Growth in the pharmaceutical market has slowed down - almost to a standstill. One reason is that governments and other payers are cutting costs in a faltering world economy. But a more fundamental problem is the failure of major companies to discover, develop and market new drugs. Major drugs losing patent protection or being withdrawn from the market are simply not being replaced by new therapies - the pharmaceutical market model is no longer functioning effectively and most pharmaceutical companies are failing to produce the innovation needed for success. This multi-authored new book looks at a vital strategy which can bring innovation to a market in need of new ideas and new products: Systems Biology (SB). Modeling is a significant task of systems biology. SB aims to develop and use efficient algorithms, data structures, visualization and communication tools to orchestrate the integration of large quantities of biological data with the goal of computer modeling. It involves the use of computer simulations of biological systems, such as the networks of metabolites comprise signal transduction pathways and gene regulatory networks to both analyze and visualize the complex connections of these cellular processes. SB involves a series of operational protocols used for performing research, namely a cycle composed of theoretical, analytic or computational modeling to propose specific testable hypotheses about a biological system, experimental validation, and then using the newly acquired quantitative description of cells or cell processes to refine the computational model or theory.

In this monograph, the author -Head researcher at the Institute of Cell Biophysics of Russian Academy of Sciences- discusses the results of his own long-term studies of mitochondria as well as alternative points of view and experiments of other important researchers in the field. The monograph contains the main aspects of mitochondrial research by a number of physical methods: fluorescence spectroscopy, UV-vis spectrophotometry, IR spectroscopy, light-scattering, optical microscopy, fluorescence microscopy, colorimetry, photobleaching, polarography, among others. The monograph is very useful for researchers and graduate students specializing in mitochondrial biophysics, biochemistry, molecular biology and cytology. The book was published in Russian in 2019 by Photon Publishers (Pushchino, Moscow region).

Every month, groups of people from all over the United Kingdom decide what kind of research should be carried out on patients within the NHS. These groups - Research Ethics Committees (RECs) - made up of doctors, nurses, researchers, and members of the general public - help shape the future of medicine, and play a crucial role in the regulation of a wide range of research from social science to epidemiology, vaccine and drugs trials to surgery. Based on extensive observations, interviews, and archival research, this book provides an in-depth insight into RECs, one of the most crucial forms of regulation around medical research. In providing one of the first empirical examinations of this kind of regulation, this book challenges the impersonal, de-socialised, and mechanical models of REC decision-making. -- .

Natural products have a long history of use as folk medicines in several systems of traditional medicine. Extensive evidence from modern pharmacological studies has confirmed traditional applications, and unveiled the vast potential of naturally occurring compounds, particularly plant-derived phytochemicals, in the management of chronic human diseases. The past decade has witnessed a surge of findings from randomized controlled trials testifying the safety and efficacy of natural products as adjuncts or alternatives to standard-of-care medications for several illnesses. Biomolecular studies have unveiled hundreds of cellular and molecular targets for phytochemicals including key transcription factors, receptors, enzymes, hormones, neurotransmitters, cytokines, lipids, and non-coding RNAs. Extensive research on the preventative and therapeutic effects of natural products necessitates regular updating of the literature as to the developing potential roles of these compounds in different human diseases. This new book provides an overview of the current pharmacological and clinical features of natural products, and the role of phytopharmaceutical compounds in health and diseases. Chapters cover a wide scope, from cancers, to chronic and age-related disorders, and are written by leading international subject experts. Collectively, chapters will provide useful insights on the regulatory effects of phytochemicals and nutraceuticals on pathogenic molecular signatures associated with pathologies, disease biomarkers, and aging-related pathways.

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes."

Much has been written about the basic incompatibility of the dominant quantitative research model in psychotherapy and the qualitative preferences of the practitioner community providing psychotherapy. Researchers and clinicians are at odds over the most valuable type of knowledge needed: that emerging from quantitative, experimental research versus that from qualitative, case-based practice, respectively. Recently, a number of emerging research methods have attempted to bridge and integrate these two approaches. Case Studies within Psychotherapy Trials is one such effort and significantly furthers the synergy between them. The volume provides a comprehensive illustration of the "cases-within-trials" (CWT) model of research. Quantitative findings from four randomized clinical trials (RCT) are synthesized with qualitative and quantitative findings from systematic case studies of successful and unsuccessful clients representatively drawn from each RCT. The book opens with the history of dialectic and political controversy in psychotherapy research and recent initiatives to bridge the differing perspectives. The RCT and case study projects follow, each commented on by outside experts. In the final chapter the editors compare and contrast the separate projects and draw insightful, impactful conclusions. By bringing together quantitative, natural scientific perspectives on research and qualitative, interpretative understandings and strategies, the chapter authors demonstrate how practitioners can be meaningfully included in future psychotherapy research. This book will be of great interest to psychotherapy researchers and practitioners and those interested in research methods in the behavioral sciences more generally.

Provides a comprehensive review of challenges and opportunities as related to the applications of big data, AI, and machine learning in the entire spectrum of drug R&D Discusses regulatory developments in leveraging big data and advanced analytics in drug review and approval Offers a balanced approach to data science organization build Presents real-world examples of AI-powered solutions to a host of issues in the lifecycle of drug development Affords sufficient context for each problem and provides detailed description of solutions suitable for practitioners with limited data science expertise

This book is a compendium of articles providing insights into a range of contemporary ideas concerning the core yet unsettled clinical issues. Important aspects of pulmonary disorders are tackled such as occupational respiratory health hazards, asthma, or the role of vitamin D in obstructive airway diseases. Genotyping offers a clear promise in the diagnostics of chronic pulmonary lesions of autoimmune background. Cardiac and respiratory-driven pulsation of cerebrospinal fluid content offers novel arguments in the pathophysiologic savvy of a range of brain dysfunctional conditions, including respiratory-related hypoxic pathologies. Some other articles tackle the heady topics of rehabilitation medicine, offering an insight into research-underpinned diagnostics and practical management solutions in a range of musculoskeletal disorders and injuries that affect the human body's movement, particularly those controlled by the autonomic nervous system. The book is addressed to clinicians, researchers, physiotherapists, and medical professionals engaged in patient care.

Essentials from the series "Applied Scanning Probe Methods" are put together in the area of bio and biorelated systems. The contributions spread over all 13 volumes are now combined in this one volume. Thus, the reader will easily find a comprehensive overview of SPM applications for biosystems.

For scientists and professionals in academic and industry dealing with surface analytics of plant science, living cells, nanomedicine, cosmetics and biomimetics.

Posttraumatic Epilepsy: Basic and Clinical Aspects provides a synthesized resource on the recent basic and clinical science developments in the field of posttraumatic epilepsy. This book provides a clear understanding of the history of studies and epidemiology of posttraumatic epilepsy after head injury. The book also considers the neuropathology of posttraumatic epilepsy and clinical trials of antiepileptogenic agents evaluated after traumatic brain injury. The book covers the basic science of animal models of traumatic brain injury and the necessary and sufficient changes that must occur to generate epilepsy after head trauma. The authors explore potential mechanisms and novel therapeutic approaches to prevent posttraumatic epilepsy. The book is written for basic and clinical researchers in neuroscience as well as for clinicians treating patients with epilepsy.

This book embraces a comprehensive range of research across several disciplines, providing insights and fresh perspectives on clinical topics, emphasizing the integrative medical approach. The book also addresses an increasing role of artificial intelligence in the development of clinical methodologies, research, and patient-oriented care. The authors share expertise and experience in rehabilitation medicine whose healing-effects particularly depend on the interaction between the therapist and patient. Chapters present novel approaches in manual rehabilitative therapy of common painful and disabling neuromuscular ailments, exemplified but not limited to low back pain and migraine. The myofascial trigger point release therapy includes specific manipulations to muscles and connective tissue which reduce pain. Other chapters address the issues of providing long-range medical care to older adults burdened with chronic diseases, notably hypoxia-related pathologies and their sequalae, pointing to the advantages of care provided by a single primary care physician. Changing paradigm of care is essential in chronic atherosclerosis-based diseases like cardiovascular disorders or diabetes. Chapters provide results of international cohort studies on predictive factors for the long-range progress of such ailments based on anthropometric and lifestyle indicators. The book aims to meet the increasing interest and importance to patients of integrative health therapies. Medical rehabilitation and lifestyle changes increasingly gain scientific support in difficult-to-treat chronic conditions and should be integrated in a controlled manner into conventional medicine. The book is addressed to physiotherapists, medical scientists and clinicians, and allied healthcare professionals.

This multi-chapter book focuses on one of the hottest topics in ageing research - the role of hormones in health and longevity, offering a comprehensive and up-to-date overview of their mechanistic roles in health, ageing and longevity. Hormones are an excellent system of communication between cells and tissues within an organism, and they coordinate a wide range of processes in biological systems, including neuroendocrine and immunological controls. The book offers insights into the latest significant advances in our understanding of the mechanisms of hormonal signaling that control a variety of processes involved in development and ageing. It is divided into four parts: Part I includes a review of the hundred-year history of hormones by the illustrious hormone biochemist Dr. J.R. Tata. Part II presents various chapters on the hormones involved in growth, stress and metabolism, while Part III addresses the hormones controlling cognition and rhythms in ageing processes. Lastly, Part IV discusses the hormones affecting reproduction, immunity and life span. It also explores the use of hormones as pharmaceuticals to maintain health in the elderly. It is a valuable resource for those working in the area of hormone signaling in general and in the field of ageing research in particular.

Asthma is a chronic relapsing airways disease that represents a major public health problem worldwide. Intermittent exacerbations are provoked by airway mucosal exposure to pro-inflammatory stimuli, with RNA viral infections or inhaled allergens representing the two most common precipitants. In this setting, inducible signaling pathways the airway mucosa play a central role in the initiation of airway inflammation through production of antimicrobial peptides (defensins), cytokines, chemokines and arachidonic acid metabolites that coordinate the complex processes of vascular permeability, cellular recruitment, mucous hyper-secretion, bronchial constriction and tissue remodeling. These signals also are responsible for leukocytic infiltration into the submucosa, T helper-lymphocyte skewing, and allergic sensitization. Currently, it is well appreciated that asthma is a heterogeneous in terms of onset, exacerbants, severity, and treatment response. Current asthma classification methods are largely descriptive and focus on a single aspect or dimension of the disease. An active area of investigation on how to collect, use and visualize multidimensional profiling in asthma. This book will overview multidimensional profiling strategies and visualization approaches for phenotyping asthma. As an outcome, this work will facilitate the understanding of disease etiology, prognosis and/or therapeutic intervention. "

This volume reviews disparities in cancer genetics, etiology, treatment and survivorship that are associated with differences in energy balance and how those differences and disparities may be affected by geography, socioeconomic status, ethnicity, biology, behavior and others. State-of-the-art strategies are outlined to alter these problems at the individual, community and policy levels. The book provides a comprehensive assessment of the multiple contributions of disparities in energy balance and how they affect cancer. this volume should constitute a valuable resource to disparity focused investigators at all levels and serves an important guide to professionals that deal with these issues, especially those who determine and implement policy."

This book provides a concise yet comprehensive review of the morphological, biochemical, electrical, mechanical, and metabolic properties of vascular smooth muscle, the regulation of vascular activities and the intracellular signaling involved. It particularly focuses on newly identified vasoactive agents, enzymes and transduction mechanisms. It also discusses the latest findings in the regulation of cerebral, coronary and pulmonary circulation as well as vascular activity under hypoxia and ageing. The second edition intends to update the contents of the first edition with the latest achievements in the regulation of vascular activities from biochemical, structural, genetic, physiological, and pharmacological aspects. In addition, two new chapters related to microRNA and extracellular vesicles have been added to reflect their newly discovered important roles in vascular activities. The contraction and dilatation activities of vasculature are of fundamental importance for maintaining circulation homeostasis and adapting to physiological changes. Over the last four decades, there have been significant advances in our understanding of the biochemical, structural, genetic, physiological, and pharmacological aspects of vascular activity regulation, and these insights into the responsiveness of blood vessels under normal and pathophysiological conditions help to provide valuable weapons in the fight vascular diseases. The book is of interest to researchers and graduate students, both in basic research and in clinic settings, in the field of vascular biology.

Survival analysis generally deals with analysis of data arising from clinical trials. Censoring, truncation, and missing data create analytical challenges and the statistical methods and inference require novel and different approaches for analysis. Statistical properties, essentially asymptotic ones, of the estimators and tests are aptly handled in the counting process framework which is drawn from the larger arm of stochastic calculus. With explosion of data generation during the past two decades, survival data has also enlarged assuming a gigantic size. Most statistical methods developed before the millennium were based on a linear approach even in the face of complex nature of survival data. Nonparametric nonlinear methods are best envisaged in the Machine Learning school. This book attempts to cover all these aspects in a concise way. Survival Analysis offers an integrated blend of statistical methods and machine learning useful in analysis of survival data. The purpose of the offering is to give an exposure to the machine learning trends for lifetime data analysis. Features: Classical survival analysis techniques for estimating statistical functional and hypotheses testing Regression methods covering the popular Cox relative risk regression model, Aalen's additive hazards model, etc. Information criteria to facilitate model selection including Akaike, Bayes, and Focused Penalized methods Survival trees and ensemble techniques of bagging, boosting, and random survival forests A brief exposure of neural networks for survival data R program illustration throughout the book

Precision Medicine in Neurodegenerative Disorders, Part One, Volume 192 deals with the "Why" in the approach to slow the progression of those suffering from diseases of accelerated brain aging. Matching a biology-correcting therapy with those biologically suitable to benefit from such therapy represents the vision and mission of precision medicine, the highest level of personalized medicine. This first Handbook of Clinical Neurology volume is intended to provide a scholarly background on the framework, basic science, and conceptual pitfalls related to disease-modifying efforts in Parkinson, Alzheimer, and other neurodegenerative disorders. Among the topics covered are the different models of precision medicine, the lumping-versus-splitting tension in biomarker development and therapeutics, and the rationale for replacing the convergence of the prevailing autopsy-based nosology of neurodegenerative diseases with the divergence of a systems biology approach to human diseases. Specific chapters are dedicated to the promise of genetic subtypes and the lessons in disease modification offered by the fields of oncology and cystic fibrosis that can be adapted to the field of neurodegeneration.

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.

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

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.

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.

Concise, contemporary, and accessible to students with little-to-no prior knowledge of nursing theory, Theoretical Basis for Nursing, 6th Edition, clarifies the application of theory and helps students become more confident, well-rounded nurses. With balanced coverage of grand, middle range, and shared theories, this acclaimed, AJN Award-winning text is extensively researched and easy to read, providing an engaging, approachable guide to developing, analyzing, and evaluating theory in students' nursing careers. Updated content reflects the latest perspectives on clinical judgment, evidence-based practice, and situation-specific theories, accompanied by engaging resources that give students the confidence to apply concepts to their own practice.