This book covers the broad field of cellular, molecular, preclinical, and clinical imaging either associated with or combined with photodynamic therapy (PDT). It showcases how this approach is used clinically for cancer, infections, and diseases characterized by unwanted tissue such as atherosclerosis or blindness. Because the photosensitizers are also fluorescent, the book also addresses various imaging systems such as confocal microscopy and small animal imaging systems, and highlights how they have been used to follow and optimize treatment, and to answer important mechanistic questions. Chapters also discuss how imaging has made important contributions to clinical outcomes in skin, bladder, and brain cancers, as well as in the development of theranostic agents for detection and treatment of disease. This book provides a resource for physicians and research scientists in cell biology, microscopy, optics, molecular imaging, oncology, and drug discovery.

Judge Your Practices Against This Benchmark Manual COST Action B-24 established four working groups to research and discuss issues relevant to laboratory animal science. These included the housing of animals, environmental needs, refinement of procedures, genetically modified animals, and cost-benefit analysis. Based on the groups' findings, The COST Manual of Laboratory Animal Care and Use: Refinement, Reduction, and Research provides a consensual European view of best practices for individuals and institutions caring for and working with laboratory animals. What is COST? COST (European Cooperation in Science and Technology) is an intergovernmental initiative that promotes coordination of nationally funded science and research at a European level. This book focuses on reduction and refinement strategies and includes insightful contributions from 44 experts drawn from various EU countries. Addressing only the most commonly used mammalian species-rats, mice, and rabbits-each chapter of the book follows a similar structure: * Objectives outline the breadth of the chapter's coverage * Key Factors summarize the central issues that underpin good practice * Questions Unresolved close each chapter, identifying areas of uncertainty and prompting investigations directed at advancing knowledge and application within relevant fields The COST Manual of Laboratory Animal Care and Use: Refinement, Reduction, and Research is the reference sure to be found in the lab coats of those responsible for the care and welfare of animals and those overseeing and conducting activities related to the use of animals for scientific purposes.

Fluorescence Molecular Tomography: Principles and Applications is the first book to cover the underlying principles and practical applications of fluorescence molecular tomography (FMT) in a systematic manner. Using a tutorial approach, the text begins with an overview of the fundamentals of FMT and goes on to detail image reconstruction approaches (including linear and nonlinear reconstruction algorithms), FMT instrumentations (including time-domain, frequency-domain, and continuous-wave domain systems), and implementation of image-enhancing schemes (including both software and hardware approaches). Further chapters examine multimodal approaches combining photoacoustic tomography (PAT), computed tomography (CT), single-photon emission tomography (SPECT), and magnetic resonance imaging (MRI) and discuss bioluminescence tomography and miniaturized FMT from hand-held to endoscopic FMT. A final chapter looks at clinical applications and animal studies. This authoritative and practical guide will serve as a valuable reference for researchers, scientists, clinicians, and industry professionals. The first book dedicated to fluorescence molecular tomography (FMT); Covers underlying principles and practical applications; Written by a leading FMT research pioneer and expert.

Already popular in the analysis of medical device trials, adaptive Bayesian designs are increasingly being used in drug development for a wide variety of diseases and conditions, from Alzheimer's disease and multiple sclerosis to obesity, diabetes, hepatitis C, and HIV. Written by leading pioneers of Bayesian clinical trial designs, Bayesian Adaptive Methods for Clinical Trials explores the growing role of Bayesian thinking in the rapidly changing world of clinical trial analysis. The book first summarizes the current state of clinical trial design and analysis and introduces the main ideas and potential benefits of a Bayesian alternative. It then gives an overview of basic Bayesian methodological and computational tools needed for Bayesian clinical trials. With a focus on Bayesian designs that achieve good power and Type I error, the next chapters present Bayesian tools useful in early (Phase I) and middle (Phase II) clinical trials as well as two recent Bayesian adaptive Phase II studies: the BATTLE and ISPY-2 trials. In the following chapter on late (Phase III) studies, the authors emphasize modern adaptive methods and seamless Phase II-III trials for maximizing information usage and minimizing trial duration. They also describe a case study of a recently approved medical device to treat atrial fibrillation. The concluding chapter covers key special topics, such as the proper use of historical data, equivalence studies, and subgroup analysis. For readers involved in clinical trials research, this book significantly updates and expands their statistical toolkits. The authors provide many detailed examples drawing on real data sets. The R and WinBUGS codes used throughout are available on supporting websites. Scott Berry talks about the book on the CRC Press YouTube Channel.

The concept of frailty offers a convenient way to introduce unobserved heterogeneity and associations into models for survival data. In its simplest form, frailty is an unobserved random proportionality factor that modifies the hazard function of an individual or a group of related individuals. Frailty Models in Survival Analysis presents a comprehensive overview of the fundamental approaches in the area of frailty models. The book extensively explores how univariate frailty models can represent unobserved heterogeneity. It also emphasizes correlated frailty models as extensions of univariate and shared frailty models. The author analyzes similarities and differences between frailty and copula models; discusses problems related to frailty models, such as tests for homogeneity; and describes parametric and semiparametric models using both frequentist and Bayesian approaches. He also shows how to apply the models to real data using the statistical packages of R, SAS, and Stata. The appendix provides the technical mathematical results used throughout. Written in nontechnical terms accessible to nonspecialists, this book explains the basic ideas in frailty modeling and statistical techniques, with a focus on real-world data application and interpretation of the results. By applying several models to the same data, it allows for the comparison of their advantages and limitations under varying model assumptions. The book also employs simulations to analyze the finite sample size performance of the models.

This book presents the functions and mechanisms of macropinocytosis, an actin-driven endocytic uptake process. Key points, including the evolutionary origins of macropinocytosis and major signaling pathways that regulate this uptake mechanism, are highlighted. A wide-array of functions of macropinocytosis are described, including cellular metabolism, cell death, cell migration and antigen presentation. Macropinocytosis has recently been recognized as a critical pathway in disease pathology and treatment. Therefore, a broad overview of macropinocytosis will benefit clinicians, as well as translational and basic research scientists. Moreover, as one of the main clathrin-independent endocytic routes, compiling all the critical information about macropinocytosis in one collection, this book will also be helpful to educators and their students.

The practice of medicine is both learned and advanced through the compilation and study of cases -- vignettes that record the presentation, diagnosis, and treatment of individual patients and diseases. This is especially true of psychosomatic medicine (PSM), which depends on the "compelling case" to distill clinical knowledge and communicate it to students, residents, and clinicians. An invaluable contribution to the field, the Casebook of Psychosomatic Medicine describes the psychiatric symptoms and/or illnesses managed by the PSM psychiatrist in collaboration with other medical colleagues. The book presents a broad range of cases illustrating the medical, psychosocial, and intertwined situations psychiatrists are likely to encounter in an academic medical center setting.

No other single volume offers a broader range of engaging, detailed, and nuanced PSM cases, or grounds them so firmly in a psychiatric, psychosocial, and spiritual context. Here are just a few of this patient-centered book's most impressive and useful features: - The relevant science underlying each case is addressed in discussion sections, allowing the book to be read as a stand-alone volume. Alternatively, the cases can be read as instructive and insightful illustrations by the reader who has already absorbed the fundamentals of PSM from standard textbooks in the field.- This user-friendly book is organized by the organ system or disease type of the presenting illness or symptom.- Content rare in volumes of this kind includes detailed coverage of the diagnosis and management of cognitive disorders; the management of drug toxicity states; determinations of decisional capacity for medical decision making; and "stress and adaptation," an issue the PSM psychiatrist encounters daily.- The authors strongly believe that one of the most crucial roles for the psychiatrist is in the medical center, and the book reflects that orientation. - The book addresses the importance of understanding the impact of patients' systemic illnesses on their psychiatric symptoms, and modifying interventions and care accordingly. These abilities are critical to sound PSM practice.

Although PSM has a long and noble history, it is the newest of the psychiatric subspecialties, and as the literature expands, more and more clinicians will incorporate PSM treatment modalities into their practice. The Casebook of Psychosomatic Medicine is an essential contribution to that body of knowledge and establishes a new standard with which to face the future of this exciting field.

Design Principles and Analysis Techniques for HRQoL Clinical Trials
SAS, R, and SPSS examples realistically show how to implement methods

Focusing on longitudinal studies, Design and Analysis of Quality of Life Studies in Clinical Trials, Second Edition addresses design and analysis aspects in enough detail so that readers can apply statistical methods, such as mixed effect models, to their own studies. The author illustrates the implementation of the methods using the statistical software packages SAS, SPSS, and R.

New to the Second Edition

• Data sets available for download online, allowing readers to replicate the analyses presented in the text
• New chapter on testing models that involve moderation and mediation
• Revised discussions of multiple comparisons procedures that focus on the integration of health-related quality of life (HRQoL) outcomes with other study outcomes using gatekeeper strategies
• Recent methodological developments for the analysis of trials with missing data
• New chapter on quality adjusted life-years (QALYs) and QTWiST specific to clinical trials
• Additional examples of the implementation of basic models and other selected applications in R and SPSS

This edition continues to provide practical information for researchers directly involved in the design and analysis of HRQoL studies as well as for those who evaluate the design and interpret the results of HRQoL research. By following the examples in the book, readers will be able to apply the steps to their own trials.

An important factor that affects the duration, complexity and cost of a clinical trial is the endpoint used to study the treatment's efficacy. When a true endpoint is difficult to use because of such factors as long follow-up times or prohibitive cost, it is sometimes possible to use a surrogate endpoint that can be measured in a more convenient or cost-effective way. This book focuses on the use of surrogate endpoint evaluation methods in practice, using SAS and R.

Design and Analysis of Clinical Trials for Predictive Medicine provides statistical guidance on conducting clinical trials for predictive medicine. It covers statistical topics relevant to the main clinical research phases for developing molecular diagnostics and therapeutics-from identifying molecular biomarkers using DNA microarrays to confirming their clinical utility in randomized clinical trials. The foundation of modern clinical trials was laid many years before modern developments in biotechnology and genomics. Drug development in many diseases is now shifting to molecularly targeted treatment. Confronted with such a major break in the evolution toward personalized or predictive medicine, the methodologies for design and analysis of clinical trials is now evolving. This book is one of the first attempts to contribute to this evolution by laying a foundation for the use of appropriate statistical designs and methods in future clinical trials for predictive medicine. It is a useful resource for clinical biostatisticians, researchers focusing on predictive medicine, clinical investigators, translational scientists, and graduate biostatistics students.

The growing interest in using combination drugs to treat various complex diseases has spawned the development of many novel statistical methodologies. The theoretical development, coupled with advances in statistical computing, makes it possible to apply these emerging statistical methods in in vitro and in vivo drug combination assessments. However, despite these advances, no book has served as a single source of information for statistical methods in drug combination research, nor has there been any guidance for experimental strategies. Statistical Methods in Drug Combination Studies fills that gap, covering all aspects of drug combination research, from designing in vitro drug combination studies to analyzing clinical trial data. Featuring contributions from researchers in industry, academia, and regulatory agencies, this comprehensive reference: Describes statistical models used to characterize dose-response patterns of monotherapies and evaluate the combination drug synergy Offers guidance for estimating interaction indices and constructing their associated confidence intervals to assess drug interaction Introduces a practical and innovative Bayesian approach to Phase I cancer trials, including actual trial examples to illustrate use Examines strategies in the fixed-dose combination therapy clinical development via case studies stemming from regulatory reviews Evaluates computational tools and software packages used to apply novel statistical methods in combination drug development Statistical Methods in Drug Combination Studies provides researchers with a solid understanding of the available statistical methods and computational tools and how to apply them in drug combination studies. The book is equally useful for statisticians to become better equipped to deal with drug combination study design and analysis in their practice.

Researching, Reflecting and Writing about Work provides a guide to the research skills and critical thinking required to complete a research project for professional learning courses in counselling and psychotherapy.

Written at a level easily accessible to those enrolled on a work-based qualification as well as those considering postgraduate research at master's level, this book includes:

• how we reflect on our work
• discussion on preparation and structuring of a case study
• how to present work in supervision with advice on process recording
• essay plan structures and appropriate methodologies for research
• ethical considerations and critical linking
• dilemmas and tensions involved in research at work .

Key learning points and reflective exercises are included throughout and theory is supported by contributions detailing specific learning experiences from a variety of work settings, including the public sector, an organisation, in the community, and as an independent counsellor in a voluntary agency. There is also a section on how to prepare your research for consideration for publication and how to present your findings to colleagues.

Researching, Reflecting and Writing about Work will be of interest to all those on counselling courses, or training as psychotherapists, as well as people involved in professional learning linked to the helping professions, including those interested in work-based research linked to therapy in any setting.

Stem cells are central to the development and homeostasis of metazoan tissues and play roles at multiple times within a diversity of organs during the lifetime of an animal. A key goal of regenerative medicine is the in vivo repair of organs damaged by disease or injury. In order to facilitate this goal we need to understand how stem cells are generated, what factors maintain them in their respective tissues and how their differentiation is regulated. In this volume, leading researchers discuss the nature of stem cells and pluripotency and how this state can be experimentally induced. Stem cell maintenance, proliferation and differentiation is under tight regulation as excess stem cell proliferation could facilitate tumour formation and conversely loss of stem cells or failure of differentiation could disrupt tissue homeostasis or repair. Hence, stem cells are regulated by multiple layers of molecular control and this volume discusses transcriptional, translational, epigenetic, cell signalling and microRNA modalities that affect stem cell behaviour. Many of the underlying key principles of stem cell biology were discovered by genetic analysis of invertebrate systems and chapters in this volume describe regulation of the germline in C. elegans and in the digestive system, central nervous system and germline of Drosophila. The molecular processes that regulate regenerative organ systems from all three of the vertebrate germ layers are described with emphasis on the male germline, nervous system, epidermis, intestine, haematopoietic system and derivatives of the mesoderm. Several chapters also focus on molecular families that have been implicated in controlling a range of stem cell types including the JAK-STAT, Wnt and Notch signalling pathways; Myc, Myb and nuclear receptor transcriptional regulators; the Musashi family of RNA-binding proteins; microRNAs and epigenetic regulators. This volume will provide access to the current state of re

Statistical Methods for Survival Trial Design: With Applications to Cancer Clinical Trials Using R provides a thorough presentation of the principles of designing and monitoring cancer clinical trials in which time-to-event is the primary endpoint. Traditional cancer trial designs with time-to-event endpoints are often limited to the exponential model or proportional hazards model. In practice, however, those model assumptions may not be satisfied for long-term survival trials. This book is the first to cover comprehensively the many newly developed methodologies for survival trial design, including trial design under the Weibull survival models; extensions of the sample size calculations under the proportional hazard models; and trial design under mixture cure models, complex survival models, Cox regression models, and competing-risk models. A general sequential procedure based on the sequential conditional probability ratio test is also implemented for survival trial monitoring. All methodologies are presented with sufficient detail for interested researchers or graduate students.

Repeated Measures Design with Generalized Linear Mixed Models for Randomized Controlled Trials is the first book focused on the application of generalized linear mixed models and its related models in the statistical design and analysis of repeated measures from randomized controlled trials. The author introduces a new repeated measures design called S:T design combined with mixed models as a practical and useful framework of parallel group RCT design because of easy handling of missing data and sample size reduction. The book emphasizes practical, rather than theoretical, aspects of statistical analyses and the interpretation of results. It includes chapters in which the author describes some old-fashioned analysis designs that have been in the literature and compares the results with those obtained from the corresponding mixed models. The book will be of interest to biostatisticians, researchers, and graduate students in the medical and health sciences who are involved in clinical trials. Author Website:Data sets and programs used in the book are available at http://www.medstat.jp/downloadrepeatedcrc.html

Discover the Latest Statistical Approaches for Modeling Exposure-Response Relationships Written by an applied statistician with extensive practical experience in drug development, Exposure-Response Modeling: Methods and Practical Implementation explores a wide range of topics in exposure-response modeling, from traditional pharmacokinetic-pharmacodynamic (PKPD) modeling to other areas in drug development and beyond. It incorporates numerous examples and software programs for implementing novel methods. The book describes using measurement error models to treat sequential modeling, fitting models with exposure and response driven by complex dynamics, and survival analysis with dynamic exposure history. It also covers Bayesian analysis and model-based Bayesian decision analysis, causal inference to eliminate confounding biases, and exposure-response modeling with response-dependent dose/treatment adjustments (dynamic treatment regimes) for personalized medicine and treatment adaptation. Many examples illustrate the use of exposure-response modeling in experimental toxicology, clinical pharmacology, epidemiology, and drug safety. Some examples demonstrate how to solve practical problems while others help with understanding concepts and evaluating the performance of new methods. The provided SAS and R codes enable readers to test the approaches in their own scenarios. Although application oriented, this book also gives a systematic treatment of concepts and methodology. Applied statisticians and modelers can find details on how to implement new approaches. Researchers can find topics for or applications of their work. In addition, students can see how complicated methodology and models are applied to practical situations.

In a global clinical development strategy, multiregional clinical trials (MRCTs) are vital in the development of innovative medicines. Multiregional Clinical Trials for Simultaneous Global New Drug Development presents a comprehensive overview on the current status of conducting MRCTs in clinical development. International experts from academia, industry, and health organizations address various aspects of the important problems in global clinical development and MRCTs. The book first provides a high-level introduction to the context, motivation, opportunities, and challenges in simultaneous global clinical development using MRCTs. It then focuses on the design, monitoring, and analysis/interpretation of MRCTs. The book concludes with an examination of the latest research topics from MRCT perspectives, such as special considerations by local health authorities, health economic evaluations, benefit-risk assessment, and medical devices. Explaining how to design, conduct, and interpret MRCTs, this book will help biostatisticians working in the late-stage clinical development of medical products. It will also be useful for statisticians and clinicians in the biopharmaceutical industry, regulatory agencies, and medical research institutes.

Develop Effective Immunogenicity Risk Mitigation Strategies Immunogenicity assessment is a prerequisite for the successful development of biopharmaceuticals, including safety and efficacy evaluation. Using advanced statistical methods in the study design and analysis stages is therefore essential to immunogenicity risk assessment and mitigation strategies. Statistical Methods for Immunogenicity Assessment provides a single source of information on statistical concepts, principles, methods, and strategies for detection, quantification, assessment, and control of immunogenicity. The book first gives an overview of the impact of immunogenicity on biopharmaceutical development, regulatory requirements, and statistical methods and strategies used for immunogenicity detection, quantification, and risk assessment and mitigation. It then covers anti-drug antibody (ADA) assay development, optimization, validation, and transfer as well as the analysis of cut point, a key assay performance parameter in ADA assay development and validation. The authors illustrate how to apply statistical modeling approaches to establish associations between ADA and clinical outcomes, predict immunogenicity risk, and develop risk mitigation strategies. They also present various strategies for immunogenicity risk control. The book concludes with an explanation of the computer codes and algorithms of the statistical methods. A critical issue in the development of biologics, immunogenicity can cause early termination or limited use of the products if not managed well. This book shows how to use robust statistical methods for detecting, quantifying, assessing, and mitigating immunogenicity risk. It is an invaluable resource for anyone involved in immunogenicity risk assessment and control in both non-clinical and clinical biopharmaceutical development.

This book focuses on analytical similarity assessment in biosimilar product development following the FDA's recommended stepwise approach for obtaining totality-of-the-evidence for approval of biosimilar products. It covers concepts such as the tiered approach for assessment of similarity of critical quality attributes in the manufacturing process of biosimilar products, models/methods like the statistical model for classification of critical quality attributes, equivalence tests for critical quality attributes in Tier 1 and the corresponding sample size requirements, current issues, and recent developments in analytical similarity assessment.

This new volume, Promising Drug Molecules of Natural Origin, explores potential beneficial drug substances derived from nature. It presents the general principles, characteristics, evaluation techniques, and applications involved in drug molecules from natural sources, such as plants and marine life. With chapters from renowned experts from around the world, the chapters in this volume address the challenges of standardization of herbal medicines, methods of characterization of natural medicines and phyto-constituents, and quality control methods for herbal medicines. Several chapters in the book focus on the evolution of phyto-constituents in cancer therapeutics, while others deal with applications for other diseases, such as diabetes and neuroinflammatory disorders. The volume also specifically reviews heterocyclic drugs from plants. This volume will be a valuable resource for faculty and advanced students in pharmaceutics as well as researchers, scientists, and industry professionals in medicine and drug development.

Now in its second edition, this handbook collects authoritative contributions on modern methods and tools in statistical bioinformatics with a focus on the interface between computational statistics and cutting-edge developments in computational biology. The three parts of the book cover statistical methods for single-cell analysis, network analysis, and systems biology, with contributions by leading experts addressing key topics in probabilistic and statistical modeling and the analysis of massive data sets generated by modern biotechnology. This handbook will serve as a useful reference source for students, researchers and practitioners in statistics, computer science and biological and biomedical research, who are interested in the latest developments in computational statistics as applied to computational biology.

Reviews in Plasmonics 2010, the first volume of the new book serial from Springer, serves as a comprehensive collection of current trends and emerging hot topics in the field of Plasmonics and closely related disciplines. It summarizes the year's progress in surface plasmon phenomena and its applications, with authoritative analytical reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of Plasmonics. Reviews in Plasmonics offers an essential reference material for any lab working in the Plasmonics field and related areas. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of Plasmonics will find it an invaluable resource. Key features: Accessible utility in a single volume reference. Chapters authored by known leading figures in the Plasmonics field. New volume publishes annually. Comprehensive coverage of the year's hottest and emerging topics. Reviews in Plasmonics 2011 topics include: Metal Nanoparticles for Molecular Plasmonics. Surface Plasmon Resonance based Fiber Optic Sensors. Elastic Light Scattering of Biopolymer/Gold Nanoparticles Fractal Aggregates. Influence of electron quantum confinement on the electronic response of metal/metal interfaces. Melting Transitions of DNA-Capped Gold Nanoparticle Assemblies. Nanomaterial Based Long Range Optical Ruler for Monitoring Biomolecular Activities. Plasmonic Gold and Silver Films: Selective Enhancement of Chromophore Raman Scattering or Plasmon-Assisted Fluorescence.

Culture and Meaning in Health Services Research is a practical guide to applying interpretive qualitative methods to pressing healthcare delivery problems. A leading medical anthropologist who has spent many years working in applied healthcare settings, Sobo combines sophisticated theoretical insights and methodological rigor with authentic, real-world examples and applications. In addition to clearly explaining the nuanced practice of ethnography and guiding the reader through specific methods that can be used in focus groups or interviewing to yield useful findings, Sobo considers the social relationships and power dynamics that influence field entry, data ownership, research deliverables, and authorship decisions. Crafted to communicate the importance of culture and meaning across the many disciplines engaged in health services research, this book is ideal for courses in such fields as public health and health administration, nursing, anthropology, health psychology, and sociology.

This book brings together a collection of empirical case studies featuring a wide spectrum of medical innovation. While there is no unique pathway to successful medical innovation, recurring and distinctive features can be observed across different areas of clinical practice. This book examines why medical practice develops so unevenly across and within areas of disease, and how this relates to the underlying conditions of innovation across areas of practice. The contributions contained in this volume adopt a dynamic perspective on medical innovation based on the notion that scientific understanding, technology and clinical practice co-evolve along the co-ordinated search for solutions to medical problems. The chapters follow an historical approach to emphasise that the advancement of medical know-how is a contested, nuanced process, and that it involves a variety of knowledge bases whose evolutionary paths are rooted in the contexts in which they emerge. This book will be of interest to researchers and practitioners concerned with medical innovation, management studies and the economics of innovation. Chapter 5 of this book is freely available as a downloadable Open Access PDF under a Creative Commons Attribution-Non Commercial-No Derivatives 3.0 license. https://s3-us-west-2.amazonaws.com/tandfbis/rt-files/docs/Open+Access+Chapters/9781138860346_oachapter5.pdf

This volume is dedicated to multidisciplinary research at the interface between basic biomedicine and clinical practice. This book guides best practice in the diagnosis and therapy while dealing with difficult-to-treat disorders of yet unclear etiology. Chapters address such disorders as granulomatosis with polyangiitis causing autoimmune-related multiorgan inflammation of blood vessels, increasingly widespread allergy to peanuts, occupational exposure to zinc oxide, and immunogenic responses to pneumococcal and influenza vaccination underlying their preventive effectiveness. Other hot issues deal with the proper use of fluid therapy in the perioperative period and a cognitive decline in lung transplant patients. A new physiotherapeutic approach of treating key myofascial trigger points in low-back pain appears highly beneficial in reducing patients' disability, advancing physiotherapy of this overwhelming condition. Finally, other chapters consider ways to streamline medical management to increase the number of physicians and their availability for patients, a particularly sensitive issue in the current COVID-19 pandemic. The dissemination of clinical knowledge about high-risk and hardly controllable conditions is an inalienable part of progress in medical practice. The book is a resource for clinical specialists, general practitioners, and allied healthcare professionals.