Several years ago, when the discovery of catalytic RNA was recognized in a public manner,many people asked if new ?elds of therapy would soon be available. Although some tentative positive answers were given,nobody would say with certainty that RNA of various kinds was a truly promising means of altering gene expression. In fact,over the past decade,both our knowledge of RNAs with different functions and the utility of RNA in the inhibition or enhancement of gene expression have occurred with great drama. We proceeded in terms of possible therapeutic tools from RNase P and group I introns through "hammerhead" RNA enzymes, antisense technology, and more recently, to RNAi and its derivatives. A useful practical method of RNA delivery in animals will complete the picture. The diversity of RNA and the varied role of it inside cells and in therapy should be a tremendous challenge for young molecular biologists. This volume will make their task easier. Sidney Altman Sterling Professor of Molecular,Cellular & Devel- mental Biology,Nobel Laureate Department of Molecular,Cellular and Developm- tal Biology Yale University V NGTPR 4/23/05 1:00 PM Page VI VI Foreword Delivery of nucleic acids to cells in an animal remains a challenging problem. It is the major obstacle to success of therapeutic approaches using genes and oli- nucleotides,including siRNAs. Solutions found so far by chemists are satisfactory only for transfection of cells in culture.

This book discusses 'how' to respectfully and responsibly include pregnant women in clinical research. In sharp contrast, the existing literature predominantly focuses on the reasons 'why' the inclusion of pregnant women in clinical research is necessary - viz., to develop effective treatments for women during pregnancy, to promote fetal safety, to reduce harm to women and fetuses from suboptimal care, and to allow access to the benefits of research participation. This book supports the shift to a new default position, whereby pregnant women are included in clinical research unless researchers argue convincingly for their exclusion. This shift raises many as yet unexplored ethical and policy questions about existing barriers to the equitable inclusion of pregnant women in research. This book is original in three key ways. First, it presents an unparalleled depth of analysis of the ethics of research with pregnant women, bringing together many of the key authors in this field as well as experts in research ethics and in vulnerability who have not previously applied their work to pregnant women. Second, it includes innovative theoretical work in ethics and disease specific case studies that highlight the current complexity and future challenges of research involving pregnant women. Third, the book brings together authors who argue both for and against including more pregnant women in formal clinical trials.

The book represents a comprehensive review and synthesis of the biomedical literature that spans over a half-century on a single protein called glyceraldehyde 3-phosphate dehydrogenase (or, GAPDH). Due to the protein's involvement in a vast array of cellular activities, GAPDH is of interest to the cell biologist, immunologist, virologist, biochemist etc. The protein has a significant role in fertility, cancer and neurodegeneration, suggesting that this book can be a vital resource for drug development. GAPDH function may provide insight into anesthesia. Furthermore, GAPDH is highly conserved meaning that the protein found in microorganisms, such as pathogens, remained relatively unchanged in evolution. Pathogens use GAPDH as a virulence factor, offering a unique challenge in developing anti-microbial agents that target this protein. To the evolutionary biologist, a book on the multi-functionality of GAPDH provides a focal point for a cogent discussion on the very origin of life.

This work provides descriptions, explanations and examples of the Bayesian approach to statistics, demonstrating the utility of Bayesian methods for analyzing real-world problems in the health sciences. The work considers the individual components of Bayesian analysis.;College or university bookstores may order five or more copies at a special student price, available on request from Marcel Dekker, Inc.

Quantitative ultrasound (QUS) of bone is a relatively recent research field. The research community is steadily growing, with interdisciplinary branches in acoustics, medical imaging, biomechanics, biomedical engineering, applied mathematics, bone biology and clinical sciences, resulting in significant achievements in new ultrasound technologies to measure bone, as well as models to elucidate the interaction and the propagation of ultrasonic wave in complex bone structures. Hundreds of articles published in specialists journals are accessible from the Web and from electronic libraries. However, no compilation and synthesis of the most recent and significant research exist. The only book on QUS of bone has been published in 1999 at a time when the propagation mechanisms of ultrasound in bone were still largely unknown and the technology was immature. The research community has now reached a critical size, special sessions are organized in major international meetings (e.g., at the World Congress of Biomechanics, the annual meetings of the Acoustical Society of America, International Bone Densitometry Workshop, etc...). Consequently, the time has come for a completely up to date, comprehensive review of the topic. The book will offer the most recent experimental results and theoretical concepts developed so far and is intended for researchers, graduate or undergraduate students, engineers, and clinicians who are involved in the field. The central part of the book covers the physics of ultrasound propagation in bone. Our goal is to give the reader an extensive view of the mathematical and numerical models as an aid to understand the QUS potential and the types of variables that can be determined by QUS in order to characterize bone strength. The propagation of sound in bone is still subject of intensive research. Different models have been proposed (for example, the Biot theory of poroealasticity and the theory of scattering have been used to describe wave propagation in cancellous bone, whereas propagation in cortical bone falls in the scope of guided waves theories). An extensive review of the models has not been published so far. We intend in this book to present in details the models that are used to solve the direct problem and strategies that are currently developed to address the inverse problem. This will include analytical theories and numerical approaches that have grown exponentially in recent years. Most recent experimental findings and technological developments will also be comprehensively reviewed.

A thoroughly revised and updated collection readily reproducible techniques for culturing human cells. This new edition includes a wide range of human cell types relevant to human disease and new chapters on fibroblasts, Schwann cells, gastric and colonic epithelial cells, and parathyroid cells. The protocols follow the successful Methods in Molecular Medicine (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

In recent years, serine proteases and matrix metalloproteinases (MMPs) have gained considerable attention in tumor biology. For most of these proteases, their expression is a reliable indication of ongoing tissue remodeling. This book provides a comprehensive evaluation of the mechanisms of action of proteases and their inhibitors in tumor biology. The first part provides the reader with a selective overview of the molecular biology of serine proteases, MMPs and their physiological inhibitors. The most important proteases and their physiological as well as synthetic inhibitors are evaluated in the most relevant models of experimental and human cancer. The clinical aspects are also taken into account.
This volume offers an update on this challenging aspect of cancer treatment, its interest bias, and possible clinical implication.

Prediction models are important in various fields, including medicine, physics, meteorology, and finance. Prediction models will become more relevant in the medical field with the increase in knowledge on potential predictors of outcome, e.g. from genetics. Also, the number of applications will increase, e.g. with targeted early detection of disease, and individualized approaches to diagnostic testing and treatment. The current era of evidence-based medicine asks for an individualized approach to medical decision-making. Evidence-based medicine has a central place for meta-analysis to summarize results from randomized controlled trials; similarly prediction models may summarize the effects of predictors to provide individu- ized predictions of a diagnostic or prognostic outcome. Why Read This Book? My motivation for working on this book stems primarily from the fact that the development and applications of prediction models are often suboptimal in medical publications. With this book I hope to contribute to better understanding of relevant issues and give practical advice on better modelling strategies than are nowadays widely used. Issues include: (a) Better predictive modelling is sometimes easily possible; e.g. a large data set with high quality data is available, but all continuous predictors are dich- omized, which is known to have several disadvantages.

The number of, and interest in, quality of life studies has grown dramatically in the last decade. On an ever increasing basis, patients, clinicians, researchers, and health policy regulators are considering quality of life in assessing treatment alternatives. Unfortunately, most discussions of quality of life are narrow in scope -- applying to only one disease group. This unique book represents the concerted effort of experts in academia, federal government health care regulators, and pharmaceutical industry representatives to define the promise and the problems associated with quality of life studies. The issues covered range from cross cutting ones to those that are specific to particular illnesses.
Because quality of life takes into consideration such domains as mood, vocation, family, sexual functioning, social participation, and costs, this book will serve as an invaluable companion to readers with an interest in behavioral medicine research.

This book covers the wide set of well-regulated virulence factors and defense mechanisms of Pseudomonas aeruginosa focusing on stress responses and the evolution of this opportunistic human pathogen. Pseudomonas aeruginosa is responsible for one out of ten hospital infections. Additionally, this Gram-negative bacterium is accountable for persistent infections in immunocompromised individuals and the leading cause of chronic lung infections in cystic fibrosis patients. This book provides insight on the metabolic versatility of Pseudomonas aeruginosa and its mechanisms for biofilm formation that make this organism highly efficient in causing infections. The book invites the readers to learn more about the intrinsic ability of Pseudomonas aeruginosa to resist a wide variety of antimicrobial agents due to the concerted action of multidrug efflux pumps, antibiotic-degrading enzymes, and the low permeability of bacterial cellular envelopes. Particular focus is put on the evolutionary role of different types of protein-secretion systems in pathogenesis, flagella and their role in chemotaxis and surface sensing, and host-pathogen interactions. This book is a useful introduction to the field for junior scientists interested in the biology and pathogenesis of Pseudomonas aeruginosa. It is also an interesting read for advanced scientists and medical specialists working within this field, providing a broader view of the topic beyond their specific area of specialization.

This book deals with pathophysiology and pharmacology of spontaneously hypertensive rats (SHR) and describes new trends in SHR research from hemodynamic characteristics to immunological views. It is devoted to the use of tissue culture studies to elaborate SHR characteristics.

This detailed volume explores the application of multiplex biomarker methods in the critical area of COVID-19 research through state-of-the-art technologies in the fields of genomics, proteomics, transcriptomics, metabolomics, and imaging. The book features a series of protocols from labs across the globe employing multiplex molecular approaches, which can be applied to accelerate progress in the research of SARS-CoV-2 and other infectious illnesses. 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 essential, Multiplex Biomarker Techniques: Methods and Applications for COVID-19 Disease Diagnosis and Risk Stratification serves as a vital resource for researchers in the areas of virology, metabolic diseases, respiratory disorders, as well as to clinical scientists, physicians, pharmacologists, and the healthcare services.

The 1st World Congress on Geriatrics and Neurodegenerative Disease Research (GeNeDis 2014), will focus on recent advances in geriatrics and neurodegeneration, ranging from basic science to clinical and pharmaceutical developments and will provide an international forum for the latest scientific discoveries, medical practices and care initiatives. Advanced information technologies will be discussed concerning the various research, implementation and policy, as well as European and global issues in the funding of long-term care and medico-social policies regarding elderly people. GeNeDis 2014 takes place in Corfu Greece, 10-13 April 2014. This volume focuses on the sessions from the conference on computational biology and bioinformatics.

This volume investigates the links between the incidence of diet-related cancers and dietary patterns within Europe. It presents current understanding of the major cancers thought to be caused by diet alongside detailed data on regional variations in dietary composition, and collates these sets of information to illustrate associations between foods and nutrients and the risk of cancer at specific sites. There is particular discussion of the role of fat, meat, fibre, cereals and fresh vegetables. The importance of the "Mediterranean diet", and regional variance in this diet within Europe, is examined. Japanese and US dietary evidence is also considered. This book highlights the debate on cancer and diet, and points the way ahead for important new research.

This book focuses on leadership and management strategies including project management, budget planning and management, governance, building a team, and developing a strategy for successful recruitment. Many creative arts therapy researchers lack training and experience in designing and implementing large scale high impact clinical trials. This book is the first in the creative arts therapies that provides guidance on clinical trial implementation. Data management, monitoring, and intervention fidelity and development of a statistical analysis plan are outlined. Finally, the text explores development of a dissemination plan as well as how to commercialise research.

This book gives an overview of therapeutic drug monitoring (TDM) and its clinical application. It also highlights recent advances in toxicological studies, as they relate to therapeutic drug monitoring. This is one of the few books available on the market that covers TDM. Therapeutic drug monitoring (TDM) is a clinical decision-making tool that enables dosage regimen adjustments based on clinical and laboratory measurements. TDM not only involves the measuring of drug concentrations but also interpretation of the results. There is a strong correlation between drug concentrations in body fluids and outcome than between dose and outcome. The chapters include coverage of analytical techniques, pharmacokinetics, therapeutic indices, artificial intelligence and recent advances in toxicological studies. The book fills a gap in published literature and provides reliable information on; Analytical techniques in TDM and clinical toxicology TDM and pharmacokinetic studies TDM of drugs with narrow therapeutic indices Artificial intelligence in TDM and clinical toxicology Future directions and challenges

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.

'I am blown away by the level of detail Phil Cavell brings to his work.' - Elinor Barker MBE, multiple world champion and Olympic gold medallist 'The Midlife Cyclist is a triumph' - Cycling Plus 'An amazing accomplishment... a simple-to-understand precis of your midlife as a cyclist - you won't want to put it down.' - Phil Liggett, TV cycling commentator 'Phil is eminently qualified to write The Midlife Cyclist. Well, he is certainly old enough.' - Fabian Cancellara, Tour de France rider and two-time Olympic champion Renowned cycling biomechanics pioneer, Phil Cavell, explores the growing trend of middle-aged and older cyclists seeking to achieve high-level performance. Using contributions from leading coaches, ex-professionals and pro-team doctors, he produces the ultimate manifesto for mature riders who want to stay healthy, avoid injury - and maximise their achievement levels. Time's arrow traditionally plots an incremental path into declining strength and speed for all of us. But we are different to every other generation of cyclists in human history. An ever-growing number of us are determined to scale the highest peaks of elite physical fitness into middle-age and beyond. Can the emerging medical and scientific research help us achieve the holy triumvirate of speed and health with age? The Midlife Cyclist offers a gold standard road-map for the mature cyclist who aims to train, perform and even race at the highest possible level.

This book contains original essays that look at contagious/infectious disease pandemics and the ethical public policy and administration these have entailed. In particular, the pandemics of the 1918 flu pandemic, HIV in the 1990s, SARS in 2003, Ebola from 2014-2016 and the novel COVID-19 in 2020 are highlighted. The contributions in this work offer the reader insights in these and several other recent pandemics that present differently-either via contagion or mortality rate-and how each should be addressed by countries of various sorts. This book is a must for the ongoing debate on how we should treat public health crises, such as the one we have all just encountered in the novel COVID-19 pandemic.

A comprehensive collection of readily reproducible methods for studying receptors in silico, in vitro, and in vivo. These cutting-edge techniques cover mining from curated databases, identifying novel receptors by high throughput screening, molecular methods to identify mRNA encoding receptors, radioligand binding assays and their analysis, quantitative autoradiography, and imaging receptors by positron emission tomography (PET). Highlights include phenotypic characterization of receptors in knockout mice, imaging receptors using green fluorescent protein and fluorescent resonance energy transfer, and quantitative analysis of receptor mRNA by TaqMan PCR. These book equips the researcher with techniques for exploring the unprecedented number of new receptor systems now emerging and the so-called "orphan" receptors whose activating ligand has not been identified.

This fully revised new edition explores advances in the prevention and treatment of oral diseases. Beyond the updated chapters, the book delves into regenerative biology, gene editing and the use of CRISPR in oral biology, as well as histone acetylation and deacetylation methods, further reflecting advances in the application of molecular techniques to oral biology. 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 and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Oral Biology: Molecular Techniques and Applications, Third Edition serves as an ideal basic resource not only for new researchers but also for experienced scientists wishing to expand their research platform into new areas of this vital field.

In the post human-genome project era, cancer specific genomic maps are redesigning tumor taxonomy by evolving from histopathology to molecular pathology. The success of a cancer drug today is fundamentally based on the success in identifying target genes that control beneficial pathways. The overwhelming power of genomics and proteomics has enlightened researchers about the fact that the PI3K-mTOR pathway is the most commonly up-regulated signal transduction pathway in various cancers, either by virtue of its activation downstream of many cell surface growth factor receptors or by virtue of its collateral and compensatory circuitry with RAS-MAPK pathway. Oncogenic signaling in the majority of solid tumors is sustained via the PI3K-AKT-mTOR pathway. Because of its prominent role in many cancer types, the PI3K-mTOR pathway has become a major therapeutic target. The volume includes two complementary parts which address the problem of etiology and disease progression and is intended to portray the very basic mechanisms of the PI3K-AKT-mTOR signaling pathway's involvement in various facets of the cancer, including stem cell renewal, cell metabolism, angiogenesis, genetic instability, and drug resistance. Significant progress has been made in recent years elucidating the molecular mechanism of cancer cell proliferation, angiogenesis, and drug-resistance in relation to the PI3K-mTOR pathway and this volume provides an in-depth overview of recent developments made in this area.

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 book provides an overview of the history of integrative bioinformatics and the actual situation and the relevant tools. Subjects cover the essential topics, basic introductions, and latest developments; biological data integration and manipulation; modeling and simulation of networks; as well as a number of applications of integrative bioinformatics. It aims to provide basic introduction of biological information systems and guidance for the computational analysis of systems biology. This book covers a range of issues and methods that unveil a multitude of omics data integration and relevance that integrative bioinformatics has today. It contains a unique compilation of invited and selected articles from the Journal of Integrative Bioinformatics (JIB) and annual meetings of the International Symposium on Integrative Bioinformatics.