. Alan Hubbard, Mark van der Laan, and Jamie Robins present a methodology for consistent and efficient estimation of treatment-specific survival functions in observational settings. Brian Leroux, Xingye Lei, and Norman Breslow present a new mixed model for spatial dependence for estimating disease rates in small areas. Andrew Lawson and Allan Clark demonstrate Markov Chain Monte Carlo methods for clustering in spatial epidemiology. Colin Chen, David Chock, and Sandra Winkler present a simulation study examining confounding in estimation of the epidemiologic effect of air pollution. Dalene Stangl discusses issues in the use of reference priors and Bayes factors in analyzing clinical trials. Stephen George reviews the role of surrogate endpoints in cancer clinical trials.

Prominent experimentalists critically review the animal models widely used in developing powerful new therapies for central nervous system diseases. Coverage includes novel uses of animal models of Alzheimer's, Parkinson's, and Huntington's diseases, and studies of aging. Techniques that rely heavily on behavioral analyses, as well as models developed from infusions of neurotoxins and from advances in molecular biology, are thoroughly explicated, as are models developed for more acute neurological conditions, including traumatic brain injury and stroke. Comprehensive and authoritative, Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic offers neuroscientists, pharmacologists, and interested clinicians a unique survey of the most productive animal models of the leading neurological diseases currently employed to develop today's innovative drug therapies.

This edition includes both updates from the previous book titled Simulation for Designing Clinical Trials and new uses and issues concerning clinical trial simulations (CTS) along with case studies of how clinical trial simulations are being applied in various therapeutic and application areas. Importantly, the book expands on the utility of CTS for informing decisions during drug development and regulatory review. Each chapter was written by esteemed authors who have demonstrated expertise in state-of-the-art application of CTS. The target audience for this book includes not only researchers and scientists who wish to consider use of simulations in the design, analysis, or regulatory review and guidance of clinical trials, but also academic researchers and others working in drug development (e.g., clinicians, senior managers, project planning and regulatory affairs professionals). The focus is more on how the authors have used clinical trial simulation in decision processes instead of illustrating detailed technical aspects. This book is an information source that enables the reader to gain overall knowledge on how clinical trial simulations can be used to improve the efficiency, informativeness, speed and economy of model-based drug development and regulation.

This book presents a comprehensive view on mycotoxins of agricultural as well as non-agricultural environments and their health effects in humans and animals. Mycotoxins have immunosuppressive effects; but some of them can cause cancers, mutagenicity, neurotoxicity, liver and kidney damage, birth defects, DNA damage and respiratory disorders. The problem of mycotoxins is long-lasting and their direct or indirect exposures to humans and animals must be further discussed. The first chapter will cover the historical perspective of mycotoxins along with timeline while the second one will provide overview including classification of mycotoxins and mycotoxicoses. The comprehensive information/ literature on traditional, emerging and mushroom mycotoxins will be given in chapters 3, 4 and 5 respectively. Chapter 6 will deal with mycotoxins co-occurrence poisoning whereas new and masked mycotoxins will be described in chapter 7. The important aspects of mycotoxin studies like extraction, characterization and analysis and management strategies will be summarized in 8 and 9 chapters. The last chapter of the book will cover the recent developments in toxicokinetic studies of mycotoxins. The book will have the most up-to-date information and recent discoveries to deliver accurate data and to illustrate essential points to a wide range of readers including mycologists, clinicians, agricultural scientists, chemists, veterinarians, environmentalists and food scientists.

This volume focuses on the cell biology and physiology of skeletal muscle regeneration. This Book is a collection of classic and cutting edge protocols optimized for mice, but in most cases adaptable to rat or other mammalian models, that will allow an investigator to develop and implement a research study on skeletal muscle regeneration. Chapters address the three major areas of study: provoking regeneration by inducing damage to muscle, analyzing the progenitor cells of skeletal muscle, and quantifying overall muscle function. Subjects discussed include: inducing skeletal muscle injury by eccentric contraction; volumetric muscle loss; single myofiber isolation and culture; satellite cell transplantation; muscle clearing for whole mount immunostaining; luciferase tracking of muscle stem cells; mitochondrial and mitophagy flux analysis; in vivo assessment of muscle contractility; force measurements on single isolated myofibers; and analysis of aerobic respiration in intact skeletal muscle tissue by microplate respirometry. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to each respective topic, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting edge and practical, Skeletal Muscle Regeneration in the Mouse: Methods and Protocols is an essential laboratory reference for research in skeletal muscle growth, damage, repair, degeneration, and regenerative therapy in the mouse model system.

This book introduces the translational informatics applied to most aspects of virus infection, including tracking of virus origin, detection and prevention of infection, drug discovery, and vaccine design as well as smart city-level monitoring and controlling of the virus epidemic by government. It covers the informatics for data mining and modelling at molecular, tissue/organ, individual, and population levels. The informatics for immunological mechanisms and the personalized prediction and treatment of infected patients are also summarized. The perspectives on the application of artificial intelligence to the prevention of virus outbreaks are also given. This book will be helpful to readers who are interested in prevention of virus infection, biomedical informatics, and artificial intelligence in medicine and healthcare.

This volume provides a state-of-the-art update on Fc Receptors (FcRs). It is divided into five parts. Part I, Old and New FcRs, deals with the long-sought-after FcR and the recently discovered FCRL family and TRIM21. Part II, FcR Signaling, presents a computational model of Fc RI signaling, novel calcium channels, and the lipid phosphatase SHIP1. Part III, FcR Biology, addresses major physiological functions of FcRs, their glycosylation, how they induce and regulate both adaptive immune responses and inflammation, especially in vivo, FcR humanized mice, and the multifaceted properties of FcRn. Part IV, FcRs and Disease, discusses FcR polymorphism, FcRs in rheumatoid arthritis and whether their FcRs make macaques good models for studying HIV infection. In Part V, FcRs and Therapeutic Antibodies, the roles of various FcRs, including Fc RIIB and Fc RI, in the immunotherapy of cancer and autoimmune diseases using monoclonal antibodies and IVIg are highlighted. All 18 chapters were written by respected experts in their fields, offering an invaluable reference source for scientists and clinicians interested in FcRs and how to better master antibodies for therapeutic purposes.

"Research" and "Publishing" are phrases familiar to all neurosurgeons and neuroscientists. Many young neurosurgeons struggle with them on a trial-and-error basis at first, and there are not structured education programs providing information on standard methods. The European Association of Neurosurgical Societies Research Committee has developed a course on research and publication methods for residents in neurosurgery who have not yet completed training. This supplement includes selected contributions from this course and will serve as an essential handbook providing basic tools to guide research and publication work, presenting time-saving advice, and resulting in the most beneficial contributions in experimental and clinical research.

Navigating research careers is often highly challenging for early career researchers (ECRs) in the social sciences. The ability to thrive in research careers is complex and requires "soft" people and management skills and resilience that often cannot be formally taught through university coursework. Written from a peer perspective, this book provides guidance and establishes emotional rapport on topical issues relevant for ECRs in academia and industry. The authors are ECRs who have been successful in navigating their careers, and they seek to connect with readers in a supportive and collegial manner. Each chapter includes elements of story-telling and scientific thinking and is organized into three parts: (1) a personal story that is relevant to the topic; (2) key content on professional and personal effectiveness based on evidence in the psychological, sociological, and/or management sciences; and (3) action points and practical recommendations. The topics covered are specifically curated for people considering undertaking research careers or already working in research, including: Work Hard, Snore Hard: Recovery from Work for Early Career Researchers Networking and Collaborating in Academia: Increasing Your Scientific Impact and Having Fun in the Process Accelerating Your Research Career with Open Science Engaging with the Press and Media Make Your Science Go Viral: How to Maximize the Impact of Your Research Exploring the Horizon: Navigating Research Careers Outside of Academia Thinking like an Implementation Scientist and Applying Your Research in Practice Survival Guide for Early Career Researchers summarizes relevant evidence-based research to offer advice in strategic but also supportive ways to ECRs. It is an essential go-to practical resource for PhD students, postdoctoral fellows, and junior faculty. This book will also benefit senior researchers who are serving as mentors or delivering professional development programs, administrators and educators in institutions of higher learning, and anyone with an interest in building a successful research career.

This volume details protocols on rationale design of therapeutic siRNA molecules and its encapsulation with smart vehicles to overcome the barriers to an effective administration in vivo. 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, Design and Delivery of SiRNA Therapeutics aims to ensure successful results in the further study of this vital field.

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.

Following many reports that were published in the last two decades on correlations of multiphase structures of the surface of materials with their antithrombogenicity or biocompatibility a research project ''Design of Multiphase Biomedical Materials'' was carried out in Japan between 1982 and 1986. The objective of this research project was to elucidate various aspects of biomedical behaviour of multiphase systems at the interface with living bodies at the molecular, cellular and tissue levels. Multiphase materials studied cover polymers having microphase-separated structures, hydrogels, immobilized enzymes (or cells), ceramics and metallic materials.
The research project was carried out by the following subgroups:
-- Multiphase biomedical materials with microdomain structures
-- Multiphase biomedical materials containing liquid components
-- Hybrid-type multiphase biomedical materials with biological components
-- Inorganic and metallic multiphase biomedical materials
-- Methods for analysis and evaluation of multiphase biomedical materials
This book contains the results of the research project in an edited form and aims to provoke a better understanding about various aspects of cell--material interactions in which the multiphase systems play a crucial role.

This detailed volume introduces the reader to current methods in glaucoma research, in particular those that make use of animal disease models. Given that the retinal ganglion cells damaged and destroyed by glaucoma do not regenerate after lowering the intraocular pressure, new therapeutic approaches that protect ganglion cells directly is a vital research goal that this volume's contents aim to aid scientists in developing. 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 practical, Glaucoma: Methods and Protocols serves as a useful guide for both ophthalmologists in clinical practice and researchers in the field.

This volume details the history of Retinitis Pigmentosa and current treatment options. Chapters guide readers through CRISPR, gene therapy, stem cell therapy, next-generation sequencing methods, gene editing, and translational applications of other therapies to the treatment of Retinitis Pigmentosa. 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, Retinitis Pigmentosa aims to be a useful practical guide to researches to help further their study in this field.

This detailed book focuses on cutting-edge methods for Parkinson's disease (PD) research, such as the analysis of the prion-like properties of -synuclein, mitochondrial functions related to the PINK1-Parkin pathway/CHCHD2, the endolysosome pathway related to LRRK2, VPS35, and ATP13A2 using cultured cells (including patient iPS cells), deep brain stimulation therapy, classic mitochondrial toxins related to PD, and genetic associations and screenings using mammalian and invertebrate genetic models of PD. The collection intends to serve as an introductory protocol book for basic research on PD pathogenesis. 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, Experimental Models of Parkinson's Disease is an ideal guide for researchers continuing to work toward making PD risk predictable and surmountable.

A comprehensive overview of the effects of trichloroethylene toxicity caused by real-life exposure levels highlighting how exposure to trichloroethylene may contribute to the etiology of several idiopathic human diseases. Discussion will focus on different kinds of modeling and how they may be used to predict functional consequences and to dissect the contribution of different mechanistic pathways, including potential mechanisms of action for trichloroethylene toxicity in different organ systems. It will explore the role of epigenetic alterations in trichloroethylene toxicity, this provides important mechanistic information and may also provide the basis for intervention therapy. Chapters will also explain how the risks from trichloroethylene exposure may be greater in certain populations based on genetic predisposition, age of exposure and co-exposure to other chemicals With contributions from international experts in the field, Trichloroethylene: Toxicity and Health Risks is an essential resource for researchers and clinicians in toxicology, immunology, medicine and public health as well as industry and government regulatory scientists involved in safety and health protection and epidemiologists, highlighting the need for interdisciplinary cooperation in solving issues of environmental toxicity.

This volume details a collection of laboratory protocols to study asthma in mice and humans. Chapters cover animal models of asthma, methods to measure asthma-related molecules, protocols to detect, isolate, culture and stimulate cells that contribute to asthma in mice and humans, methods to deplete these cells in vivo and study responses of intact airway tissues ex vivo. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Asthma: Methods and Protocols aims to be a foundation for future studies and to be a source of inspiration for new investigations in the field.

This volume details experimental protocols to study structure and function of hepatocytes in vivo and in vitro, and for characterizing heterogeneity and plasticity of hepatocytes in healthy and in injured liver. Chapters guide readers through separating hepatocyte subfractions, characterizing the heterogeneity, novel culture systems, hepatocyte-like cells from human pluripotent stem cells, analyzing drug metabolism, monitoring protein sorting, manipulating gene expression, and methods for expanding primary hepatoblastoma and identifying hepatocellular carcinoma subtypes. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Hepatocytes: Methods and Protocols aims to provide techniques to further understand molecular mechanisms involved in the regulating hepatocyte functions and underlying liver diseases.

* Reviews recent developments in bacterial cysteine proteases * Focuses on protozoan parasites of medical importance * Covers cysteine proteases from helminths of medical and veterinary importance Cysteine proteases expressed by pathogenic organisms play key roles in virulence including host entry, feeding and suppression of host immune responses. This book gives comprehensive coverage to all aspects of pathogen cysteine proteases and brings together numerous scientific advances which have been made over many years. Thus, the biochemistry, molecular biology and structure-function relationships of these important pathogen enzymes are covered in detail. Written by leading researchers from Europe, Australia and North America, this book is essential reading for students and professionals interested in human medicine and infectious disease research.

Colorectal cancer has for more than two decades served as the paradigm for the multi-step concept of cancer initiation and progression. Perhaps more than any other organ site, cancer of the colon is extensively characterized at the molecular level. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. The book will focus on the progression from the identification of mutations that drive colorectal cancer initiation and progression to the search for novel therapies to treat the disease.

This installment in the Techniques in Life Science and Biomedicine for the Non-Expert series aims to describe ESR spectroscopy as a tool for different applications, such as Healthcare & Pharmaceutical Science, Paleontology & Geochronology and Food Science. In keeping with the series theme, this text is presented in such a manner that the amateur researcher or graduate student can absorb it, while highlighting recent advances and applications of the field. Chapters include solved examples and questions to reinforce themes and encourage readers to apply what they've learnt.

The go-to guide to evidence-based practice in nursing for more than a decade, Evidence-Based Practice in Nursing & Healthcare: A Guide to Best Practice, 5th Edition, presents the latest perspectives on research-backed nursing practice in an engaging, user-friendly approach that has made this the bestselling resource of its kind.    AJN award-winning authors Bernadette Melnyk and Ellen Fineout-Overholt combine straightforward, conversational storytelling, inspiring quotes, and engaging case studies to make evidence-based practice accessible for students at any level of familiarity. With real-world examples and meaningful strategies in every chapter, this revised and reimagined 5th Edition gives students the confidence to meet today’s clinical challenges and ensure the most effective patient outcomes for years to come.      New to this edition: NEW! Reimagined coverage and a new chapter on applying implementation science to clinical practice settings familiarize students with the latest evidence and emerging implementation and evaluation tools.  UPDATED! Content throughout empowers you to more effectively teach evidence-based practice principles in academic and clinical settings. UPDATED! Making EPB Real case studies reinforce clinical application through real-world examples. 

Intended for students and general readers alike, this encyclopedia covers the history of human medical experimentation, for better and worse, from the time of Hippocrates to the present. Thanks to medical experiments performed on human subjects, we now have vaccines against smallpox, rabies, and polio. Yet the advances that saved lives too often involved the exploitation of vulnerable populations. Covering the history of human medical experimentation from the time of Hippocrates to today, this work will introduce readers to the topic through a mixture of essays and ready-reference materials. The book covers the experiments themselves; the people, companies, and government agencies that carried them out; the relevant medical and sociopolitical background; and the legislation and other protective measures that arose as a result. The encyclopedia is divided chronologically into six periods: pre-19th century, the 19th century, the pre-World War II 20th century, the World War II era, the Cold War era, and the post-Cold War period to today. Each period begins with an introductory essay and ends with a bibliography. Alphabetically arranged entries in each section cover pertinent people, experiments, and topics. The volume is enriched throughout with a wealth of primary sources, such as physicians' descriptions of their experiments. Medical experiments are not just a thing of the past, and readers will also learn about questions and debates related to contemporary efforts to advance medical science.

This volume provides an overview on the influence of Extracellular Matrix (ECM) on tumor progression. It covers topics such as signaling induced by structural ECM proteins including collagen and fibronectin, the control of ECM deposition and the turnover in tumors. Also discussed are the migration of cells through basement membranes and the function of proteoglycans including lumican and veriscan in tumor progression. Biomaterial-based in-vitro models as well as C. elegans models of the tumor microenvironment are used to show how these models can lead to a greater understanding of the disease mechanisms that promote cancer progression. The book addresses researchers working on cancer biology or ECM, and oncologists alike.