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

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.

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

Accurate sample size calculation ensures that clinical studies have adequate power to detect clinically meaningful effects. This results in the efficient use of resources and avoids exposing a disproportionate number of patients to experimental treatments caused by an overpowered study. Sample Size Calculations for Clustered and Longitudinal Outcomes in Clinical Research explains how to determine sample size for studies with correlated outcomes, which are widely implemented in medical, epidemiological, and behavioral studies. The book focuses on issues specific to the two types of correlated outcomes: longitudinal and clustered. For clustered studies, the authors provide sample size formulas that accommodate variable cluster sizes and within-cluster correlation. For longitudinal studies, they present sample size formulas to account for within-subject correlation among repeated measurements and various missing data patterns. For multiple levels of clustering, the level at which to perform randomization actually becomes a design parameter. The authors show how this can greatly impact trial administration, analysis, and sample size requirement. Addressing the overarching theme of sample size determination for correlated outcomes, this book provides a useful resource for biostatisticians, clinical investigators, epidemiologists, and social scientists whose research involves trials with correlated outcomes. Each chapter is self-contained so readers can explore topics relevant to their research projects without having to refer to other chapters.

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

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

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

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.

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

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

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.

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.

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

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

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

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 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.

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.

Fundamental Concepts for New Clinical Trialists describes the core scientific concepts of designing, data monitoring, analyzing, and reporting clinical trials as well as the practical aspects of trials not typically discussed in statistical methodology textbooks. The first section of the book provides background information about clinical trials. It defines and compares clinical trials to other types of research studies and discusses clinical trial phases, registration, the protocol document, ethical issues, product development, and regulatory processes. It also includes a special chapter outlining the valuable attributes that statisticians can develop to maximize their contributions to a clinical trial. The second section examines scientific issues faced in each progressive step of a clinical trial. It covers issues in trial design, such as randomization, blinding, control-group selection, endpoint selection, superiority versus noninferiority, and parallel group versus crossover designs; data monitoring; analyses of efficacy, safety, and benefit-risk; and the reporting/publication of clinical trial results. As clinical trials remain the gold standard research studies for evaluating the effects of a medical intervention, newcomers to the field must have a fundamental understanding of the concepts to tackle real-world issues in all stages of trials. Drawing on their experiences in academia and industry, the authors provide a foundation for understanding the fundamental concepts necessary for working in clinical trials.

This book features multi-omics big-data integration and data-mining techniques. In the omics age, paramount of multi-omics data from various sources is the new challenge we are facing, but it also provides clues for several biomedical or clinical applications. This book focuses on data integration and data mining methods for multi-omics research, which explains in detail and with supportive examples the “What”, “Why” and “How” of the topic. The contents are organized into eight chapters, out of which one is for the introduction, followed by four chapters dedicated for omics integration techniques focusing on several omics data resources and data-mining methods, and three chapters dedicated for applications of multi-omics analyses with application being demonstrated by several data mining methods. This book is an attempt to bridge the gap between the biomedical multi-omics big data and the data-mining techniques for the best practice of contemporary bioinformatics and the in-depth insights for the biomedical questions. It would be of interests for the researchers and practitioners who want to conduct the multi-omics studies in cancer, inflammation disease, and microbiome researches.

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.