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

Analyzing Longitudinal Clinical Trial Data: A Practical Guide provides practical and easy to implement approaches for bringing the latest theory on analysis of longitudinal clinical trial data into routine practice.The book, with its example-oriented approach that includes numerous SAS and R code fragments, is an essential resource for statisticians and graduate students specializing in medical research. The authors provide clear descriptions of the relevant statistical theory and illustrate practical considerations for modeling longitudinal data. Topics covered include choice of endpoint and statistical test; modeling means and the correlations between repeated measurements; accounting for covariates; modeling categorical data; model verification; methods for incomplete (missing) data that includes the latest developments in sensitivity analyses, along with approaches for and issues in choosing estimands; and means for preventing missing data. Each chapter stands alone in its coverage of a topic. The concluding chapters provide detailed advice on how to integrate these independent topics into an over-arching study development process and statistical analysis plan.

This contributed volume explores how data mining, machine learning, and similar statistical techniques can analyze the types of problems arising from Traditional Chinese Medicine (TCM) research. The book focuses on the study of clinical data and the analysis of herbal data. Challenges addressed include diagnosis, prescription analysis, ingredient discoveries, network based mechanism deciphering, pattern-activity relationships, and medical informatics. Each author demonstrates how they made use of machine learning, data mining, statistics and other analytic techniques to resolve their research challenges, how successful if these techniques were applied, any insight noted and how these insights define the most appropriate future work to be carried out. Readers are given an opportunity to understand the complexity of diagnosis and treatment decision, the difficulty of modeling of efficacy in terms of herbs, the identification of constituent compounds in an herb, the relationship between these compounds and biological outcome so that evidence-based predictions can be made. Drawing on a wide range of experienced contributors, Data Analytics for Traditional Chinese Medicine Research is a valuable reference for professionals and researchers working in health informatics and data mining. The techniques are also useful for biostatisticians and health practitioners interested in traditional medicine and data analytics.

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

This timely book covers the need to know clinical practices for all those involved in molecular laboratory science. The field of molecular medicine is evolving at an astounding speed. Propelled by the new insights and technologies, advances are being made at an unprecedented rate. With dual measure given to today's breakthroughs, this book is a collection of the most current practices relevant to the clinical molecular laboratorian. It begins with an introductory section on techniques and procedure. It then presents four separate sections on infectious disease, oncology, pre/post-natal, and identity testing, with specific chapters clearly outlining clinical protocols used in daily practice. Modern Clinical Molecular Techniques cuts to the heart of what is essential for the practicing molecular laboratory scientist. It is an outstanding resource for those operating within or looking to set up a clinical molecular laboratory.

This book will compile a collection of chapters dedicated to varied aspects of PPPM in neuropsychiatric and neurodegenerative diseases. Among the topics to be covered are:
Recent advances in ALS research
News about Clinical aspects and advanced therapy approaches in personalized treatment of ALS Schizophrenia: New treatments and clinical aspects
Predictive, Preventive and Personalised Medicine in aging macular degeneration
Advances in Multiple Sclerosis Pharmacogenetics, Tailoring Treatment Efficacy, Safety and Regimen Selection
Multiple sclerosis related biomarkers: perspectives for clinical application
Preventive clinical trials in brain aging: new trends & the need of guidelines
MCI_ clinical guidelines in early diagnosis of dementia
Alzheimer's disease: diagnostics, prognostics and the road to prevention
Biomarkers for early diagnosis of Parkinson's and Alzheimer's diseases
Synucleinopathies, tauopathies, TDP-43 proteinopathies and amyloidosis PSP, MSA and other parkinsonisms

FUNDAMENTALS OF BIOSTATISTICS leads you through the methods, techniques, and computations of statistics necessary for success in the medical field. Every new concept is developed systematically through completely worked out examples from current medical research problems.

As our knowledge about arterial disease is greatly expanding, the aim of this book is to explore all aspects of arterial pathology, including classification, clinical manifestations, pathogenesis, and therapeutic options. The discussion of pathophysiologic mechanisms of arterial disease is wide ranging, encompassing hemodynamic, metabolic, humoral, inflammatory, genetic and environmental factors. Particular emphasis is placed on recent concepts, such as: the role of age-associated arterial alterations in the initiation and progression of cardiovascular diseases in older persons, the importance of mineral metabolism-bone vascular interactions, the clinical and prognostic significance of the renal resistive index, retinal circulation, toxemia of pregnancy as an arterial disease, and the role of pulmonary/vascular interaction in pulmonary hypertension and cross-talk of macrocirculation and microcirculation in target organ involvement. Evaluation procedures are carefully explained, and the full range of currently available therapeutic options, including lifestyle modifications and pharmacologic approaches, are described and appraised.

There is no single truth regarding the recognition and management of IBD. In this regards the old dictum "there is no disease but the patient" should be the golden rule. Nowadays, more complicated Crohn's disease cases at relatively young ages are not unusual. Various clinical and extraintestinal manifestations have been seen rarely until now. The evolution of the therapeutic armamentarium is now a double-edged sword since "more drugs" may mean "more side-effects, less compliance and a more critical attitude of health authorities towards the cost of treatment". Education of the patient and the family, creation of empathy and a positive rapport with the patient and a careful analysis of confounding/contributing factors to the disease behaviour are essential elements of optimal therapy of IBD patients. This book contains the proceedings of Falk Symposium 159, entitled IBD 2007 -- Achievements in Research and Clinical Practice, held in Istanbul, Turkey, on May 4--5, 2007, where opinion leaders with worldwide reputations discuss IBD and related issues in a less well-known part of the world with respect to prevalence, disease behaviour and patient characteristics, as well as the difficulties faced in differential diagnosis and management.

This edited reflects the current state of knowledge about the role of microRNAs in the formation and progression of solid tumours. The main focus lies on computational methods and applications, together with cutting edge experimental techniques that are used to approach all aspects of microRNA regulation in cancer. We are sure that the emergence of high-throughput quantitative techniques will make this integrative approach absolutely necessary in the near future. This book will be a resource for researchers starting out with cancer microRNA research, but is also intended for the experienced researcher who wants to incorporate concepts and tools from systems biology and bioinformatics into his work. Bioinformaticians and modellers are provided with a general perspective on microRNA biology in cancer, and the state-of-the-art in computational microRNA biology.

Organic chemistry research has moved rapidly toward synthesis and medicinal application of nitrogen-containing compounds such as triazenes, triazines, and hydroxytriazenes due to their excellent biological activities. Many of them are presently in clinical trials. Triazene compounds have excellent medicinal properties and limited toxicity. Hydroxytriazenes are excellent chelating agents for transition metals. Newer studies show very promising biological and medicinal applications of these classes of compounds. Hydroxytriazenes and Triazenes: The Versatile Framework, Synthesis, and Medicinal Applications highlights synthetic methods, recent advances, and potential applications of triazines, triazenes, and hydroxytriazenes. This book includes holistic information on synthetic methods for novel compounds based on this moiety, up-to-date information on the how and why of their diverse or even multitargeted medicinal application, and future state of the art of both aspects. Other features include: Highlights recent advances and diverse possible applications of biological functions Covers the chemistry of triazine, triazene, and hydroxytriazene systems On the basis of in silico predictions, the book highlights synthetic methods and their applications A valuable source of information for those actively engaged in medicinal chemistry, drug discovery, and synthetic organic chemistry

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

In recent years, molecular imaging techniques have grown to be invaluable tools for molecular biology research and, to a more modest extent, clinical medicine. In Molecular Imaging: Methods and Protocols, expert researchers explore the latest advances in the field, describing a rich variety of practical procedures and methods for diverging imaging technologies. Chapters are divided into sections that cover the imaging of basic molecular and biochemical events, imaging in pre-clinical settings, and imaging in clinical settings. Composed in the highly successful Methods in Molecular Biology(TM) series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Comprehensive and ground-breaking, Molecular Imaging: Methods and Protocols is an essential handbook for students, established practitioners, and research fellows alike.

Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get assembled to generate such specificity? In order to answer this question, we need to understand how receptors and their signalling partners are synthesized, folded and quality-controlled in order to generate functional proteins. Then, we need to understand how each partner of the signalling complex is selected to join a complex, and what makes this assembly possible. GPCRs are known to be able to function as oligomers, what drives the assembly into oligomers and what will be the effects of such organization on specificity and efficacy of signal transduction. Once the receptor complexes are assembled, they need to reach different locations in the cell; what drives and controls the trafficking of GPCR signalling complexes. Finally, defects in synthesis, maturation or trafficking can alter functionality of GPCRs signalling complexes; how can we manipulate the system to make it function normally again? Pharmacological chaperones may just be part of the answer to this question.

First published in 1986, this landmark text is the definitive guide to clinical trials, written by one of the leading experts in the field. This fully-updated second edition continues to be the most authoritative reference text on randomized clinical trials. It contains a wealth of practical information on the design, conduct, and analysis of both single center and multicenter trials. No other book on clinical trials offers as much detail on such issues as sample size calculation, stratification and randomization, data systems design, development of consent forms, publication policies, preparation of funding requests, and reporting procedures. While the basics of design, conduct, and analysis of clinical trials remain the same, there have been significant changes since the first edition of Clinical Trials was published two decades ago. In this new edition, the author discusses the refinements and improvements made to methods and procedures, changes in the policies and guidelines underlying trials, as well as requirements for registration of trials. He also discusses current practices for data sharing, for gender representation, for treatment effects monitoring, and for ethical standards of clinical trials. The importance of the randomized controlled trial has grown significantly over time and they are now the cornerstone of all evidence-based medicine. Still rich in tables, checklists, charts, and other resources for the trialist, the second edition of Clinical Trials is an indispensable reference for clinicians, biostaticians, epidemiologists, and anyone involved in the design and implementation of a clinical trial.

This timely book provides a succinct summary of methods for the synthesis of bioactive heterocycles using a multicomponent reaction (MCR) approach. The majority of pharmaceuticals and biologically active agrochemicals are heterocycles while countless additives and modifiers used in industrial applications are heterocyclic in nature. With the recent introduction of high-throughput biological evaluation, the importance of MCRs for drug discovery has been recognized and considerable efforts have been focused especially on the design and development of multi-component procedures for the generation of various bioactive heterocycles due to their significant therapeutic potential.

The study of carbonic anhydrase has spanned multiple generations of scientists. Carbonic anhydrase was first discovered in 1932 by Meldrum and Roughton. Inhibition by sulfanilamide was shown in 1940 by Mann and Keilin. Even Hans Krebs contributed to early studies with a paper in 1948 showing the relationship of 25 different sulfonamides to CA inhibition. It was he who pointed out the importance of both the charged and uncharged character of these compounds for physiological experiments. The field of study that focuses on carbonic anhydrase (CA) has exploded in recent years with the identification of new families and isoforms. The CAs are metalloenzymes which are comprised of 5 structurally different families: the alpha, beta, gamma, and delta, and epsilon classes. The alpha class is found primarily in animals with several isoforms associated with human disease. The beta CAs are expressed primarily in plants and are the most divergent. The gamma CAs are the most ancient. These are structurally related to the beta CAs, but have a mechanism more similar to the alpha CAs. The delta CAs are found in marine algae and diflagellates. The epsilon class is found in prokaryotes in which it is part of the carboxysome shell perhaps supplying RuBisCO with CO2 for carbon fixation. With the excitement surrounding the discovery of disease-related CAs, scientists have redoubled their efforts to better understand structure-function relationships, to design high affinity, isotype-specific inhibitors, and to delineate signaling systems that play regulatory roles over expression and activity. We have designed the book to cover basic information of mechanism, structure, and function of the CA families. The authors included in this book bring to light the newest data with regard to the role of CA in physiology and pathology, across phylums, and in unique environmental niches.

This book provides the most up-to-date review on new mechanisms and provides exciting insights into how heat shock proteins modulate the hosts' immune response. Written by leaders in the field of heat shock protein immunobiology, the chapters systematically and in a step-wise fashion take the reader through the fascinating sequence of events by which heat shock proteins activate immune responses and provide answers as to its biological significance to the host. From the early stages of binding and receptors-mediated signalling, to new paradigms by which heat shock proteins are released into the circulation, to antigen processing and presentation, and finally to the immune response itself this book is a must read for graduate and postgraduates in the field of Biology (plant and mammal), Biochemistry (pro- and eukaryotic), Immunology, Microbiology, Exercise Medicine, Physiology, Inflammatory diseases, Autoimmunity, Pharmacology and Pathology.

In this era of finite budgets, healthcare rationing, medication shortages, and the global aging and burgeoning of populations, numerous stakeholders in the healthcare arena must understand the basic principles of pharmacoeconomics and how these may be correctly applied to facilitate drug development, rationing, patient segmentation, disease management, and pricing model development. Pharmacoeconomics: From Theory to Practice, Second Edition focuses on how to more efficiently and rationally leverage these healthcare resources, not by restricting access to necessary services, but by using them more efficiently. This updated volume arms decision makers with the tools they need to make wise choices in an area where the stakes are extremely high-the health of the global population. Key Features: Introduces the major concepts and principles of Pharmacoeconomics Gives updated information about pharmacoeconomic models, value-based pricing, novel modelling methodologies and international utilization of these modalities in government, the pharmaceutical industry, and health care settings Demonstrates the full range of ethical and moral issues, as well as overall public health and commercial concerns that are often involved in decisions entailing pharmacoeconomic issues Presents both theory and methodology discussions, including real-world examples, in each chapter 'The methods and application of pharmacoeconomics are rapidly evolving, so the new edition of this textbook is very timely. It provides an excellent introduction for those new to the field, whether they be students, professionals within the pharmaceutical industry, or health care professionals more generally. A particularly useful feature of the book is that it gives an introduction both to the main methods used in pharmacoeconomics studies and how these studies are used in decisions about the reimbursement or appropriate use of medicines in several countries.' - Michael Drummond, Professor of Health Economics, University of York

This is the second edition of a very well received book that details how the sumoylation system functions and how it modulates numerous cellular activities. SUMO is a post-translational modifier in the ubiquitin super-family that has gained recognition over the last twenty years as an essential and prevalent regulatory molecule. Individual chapters explore the biochemistry, molecular biology, and cell biology of the sumoylation system and its substrate proteins. The book is divided into three themed parts: Molecular Functions (I), Cell Growth Regulation (II), and Diseases (III). Parts I and II focus on the contribution of sumoylation to cellular activities in both the nuclear and cytoplasmic compartments. The nuclear activities covered include nucleic acid metabolism (both RNA and DNA), chromosome structure and replication, and nucleocytoplasmic transport. Cytoplasmic processes presented include regulation of membrane ion channels, general metabolism, and apoptotic signalling. Topics in Part III include the role of sumoylation in developmental abnormalities (craniofacial and cardiovascular), diabetes, neurodegenerative diseases, cancer, and infections with viruses and bacteria. Each of the corresponding chapter authors is an active researcher who has made significant contributions to understanding sumoylation. This second edition provides updates and revisions to most of the original chapters plus adds six new chapters to address important developing areas of sumoylation research. This volume is intended for a scientific audience from undergraduates to independent researchers. The content will serve as both a solid introduction for the novice reader and an in depth treatment for the advanced scholar.

For decades now, treatment for cancer has been limited to radiation, chemotherapy, surgery, and herbal remedies--all of which offering only a small measure of hope for recovery. Now, however, there may be another option with even better results. Author Anthony J. Luksas, PhD, has dedicated over fifty years to research for not just a treatment, but a cure. His decades in the field have led him to the discovery of the ages: a road map to a cure for cancer using DNA.

Since its discovery in 1953 by Watson and Crick, the DNA double helix has been thought of as the language of God. From that point on, throughout the ensuing decades, research has decoded much of that language, giving scientists a more respectable insight into the paradox of life itself. Now, furthering that insight, Dr. Luksas has determined a means of using that language to address cancer and perhaps other diseases.

Providing a wealth of information on DNA and how it functions in the body, as well as other processes important to the replication of cancerous bodies such as cell respiration and metastasis, Dr. Luksas explains his findings with the common reader in mind.

This second edition features updated information on a variety of topics including: rat genetics and genomics, both spontaneous and induced disease; state-of-the-art technology for housing and husbandry; occupational health, and experimental models. A premier source of information on the laboratory rat that will be of interest to veterinary and medical students, senior graduate, graduate students, post-docs and researchers who utilize animals in biomedical research.
* At least 50% new information than first edition
* Includes topics on rat genetics and genomics, occupational health, and experimental models
* The premier source of information on the laboratory rat

Interval-Censored Time-to-Event Data: Methods and Applications collects the most recent techniques, models, and computational tools for interval-censored time-to-event data. Top biostatisticians from academia, biopharmaceutical industries, and government agencies discuss how these advances are impacting clinical trials and biomedical research. Divided into three parts, the book begins with an overview of interval-censored data modeling, including nonparametric estimation, survival functions, regression analysis, multivariate data analysis, competing risks analysis, and other models for interval-censored data. The next part presents interval-censored methods for current status data, Bayesian semiparametric regression analysis of interval-censored data with monotone splines, Bayesian inferential models for interval-censored data, an estimator for identifying causal effect of treatment, and consistent variance estimation for interval-censored data. In the final part, the contributors use Monte Carlo simulation to assess biases in progression-free survival analysis as well as correct bias in interval-censored time-to-event applications. They also present adaptive decision making methods to optimize the rapid treatment of stroke, explore practical issues in using weighted logrank tests, and describe how to use two R packages. A practical guide for biomedical researchers, clinicians, biostatisticians, and graduate students in biostatistics, this volume covers the latest developments in the analysis and modeling of interval-censored time-to-event data. It shows how up-to-date statistical methods are used in biopharmaceutical and public health applications.

The microfluidic lab-on-a-chip allows scientists to conduct chemical and biochemical analysis in a miniaturized format so small that properties and effects are successfully enhanced, and processes seamlessly integrated. This microscale advantage translates into greater sensitivity, more accurate results, and better information. Microfluidic Lab-on-a-Chip for Chemical and Biological Analysis and Discovery focuses on all aspects of the microfluidic lab-on-a-chip technologies and offers an overview of the available technology, its limitations, and its breakthroughs over the years. It emphasizes analytical applications of microfluidic technology and offers in-depth coverage of micromachining methods, microfluidic operations, chemical separations, sample preparation and injection methods, detection technology, and various chemical and biological analyses. Other topics of interest include the use of polymeric chips, fluid flow valve and control, single-cell analysis, DNA and RNA amplification techniques, DNA hybridization, immunoassays and enzymatic assays. Originally conceived as a single chapter published in Ewing's Analytical Instrumentation, this book is a gateway to the vast literature and conference proceedings on the topic. Microfluidic Lab-on-a-Chip for Chemical and Biological Analysis and Discovery expands upon its roots to present a comprehensive treatment of microfluidic lab-on-a-chip methods and applications for novices and advanced researchers alike.

The new age of biologic treatment of the ACL is coming. In The ACL Handbook: Knee Biology, Mechanics, and Treatment, the authors cover the past and current state of ACL injuries and treatment, and then introduce and explain the key concepts for understanding the new biologic approach to ACL treatment. The use of factors to enhance graft healing are reviewed, as well as an in-depth review of the science of platelet-rich plasma and its cellular components (platelets, white cells, and plasma). Chapters on in vitro models for science as well as the advantages and disadvantages of animal models for ACL research are included, as are chapters on the new technique of bio-enhanced ACL repair. All are discussed in easily readable text aimed at anyone with an interest of what is coming next in ACL surgery.