Millions of children suffer from diseases and illnesses that do not have adequate treatment, and many other children are harmed by medicines intended to help them. In order to protect and help these children, society must conduct pediatric research to identify safer and more effective medical treatments. This research requires exposing some children to risks for the benefit of others. Yet, critics and courts have argued that it is unethical to expose children to research risks for the benefit of others, and this practice seems to violate our obligation to protect children from harm and exploitation. In this way, clinical research with children presents us with what appears to be an irresolvable dilemma: either we can protect pediatric subjects from exploitation, or we can protect pediatric patients from dangerous medicines, but not both.
The Ethics of Pediatric Research is the first work to systematically evaluate this dilemma, and David Wendler offers an original justification for pediatric research based on an in-depth analysis of when it is in our interests to help others. It will be of interest primarily to scholars in pediatric ethics and clinical research ethics.

This book summarizes the latest research findings in the neurocircuitry of innate behaviors, covering major topics such as innate fear, aggression, feeding, reward, social interaction, parental care, spatial navigation, and sleep-wake regulation. For decades, humans have been fascinated by wild animals' instincts, like the annual two-thousand-mile migration of the monarch butterfly in North American, and the "imprint" behavior of newborn birds. Since these instincts are always displayed in stereotypical patterns in most individuals of a given species, the neural circuits processing such behaviors must be genetically hard-wired in the brain. Recently, with the development of modern techniques, including optogenetics, retrograde and anterograde virus tracing, and in vivo calcium imaging, researchers have been able to determine and dissect the specific neural circuits for many innate behaviors by selectively manipulating well-defined cell types in the brain. This book discusses recent advances in the investigation of the neural-circuit mechanisms underlying innate behaviors.

This book covers classic epidemiological designs that use a reference/control group, including case-control, case-cohort, nested case-control and variations of these designs, such as stratified and two-stage designs. It presents a unified view of these sampling designs as representations of an underlying cohort or target population of interest. This enables various extended designs to be introduced and analysed with a similar approach: extreme sampling on the outcome (extreme case-control design) or on the exposure (exposure-enriched, exposure-density, countermatched), designs that re-use prior controls and augmentation sampling designs. Further extensions exploit aggregate data for efficient cluster sampling, accommodate time-varying exposures and combine matched and unmatched controls. Self-controlled designs, including case-crossover, self-controlled case series and exposure-crossover, are also presented. The test-negative design for vaccine studies and the use of negative controls for bias assessment are introduced and discussed. This book is intended for graduate students in biostatistics, epidemiology and related disciplines, or for health researchers and data analysts interested in extending their knowledge of study design and data analysis skills. This book Bridges the gap between epidemiology and the more mathematically oriented biostatistics books. Assembles the wealth of epidemiological knowledge about observational study designs that is scattered over several decades of scientific publications. Illustrates the performance of methods in real research applications. Provides guidelines for implementation in standard software packages (Stata, R). Includes numerous exercises, covering simple mathematical proofs, consideration of proposed or published designs, and practical data analysis.

This book aims to present the age-related alterations in redox signaling networks and their diagnostic biomarkers in aging cells using multidisciplinary approach. Establishing sensitive and specific biomarkers of dynamic redox homeostasis is crucially important in the development of effective antiaging and senolytic interventions. Recent years have seen tremendous advances in the understanding of redox signaling events which highlight the process of aging and age-related pathologies. A major challenge in biological aging research is developing reliable biomarkers to determine the consequences of disrupted redox signaling networks long before the clinical diagnosis of age-related diseases is made. Therefore, we have chosen to concentrate on aging-induced aberrant redox signaling networks, their biomarkers, and pathological consequences in this book. Although oxidation is a natural metabolic process, the imbalance in the level of oxidants and antioxidants causes oxidative stress and eventually leads to inflammatory conditions, diabetes, neurodegenerative diseases, and cancer. Novel redox-sensitive biomarkers for the evaluation of aging-induced proteinopathies such as amyloid ss and tau proteins in Alzheimer's disease, -synuclein in Parkinson's disease, and islet amyloid polypeptides in type 2 diabetes mellitus recently drew the attention of researchers. Inside this textbook, readers will find comprehensive perspectives on the association between redox homeostasis and the aging process both at the molecular and clinical levels. Due to the inherent relationship between impaired metabolic activities and oxidative stress, the temporal interaction between intermediary metabolism and disturbed redox status can lead to greater susceptibility to aging-induced diseases and disorders, such as cardiovascular diseases, hypertension, and diabetes. This knowledge could be a key to continued research toward improving medication regimens such as in cancer and cardiovascular therapies, and procedural outcomes for patients. This book brings together current research evidence and knowledge on redox signaling and biomarkers in aging in chapters written by leading global experts in this rapidly evolving field. We hope that this textbook is of interest to a wide group of researchers, advanced students, scientifically curious non-specialist readers and clinicians alike.

Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. One possible explanation is that research and pharmacological management have focused on very early events in brain ischemia. New research has shown that brain ischemia and trauma elicit strong inflammatory reactions driven by both external and brain cells. The recognition of inflammation as a fundamental response to brain ischemia provides novel opportunities for new anti-inflammatory therapies. For the first time, an international body of researchers presents the latest findings about the cellular and humoral aspects of immune and inflammatory reactions in the brain. The work may have an impact on the treatment of neuroinjuries and ancillary brain diseases, and increase the understanding of the roles infections and immune reactions play in the brain milieu.

Natural killer (NK) cells have been at the forefront of immunology for two decades. During that time, a great amount of information about these cells has been obtained. They are important in antiinfectious and antitumoral defense and shape the adaptive immune response. In addition, they can act as immunoregulatory cells. In recent years, the therapeutic potential of NK cells in cancer immunotherapy has become increasingly evident. This book describes in detail current knowledge about NK cells and covers a broad range of NK cell-related topics, including those that are not frequently reviewed, e.g. NK cells and allergy or NK cells and skin diseases.

Mycotoxins are the metabolites of fungus and are reported to contaminate nearly 25% of the food produced worldwide. The mycotoxins of most significance are the aflatoxins due to their severe health implications and their prevalence in food commodities on a larger scale. Aflatoxins are produced by certain species of fungi the most prominent among which are Aspergillus flavus, A. parasiticus and A. nominous. Food commodities of African and South Asian countries are especially reported to have aflatoxins well beyond the allowable limits but due to the global trade of food commodities developed countries are also prone towards the perils of aflatoxins. Moreover, climate changes may have a substantial impact on the distribution and global prevalence of aflatoxins in the near future. The International Agency for Research on Cancer (IARC) has classified the aflatoxins as group 1 category carcinogen. Aflatoxins are also reported as teratogenic, mutagenic, growth retardant, immunosuppressant and may also cause nervous system and reproductive system disorders. Preventive approaches involving good manufacturing from "farm to fork" are the major focus of the current food industry. The aim of our book is to provide readers with the most recent data and up-to-date studies from aflatoxins research, with specific focuses on (i) the impact of aflatoxins on human health, (ii) new approaches by the researchers from different parts of the world to degrade aflatoxins and (iii) potential preventive approaches that can significantly lessen the burden of aflatoxins in food products

This edited book serves as a vital resource on the contributions of microorganisms to advances in nanotechnology, establishing their applications in diverse areas of biomedicine, environment, biocatalysis, food and nutrition, and renewable energy. It documents the impacts of microorganisms in nanotechnology leading to further developments in microbial nanobiotechnology. This book appeals to researchers and scholars of microbiology, biochemistry and nanotechnology.

This book discusses unique ion channels and transporters that are located within epithelial tissues of various organs including the kidney, intestine, pancreas and respiratory tract. As the authors show, these channels and transporters play crucial roles in transepithelial ion and fluid transport across epithelia and their contribution to maintaining homeostasis. Readers will be introduced to the fundamentals of ion transport in terms of function, modelling, regulation, structure and pharmacology. This is the first of three volumes highlighting the importance of epithelial ion channels and transporters in basic physiology and pathophysiology of human diseases. This volume focuses on basic fundamentals of epithelial transport physiology. There is a range of chapters dedicated to specific aspects of epithelial ion transport and cell function. Accordingly, the authors discuss techniques used to determine epithelial function, principles of epithelia transport, polarization of epithelial cells, mathematical modelling of epithelial ion transport, protein folding of ion channels, degradation epithelial ion channels, fundamentals of epithelial sodium, potassium and chloride transport, fundamentals of bicarbonate secretion, volume regulation, and microRNA regulation of epithelial channels and transporters. Given its scope, Volume 1 offers a valuable resource for physiology students, scientists and clinicians alike.

This book provides a practical guide to the analysis of data from randomized controlled trials (RCT). It gives an answer to the question of how to estimate the intervention effect in an appropriate way. This problem is examined for different RCT designs, such as RCTs with one follow-up measurement, RCTs with more than one follow-up measurement, cluster RCTs, cross-over trials, stepped wedge trials, and N-of-1 trials. The statistical methods are explained in a non-mathematical way and are illustrated by extensive examples. All datasets used in the book are available for download, so readers can reanalyse the examples to gain a better understanding of the methods used. Although most examples are taken from epidemiological and clinical studies, this book is also highly recommended for researchers working in other fields.

This book focuses on the emerging research in the field of treatment of solid tumors or cancer with new drug delivery systems using nanotechnology. Nanotechnology has given us a good scope for development of new innovative drug delivery strategies to increase the therapeutic efficacy of anticancer drugs with reduced off-target side effects. Cancer is one of the main causes of death worldwide due to the limitations of classical therapies such as low solubility of active drugs, toxic side effects on healthy cells and resistance of tumor cells. These issues are partly solved by the recent development of polymeric nanoparticles, which improve drug absorption and the therapeutic index, while reducing side effects. Drug carriers must be biocompatible, biodegradable and non-immunogenic. Coupled to a ligand that has affinity for that particular cell, polymeric nanoparticles are used to target specifically malignant cells or tissues and, in turn, improve drug stability. This book presents the latest advances in the application of polymeric particles for cancer treatment, with focus on the tumor microenvironment, synthesis, active and passive targeting, patents, targeting over-expressed receptors, tumor-targeting ligands, theranostics, glioblastoma tumors, lung cancer, breast cancer, prostate cancer and pH-responsive nanoparticles

This book contains a comprehensive series of reviews on the calcitonin gene-related peptide (CGRP) family of peptides. This family of peptide hormones has a diverse and constantly expanding range of important physiologic functions, including regulation of blood calcium, vascular tension, feeding behavior and pain recognition.

This volume includes chapters on:

• The adrenomedullin peptides and signalling
• Ligand binding and activation of the CGRP receptor
• Understanding amylin receptors
• The CGRP-receptor component protein
• The calcitonin peptide family
• Genetic regulation of CGRP
• Vascular actions of CGRP and adrenomedullin
• Intermedin/adrenomedullin 2 function
• CGRP and adrenomedullin as pain-related peptides
• Amylinergic control of ingestive behaviour
• Calcitonin receptors

This book discusses their receptors, physiological and pathophysiological functions and potential as clinical targets. It will appeal to researchers who study any of these peptides and those with an interest in migraine therapy due to the involvement of CGRP in this disorder. The book is unique because it brings together research on the whole peptide family for the first time in several years. It will be a useful reference volume for researchers in this area. This book will also appeal to researchers in the broader field of bioactive peptides.

This second edition offers 88 chapters divided among three volumes providing the most comprehensive source of know-how in the wide-ranging field of Mitochondrial Medicine. Volume III guides readers through chapters on intercellular mitochondrial transfer, Cytoplasmic transfer methods, Ndufs4 knockout mouse, in vivo assessment of mitochondrial oxygen consumption, mitochondrial network analysis by imaging, mitochondrial respiration in platelets, Heterologous Inferential Analysis (HIA), bioenergetic profiling, integrative methods for studying cardiac energetics, and isolation and deep sequencing of mitochondrial DNA.Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, application details for both the expert and non-expert reader, and tips on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Mitochondrial Medicine, Second Edition, Volume 3: Manipulating Mitochondria and Disease- Specific Approaches aims to be a comprehensive source of know-how in the wide-ranging field of Mitochondrial Medicine.

Whether you are new to literature reviews or working with new types of data, this book takes the guesswork out of writing your literature review. From deciding how much literature to include to managing your data, assessing your sources, and writing results, it outlines a step-by-step process that works with any data. To help you choose best approach for your research, this book includes: * Worksheets and decision aids to help you plan and organise your literature review * Worked examples and case studies to show you what - and what not - to do in practice * Troubleshooting tips and answers to all your frequently asked questions * Online access to a literature review starter template, an exercise workbook, project diary template, and a source credibility checklist. The perfect project support for any social sciences student, this edition also includes a new chapter on analysing mixed methods research.

This fully updated book explores all-new and revised protocols involving the use of in silico models, particularly with regard to pharmaceuticals. Divided into five sections, the volume covers the modeling of pharmaceuticals in the body, toxicity data for modeling purposes, in silico models for multiple endpoints, a number of platforms for evaluating pharmaceuticals, as well as an exploration of challenges, both scientific and sociological. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and implementation advice necessary for successful results. Authoritative and comprehensive, In Silico Methods for Predicting Drug Toxicity, Second Edition aims to guide the reader through the correct procedures needed to harness in silico models, a field which now touches a wide variety of research specialties.

This book walks you step-by-step through the whole research process so you can get up to speed understanding and doing your own research. In their friendly, down to earth style, the authors lay the theoretical foundations you need to consume and critique research, before showing how to translate this into action when tackling your own literature review or research project. This second edition: Draws on a wealth of examples from midwifery, four fields of nursing including mental health nursing and child nursing, and a range of health care specialities. Covers new and updated NMC professional education standards and maps all relevant policy and law. Supports your learning with reflective exercises, online activities and quizzes that enable you to be confident in your understanding and develop your thinking. Whether you're encountering research and evidence-based practice for the first time or refreshing your methods knowledge, this is the ideal research companion for nurses and midwives pre-registration, post-registration and beyond.

Colorectal cancer (CRC) is a major global health challenge as the third leading cause for cancer related mortalities worldwide. Despite advances in therapeutic strategies, the five-year survival rate for CRC patients has remained the same over time due to the fact that patients are often diagnosed in advanced metastatic stages. Drug resistance is another common reason for poor prognosis. Researchers are now developing advanced therapeutic strategies such as immunotherapy, targeted therapy, and combination nanotechnology for drug delivery. In addition, the identification of new biomarkers will potentiate early stage diagnosis. This book is the first of three volumes on recent developments in colorectal diagnosis and therapy. Each volume can be read on its own, or together. Each volume focuses on different novel therapeutic advances, biomarkers, and identifies therapeutic targets for treatment. Written by leading international experts in the field, coverage also addresses the role of diet habits and lifestyle in reducing gastrointestinal disorders and incidence of CRC. Chapters discuss current and future diagnostic and therapeutic options for colorectal cancer patients, focusing on immunotherapeutic, nanomedicine, biomarkers, and dietary factors for the effective management of colon cancer.

Studies of developmental biology are now benefiting the advancements made in the field of regenerative medicine. Current research on aging will attempt to reverse visible aging characteristics of somatic cells using cellular reprogramming to by-pass senescence. Medical Advancements in Aging and Regenerative Technologies: Clinical Tools and Applications aims to translate basic science discoveries into regenerative therapies with the application of clinical tool in aging and tissue regeneration. The understanding of the characteristics affecting the aging process is an effort to guide approaches for preventing and treating age-related diseases.

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series which focuses on an emerging area of cancer research. In 1968, R. H. Williams first reported that elevated prostaglandin levels are present in human medullary carcinoma. Since that time, the concept that arachidonic acid metabolites may be involved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family ofbioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respectively. Cyclooxygenase products consist of diverse products such as prostaglandin E2 (PGE2), prostacyclin (PGI2) and thromboxane A2 (TXA2), whereas lipoxygenase products consist ofhydroperoxy fatty acids and mono-, di-and tri-hydroxy acids including leukotrienes, lipoxins, and epoxides. The precursor fatty acids for the cyclooxygenase and lipoxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis --the release of substrate. This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengt Samuelsson's extensive study ofthe metabolism of prostaglandins indicate that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in the vicinity oftarget tissues leading to the concept that prostaglandins are local rrormones or autocoids. Altered production, qualitative and/or quantitative, of prostaglandins and leukotrienes has been implicated in the development of a number of disease states (e. g.

The book is an update on contentious or unsettled issues concerning invasive diagnostic and therapeutic challenges in cancer and related disorders, focusing on the surgical approach. Topics include recommendations for the best practice in using the surgery safety checklist, surgical strategies in a variety of thoracic cancers, renal cell carcinoma, tumors of parathyroid glands, mesothelioma, and bariatric surgeries. The focus is on the diagnostic and therapeutic challenges of aggressive cancerous entities, choosing the most beneficial modes for optimal outcomes and patient survival. Chapters also address radioimaging and therapy outcomes in different intracranial lesions leading to severe neurological disabilities. The areas of medical practice addressed are still veiled in uncertainty, yet-unresolved pathogenetic background, and have a substantial component of empirical rather than evidence-based clinical approach. Pursuing and sharing new ideas and innovations is essential for improving the management and outcome. The book endeavors to disseminate and deliberate on the latest medical knowledge, studies, and advancements in surgical and diagnostic dealing with cancer. The book is addressed to physicians and surgeons, and all allied health care professionals engaged in patient care and therapy.

In this book the authors review the field and explore the potential role of RNAi and other RNA technologies in cardiovascular medicine and research. They highlight the impressive recent progress but also the hurdles that still must be overcome before this promising technology is finally ready for translation and clinical use.

This concise guide covers the important angles of your grant application, whether for a health research project or personal training programme, and will help you be among the successful applicants.

The author, a reviewer for grant funding organisations and internationally respected research scientist, gives you the benefit of his experience from both sides of the process in this easy-to-use, readable guide. The book takes you through the grant application process, explaining how to: Present the justification for the proposed projectDescribe the study design clearlyEstimate the financial costsUnderstand a typical review process, and how this can influence the contents of the grant application

The author provides practical advice on a range of project types (observational studies, clinical trials, laboratory experiments, and systematic reviews) to increase the chance that your application will be successful. There are also tips on what to avoid throughout the application.

With generic information about application requirements, "How to Write a Grant Application" is ideal for healthcare professionals seeking a health services or scientific grant.

β-Carboline and its derivatives have generated considerable interest in recent years for their versatile properties in chemistry and pharmacology. This is due to their ability to act as agonists to benzodiazepine receptors, hydroxy serotonin receptors, and intercalate into DNA, to inhibit CDK, Topisomerase, and monoamine oxidase enzymes. Their pharmacological properties include anxiolytic, hypnotic, anticonvulsant, antiviral, antiparasitic and antimicrobial attributes. This book provides a summary of methods for the synthesis of various natural products engineered with the diverse β-carboline scaffold and their biological evaluation.

This book aims to introduce the latest research in gut microbiota by systematically summarizing how it modulates the pathogenesis of organ injury including alimentary tract injury, liver injury, lung injury, brain injury, renal injury, heart and vascular injury, endocrine disorders, immune responses and multiple organ dysfunction syndrome (MODS) during sepsis. Gut microbiota which is recognized as a new "organ" in the body has been demonstrated to be able to regulate the homeostasis of many organs. The key role played by gut microbiota is the hotspot in biomedical research nowadays. This book provides a state-of-the-art report on recent discoveries regarding the novel insight into the mechanisms of human diseases progression. It will also offer the overall picture of the pathophysiologic roles of gut microbiota. This book is helpful for graduate students and professional researchers to get the knowledge of frontiers in both gut microbiota and organ injury.