This volume consists of four chapters that cover a structurally diverse range of naturally occurring compounds. Chapter 1 delves into the chemistry of pyrogallols and their oxidized products, the hydroxy-o-quinones, including their role in cycloaddition reactions in the chemical synthesis of several fungal metabolites. Chapter 2 provides an in-depth description of the constituents of agarwood essential oil and smoke samples that are used in the perfumery industry, with an emphasis on the sesquiterpenoid and chromones constituents so far known. Chapter 3 discusses the defensive chemical ecology of two North American newt species that both produce tetrodotoxin, a well-known neurotoxin that causes paralysis and death in metazoans by disrupting electrical signals in the nerves and muscles. Chapter 4 discusses the limonoids and triterpenoids from the genus Walsura of the plant family Meliaceae, of which a number of species are utilized in several southeastern Asian countries in systems of folk medicine.

The book presents the latest advances in research into health effects of air pollution, with heavy motor vehicle traffic or cigarette smoke as the exemplar of pollution. The airways are the first-line defense system against pollution. The book focuses on respiratory ailments underlain by inflammation, increased susceptibility to infection, particularly acquired during harsh environmental conditions and exposures to particulate matter or pathogens. The importance of astute analysis of lung function for early diagnosis of disorders is underscored. A knowledge deficit concerning the aerosolized drug delivery through the airways also is addressed. Recent developments and viewpoints in the field of environmental health hazards as well as methodological advances in their assessment are provided. The book will be of interest to pulmonologists, healthcare providers, researchers and clinicians engaged in environment-related respiratory diseases, but also to policy makers concerned with clean ambient air quality.

This book examines a range of contemporary ideas and arguments concerning the core yet unsettled clinical issues. Important aspects of pulmonary disorders are tackled such as occupational and environmental respiratory health hazards, the role of vitamin D supplementation in airway allergy, or nutritional aspects of care for lung cancer patients. Metabolic disorders affecting the processes of atherogenesis and systemic inflammation also are tackled. Attention is directed to rare but severe pediatric disease entities. Articles give readers practice at analyzing clinical data. The practical insights emphasize the role of science in transforming biomedical knowledge and care. This volume will be essential reading for clinicians, researchers, and other healthcare professionals engaged in effective patient care and therapy.

Despite extensive physiological, biochemical, and structural studies, the mechanisms of muscle contraction operating in living muscle fibres are still not clearly understood. This book aims to describe and assess various experimental methods currently used in the field of muscle research. For
each method discussed, there is a comprehensive description of its advantages, problems, and limitations. Each chapter also contains a summary of the central results to have been obtained using each method. Comprehensively written by experts in their respective fields, this book will be of interest
to all investigators in muscle physiology.

Covering all major arthropods of medical importance worldwide, this award-winning resource has established itself as a standard reference for almost 25 years. With the globilization of commerce and the world becoming more intimately connected through the everyday ease of travel, unknown arthropod species are being increasingly encountered. This means access to up-to-date, authoritative information in medical entomology has never been more important. Now in its seventh edition, this book maintains its well-acclaimed status as the ultimate easy-to-use guide to identify disease-carrying arthropods, the common signs and symptoms of vector-borne diseases, and the current recommended procedures for treatment. Includes an in-depth chapter with diagnostic aids to help physicians to recognize and accurately diagnose arthropod-related diseases and conditions more easily Updates all chapters with the latest medical and scientific findings, including Zika virus, red meat allergy, new viruses found in ticks, and vaccine development for malaria and dengue fever Presents a greater medical parasitology emphasis throughout Offers electronic downloads containing additional photographs of arthropod-caused diseases and lesions, as well as instructional videos with pest identification aids, basic entomology, and insect and pest ecology. Illustrated throughout with detailed color images to aid identification, The Goddard Guide to Arthropods of Medical Importance, Seventh Edition will remain an essential guide for physicians, public health officials, and pest control professionals.

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

This third edition volume expands on the previous editions with updated chapters on longitudinal studies, randomized trials, evidence-based decisions making, and a new section on changing health-related behaviors. The chapters in this book are organized into six parts: Part One focuses on framing clinical research questions and choosing a suitable design; biases that may occur in clinical research; and the ethics associated with doing conducting research on humans. Parts Two through Four discuss designs, measurements, and analysis that pertain to evaluation of risk in longitudinal studies; assessment of therapy in controlled trials; and evaluation of diagnostic tests. Part Five presents methods used in various components of evidence-based decision-making; and Part Six highlights interventions focused on changing health-related behaviors. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of various types of bias, step-by-step, readily reproducible protocols for different research designs, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Clinical Epidemiology: Methods and Protocols, Third Edition is a valuable resource for clinicians and researchers who want to expand their works to humans and use their findings in the health system.

Biopharmaceuticals (i.e., biological medicines sourced from genetically-engineered living systems) for treatment of human diseases have become a significant percentage of the pharmaceutical industry. And not just the recombinant DNA-derived proteins and monoclonal antibodies (both from the innovators and biosimilars); but now, an increasing awareness of the importance of gene therapy and genetically engineered cellular medicinal products. These biopharmaceuticals are being developed by many companies whose Chemistry, Manufacturing & Control (CMC) teams have varying degrees of familiarity or experience with the CMC strategy and regulatory compliance requirements for these challenging products. Companies clearly plan out the strategy for their clinical study plans, but frequently, the development of a strategy for CMC is an afterthought. Coupled with the complexity of the biopharmaceutical manufacturing processes and products, and this can be a recipe for disaster. The third edition of this book provides insights and practical guidance for the CMC teams to develop an acceptable cost-effective, risk-based CMC regulatory compliance strategy for all biopharmaceuticals (recombinant proteins, monoclonal antibodies, genetically engineered viruses and genetically engineered human cells) from early clinical stage development through market approval. The third edition of this book provides added coverage for the biosimilars, antibody drug conjugates (ADCs), bispecific antibodies, genetically engineered viruses, and genetically engineered cells. This third edition of the book also addresses the heightened pressure on CMC regulatory compliance timelines due to the introduction of expedited clinical pathways moving the clinical development closer to a seamless phase process (e.g., FDA Breakthrough Therapy designation, CBER Regenerative Medicine Advanced Therapy (RMAT) designation, EMA Priority Medicines (PRIME) designation). The Challenge of CMC Regulatory Compliance for Biopharmaceuticals is essential, practical information for all pharmaceutical development scientists, Manufacturing and Quality Unit staff, Regulatory Affairs personnel, and senior management involved in the manufacture of biopharmaceuticals.

The major scientific advancements in the study of nutrition and cancer in the last six years derive from the extensive use of molecular approaches to perform research in the nutritional field. Moreover, the fundamental observation of R. Doll and R. Peto (1981), which suggested that at least 35% of all cancers (with large differences among different tumors) might be prevented by dietary regimens, has been definitively confirmed by epidemiological studies. The molecular studies reported in this volume include all of the major aspects of investigation on human nutrition and malignant transformation. In the last decade a large number of compounds responsible for the biological activity of human foods has been identified and characterized. These molecules not only include important and well-known risk factors but, most promising, compounds, which might exert chemopreventive activity. Among them, antioxidants (such as vitamins, phenols, and lycopene) seem to play a critical role in reducing the risk of cancer at different anatomical sites, including colon, breast, and prostate malignancies. Other molecules, derived from fiber bacterial intestinal degradation (short fatty acids), are of interest, even if their importance has not been completely unraveled and is still the subject of debate.

Written by internationally recognized leaders in Heparanase biology, the book's eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase's multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications. Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase's multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.

Include advance knowledge and detailed developments in natural product science Discusses about the most important phytopharmaceuticals used in pharmaceutical industries Explores the analysis and classification of novel plant-based medicinal compounds Includes standardization, quality control, global trade of natural products Gives a deep understanding related to recent advances in the herbal medicines to treat various ailments Discusses about national and WHO regulations and policies related to herbal medicine Covers the complete profile of some important traditional medicinal plants especially their historical background, biology and chemistry

Cluster Randomised Trials, Second Edition discusses the design, conduct, and analysis of trials that randomise groups of individuals to different treatments. It explores the advantages of cluster randomisation, with special attention given to evaluating the effects of interventions against infectious diseases. Avoiding unnecessary mathematical detail, the book covers basic concepts underlying the use of cluster randomisation, such as direct, indirect, and total effects. In the time since the publication of the first edition, the use of cluster randomised trials (CRTs) has increased substantially, which is reflected in the updates to this edition. There are greatly expanded sections on randomisation, sample size estimation, and alternative designs, including new material on stepped wedge designs. There is a new section on handling ordinal outcome data, and an appendix with descriptions and/or generating code of the example data sets. Although the book mainly focuses on medical and public health applications, it shows that the rigorous evidence of intervention effects provided by CRTs has the potential to inform public policy in a wide range of other areas. The book encourages readers to apply the methods to their own trials, reproduce the analyses presented, and explore alternative approaches.

Skin cancer is the most frequent malignancy in humans and its incidence is still increasing. This situation calls for major efforts to manage the disease. Preventive measures must include reduced UV exposure and an enhanced common awareness of skin lesions. Advanced surgical techniques allow safe removal with excellent cosmetic results. In many cases alternative treatment modalities such as radiotherapy, cryosurgery and photodynamic therapy are applicable. The development of optimal sun screens and UV-protective clothes, new tools for early diagnosis of malignant lesions including videomicroscopy, improved evaluation of biopsy material and new treatment schemes will contribute to better patient care. New developments in therapy including pegylated interferons, cytokine-inducing molecules, monoclonal antibodies and vaccination approaches using peptides, dendritic cells, viruses or nDNA give hope for well-tolerated and efficient treatments.

Aphasia, Volume 185 covers important advances in our understanding of how language is processed in the brain and how lesions or degeneration in the left hemisphere affect language processing. This new release reviews research regarding how language recovers from brain injury, along with new interventions developed to enhance recovery, including language rehabilitation, noninvasive brain stimulation and medications. Sections cover neuroanatomy and neurophysiology of language networks, focus on mechanisms of recovery (and decline) of language, and include chapters on intervention, including recently developed behavioral therapies, brain stimulation, medications, and a review of studies of treatment for both post-stroke aphasia and primary progressive aphasia.

Atlas of Mycobacterium Tuberculosis reveals in-depth information about mycobacterium tuberculosis which has never before been reported. Using atomic force microscopy (AFM), the in-depth phenotypic interaction that occurs in different stages of the tuberculosis lifecycle is illustrated, including resting, exponential, and dormant states. Coverage also includes the macroscopic and microscopic anatomy of mycobacterium, including pigmentation, morphology of colonies, size and shape, and the phenotypic changes from susceptible to resistant, all shown with images from electronic and atomic force microscopes. This book will open a new window into the results of molecular changes at the cellular level, guiding researchers and scientists to think in new ways about the area of cell wall and the reproductive and drug resistance phenomena surrounding tuberculosis.

This work was compiled to serve as a convenient source that covers a number of techniques (and details of their use) in the rather large field of nanomedicine, with special attention paid to gene delivery. As principal investigators working in the field of nanomedicine, we sought to put together the most current and relevant topics in gene delivery, imaging and evaluation systems. We expect the work to serve very well for scientists and graduate students in the nanomedicine field.

Statistical Approaches in Oncology Clinical Development : Current Paradigm and Methodological Advancement presents an overview of statistical considerations in oncology clinical trials, both early and late phase of development. It illustrates how novel statistical methods can enrich the design and analysis of modern oncology trials. The authors include many relevant real life examples from the pharmaceutical industry and academia based on their first-hand experience. Along with relevant references, the book highlights current regulatory views. The book covers all aspects of cancer clinical trial starting from early phase development. The early part of the book covers novel phase I dose escalation design, exposure response analysis, and innovative phase II design. This includes early development strategy for cancer immunotherapy trials. The contributors also emphasized the role of biomarker and modern era of precision medicine. The second part focuses on the late stage development. This includes the application of adaptive design, safety analysis, and quality of life (QoL) data analysis. The final part discusses current regulatory perspective and challenges. Features: Covers a wide spectrum of topics related to real-life statistical challenges in oncology clinical trials. Provides a comprehensive overview of novel statistical methods to improve trial design and statistical analysis. Detailed case studies illustrate the real life applications. Satrajit Roychoudhury is a Senior Director and a member of the Statistical Research and Innovation group in Pfizer Inc. Prior to joining; he was a member of Statistical Methodology and consulting group in Novartis. He has 11 years of extensive experience in working with different phases of clinical trial. His area of research includes early phase oncology trials, survival analysis, model informed drug development, and use of Bayesian methods in clinical trials. He is industry co-chair for the ASA Biopharmaceutical Section Regulatory-Industry Workshop and has provided statistical training in major conferences including the Joint Statistical Meetings, ASA Biopharmaceutical Section Regulatory-Industry Workshop, and ICSA Applied Statistics Symposium. Soumi Lahiri has 12 years of extensive experience in working different therapeutic areas. She is the former Director of Biostatistics in Clinical Oncology, GlaxoSmithKline. She has also worked in the oncology division of Novartis Pharmaceutical Company for two years. She is an active member of the ASA Biopharmaceutical section and former chair of the membership committee.

*A focus on normal theory linking average power, expected power, predictive power, assurance, conditional Bayesian power and Bayesian power. *Extensions of the concepts to binomial, and time-to-event outcomes and non-inferiority trials *An investigation into the upper bound on average power, assurance and Bayesian power based on the prior probability of a positive treatment effect *Application of assurance to a series of trials in a development program and an introduction of the assurance of an individual trial conditional on the positive outcome of an earlier trial in the program, or to the successful outcome of an interim analysis *Prior distribution of power and sample size *Extension of the basic approach to proof-of-concept trials with dual success criteria *Investigation of the connection between conditional and predictive power at an interim analysis and power and assurance *Introduction of the idea of surety in sample sizing of clinical trials based on the width of the confidence intervals for the treatment effect, and an unconditional version.

Molecular and Cellular Basis of Metastasis: Road to Therapy, the latest in the Advances in Cancer Research series, provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics, with this volume covering the molecular and cellular basis of metastasis.

Genetics, Genomics and Fish Phenomics provides the latest information on the rapidly evolving field of genetics, presenting new medical breakthroughs that are occurring as a result of advances in our knowledge of genetics. The book continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines, critically analyzing future directions, with hhis volume focusing on genetics, genomics, and phenomics of fish.

This book brings together current advances in high-technology visualisation and the age-old but science-adapted practice of drawing for improved observation in medical education and surgical planning and practice. We begin this book with a chapter reviewing the history of confusion around visualisation, observation and theory, outlining the implications for medical imaging. The authors consider the shifting influence of various schools of philosophy, and the changing agency of technology over time. We then follow with chapters on the practical application of visualisation and observation, including emerging imaging techniques in anatomy for teaching, research and clinical practice - innovation in the mapping of orthopaedic fractures for optimal orthopaedic surgical guidance - placental morphology and morphometry as a prerequisite for future pathological investigations - visualising the dural venous sinuses using volume tracing. Two chapters explore the use and benefit of drawing in medical education and surgical planning. It is worth noting that experienced surgeons and artists employ a common set of techniques as part of their work which involves both close observation and the development of fine motor skills and sensitive tool use. An in-depth look at police identikit construction from memory by eyewitnesses to crimes, outlines how an individual's memory of a suspect's facial features are rendered visible as a composite image. This book offers anatomy educators and clinicians an overview of the history and philosophy of medical observation and imaging, as well as an overview of contemporary imaging technologies for anatomy education and clinical practice. In addition, we offer anatomy educators and clinicians a detailed overview of drawing practices for the improvement of anatomical observation and surgical planning. Forensic psychologists and law enforcement personnel will not only benefit from a chapter dedicated to the construction of facial composites, but also from chapters on drawing and observation.

This book summarizes present knowledge of different mechanisms involved in the development of positive and negative consequences of cardiac adaptation. Particular attention is paid to the still underestimated adaptive cardiac responses during development, to adaptation to the frequently occurring pressure and volume overload as well as to cardiac changes, induced by enduring exercise and chronic hypoxia. "Cardiac Adaptations" will be of great value to cardiovascular investigators, who will find this book highly useful in their cardiovascular studies for finding solutions in diverse pathological conditions; it will also appeal to students, fellows, scientists, and clinicians interested in cardiovascular abnormalities."

Advanced Statistics in Regulatory Critical Clinical Initiatives is focused on the critical clinical initiatives introduced by the 21st Century Cure Act passed by the United States Congress in December 2016. The book covers everything from the outline of the initiatives to analysis on the effect on biopharmaceutical research and development. Advanced Statistics in Regulatory Critical Clinical Initiatives provides innovative ways to resolve common challenges in statistical research of rare diseases such small sample sizes and provides guidance for combined use of data. With analysis from regulatory and scientific perspectives this book is an ideal companion for researchers in biostatistics, pharmaceutical development, and policy makers in related fields. Key Features: Provides better understanding of innovative design and analysis of each critical clinical initiatives which may be used in regulatory review/approval of drug development. Makes recommendations to evaluate submissions accurately and reliably. Proposes innovative study designs and statistical methods for oncology and/or rare disease drug development. Provides insight regarding current regulatory guidance on drug development such as gene therapy and rare diseases.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions.This book series 'Cell Biology and Translational Medicine (CBTMED)' as part of Springer Nature's long-standing and very successful Advances in Experimental Medicine and Biology book series, has the goal to accelerate advances by timely information exchange. Emerging areas of regenerative medicine and translational aspects of stem cells are covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the twelfth volume of a continuing series.

The World Health Organization supports tools and initiatives in Health Impact Assessment to dynamically improve health and well-being across different sectors. Human Impact Assessment (HuIA) is a relatively new concept. It describes an integrated process that encompasses both Health Impact Assessment and Social Impact Assessment and is used to anticipate the effects of programs, projects and decisions on human health and welfare. Sleep occupies approximately one-third of our lives, but its human impact remains largely unrecognized. The prevalence of excessive sleepiness is recognized to be increasing in industrialized societies. Without doubt, sleepiness and fatigue have high costs in terms of both lives lost and socioeconomic impact. For example, the National Highway Traffic Safety Administration estimates that up to 4% of all fatal crashes are caused by drowsy drivers and that as many as 100,000 deaths per year in the United States may be due to fatigue-related medical errors. Sleepiness and Human Impact Assessment provides a uniquely comprehensive exploration of many different facets of sleepiness in our 24-hour society from the new HuIA point of view. Among the covered issues are the physiology and pathophysiology of sleep, its relationship to daytime alertness, fatigue and drugs, the relevance of sleep-related fatigue in various occupational settings and public safety. This book will be of assistance to physicians, occupational health professionals, ergonomists, researchers and decision-makers as they strive to understand the full significance of sleepiness and to create a culture of accountability in everyday life without sleep-related risks.