This volume explores the myriad of techniques and methodological approaches that are being used in breast cancer research. The authors critically evaluate of the advantages and disadvantages of current methodologies, starting with the tools available for understanding the architecture of the human breast, including its tissue and cellular composition. The volume discusses the importance of functional studies in breast cancer research, especially with the help of laser capture microdissection, which allows the separation of small amounts of tissue, as well as specific cells, for biochemical analysis. In addition, the authors address methodologies including stem cell separation, which has helped in significantly understanding their role in normal breast development, but also further the understanding of breast cancer and its therapeutic management. The use of in vitro techniques and established cell lines for mechanistic studies in chemotherapeutic approaches have been invaluable will be discussed. Imaging techniques for evaluating in vitro and in vivo behavior of normal and cancerous breast tissue will be explored, as it provides a better understanding of the physiopathology of cancer. The volume will also discuss the molecular analysis of gene function in breast cancer through the transcriptomic and epigenomic profile. More importantly, the advancement of more refined techniques in sequencing will be covered. This monograph will be a comprehensive, authoritative and timely, as it addresses the emerging approaches used in breast cancer research.

When we worked on Down Syndrome brain in the past we have been focus ing on adult brain. This was a major step forwards as most work on Down Syndrome was carried out on fibroblasts or other tissues and, moreover, we introduced proteomics to identify and quantify brain protein expression. We considered evaluation of brain protein expression in Down Syndrome brain by and by more important than gene hunting at the nucleic acid level realiz ing the long unpredictable way from RNA to protein. The availability of fetal samples along with the proteomic appproach stimulated and reinforced studies on Down Syndrome brain. And indeed, it was found out that some observations on aberrant protein expression in adult Down Syndrome brain could not be verified in the fetal samples indi cating that neurodegeneration in adult Down Syndrome brain may have been responsible rather than trisomy 21. Using brains from the early second trimester of gestation led to the generation of a series of clues for the under standing of aberrant wiring of the brain in Down Syndrome and enabled the determination of altered key functions in early life; e. g. undetectably low drebrin was observed in Down Syndrome cortex, an integral constituent and marker for dendritic spines, main effectors of cross-talk between neurons. In addition, evaluation of the nature of the neuronal deficits in terms of neuro transmission markers could be established as well as neuronal density in fetal Down Syndrome cortex."

This textbook integrates important mathematical foundations, efficient computational algorithms, applied statistical inference techniques, and cutting-edge machine learning approaches to address a wide range of crucial biomedical informatics, health analytics applications, and decision science challenges. Each concept in the book includes a rigorous symbolic formulation coupled with computational algorithms and complete end-to-end pipeline protocols implemented as functional R electronic markdown notebooks. These workflows support active learning and demonstrate comprehensive data manipulations, interactive visualizations, and sophisticated analytics. The content includes open problems, state-of-the-art scientific knowledge, ethical integration of heterogeneous scientific tools, and procedures for systematic validation and dissemination of reproducible research findings.Complementary to the enormous challenges related to handling, interrogating, and understanding massive amounts of complex structured and unstructured data, there are unique opportunities that come with access to a wealth of feature-rich, high-dimensional, and time-varying information. The topics covered in Data Science and Predictive Analytics address specific knowledge gaps, resolve educational barriers, and mitigate workforce information-readiness and data science deficiencies. Specifically, it provides a transdisciplinary curriculum integrating core mathematical principles, modern computational methods, advanced data science techniques, model-based machine learning, model-free artificial intelligence, and innovative biomedical applications. The book's fourteen chapters start with an introduction and progressively build foundational skills from visualization to linear modeling, dimensionality reduction, supervised classification, black-box machine learning techniques, qualitative learning methods, unsupervised clustering, model performance assessment, feature selection strategies, longitudinal data analytics, optimization, neural networks, and deep learning. The second edition of the book includes additional learning-based strategies utilizing generative adversarial networks, transfer learning, and synthetic data generation, as well as eight complementary electronic appendices. This textbook is suitable for formal didactic instructor-guided course education, as well as for individual or team-supported self-learning. The material is presented at the upper-division and graduate-level college courses and covers applied and interdisciplinary mathematics, contemporary learning-based data science techniques, computational algorithm development, optimization theory, statistical computing, and biomedical sciences. The analytical techniques and predictive scientific methods described in the book may be useful to a wide range of readers, formal and informal learners, college instructors, researchers, and engineers throughout the academy, industry, government, regulatory, funding, and policy agencies. The supporting book website provides many examples, datasets, functional scripts, complete electronic notebooks, extensive appendices, and additional materials.

This volume describes state-of-the-art protocols that serve as "recipes" for scientists concentrating on fibrosis research. This book is divided into four sections. Part I focuses on animal models of fibrosis and covers topics such as mimicking fibrosis in the lungs, skin, liver and heart, and generating transgenic mouse models. Part II discusses cell culture systems, where the chapters explore cell types important for the development of fibrosis. Part III looks at the purification, quantification, and analysis of the ECM proteins, and Part IV describes computer-assisted methods such as quantifying fibrillar collagen alignment and exploring the nano-surface of collagen with atomic force microscopy (AFM). Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and practical, Fibrosis: Methods and Protocols is a valuable resource aimed at outstanding quality and repeatability of research experiments in the fibrosis field.

This book gives an overview of therapeutic drug monitoring (TDM) and its clinical application. It also highlights recent advances in toxicological studies, as they relate to therapeutic drug monitoring. This is one of the few books available on the market that covers TDM. Therapeutic drug monitoring (TDM) is a clinical decision-making tool that enables dosage regimen adjustments based on clinical and laboratory measurements. TDM not only involves the measuring of drug concentrations but also interpretation of the results. There is a strong correlation between drug concentrations in body fluids and outcome than between dose and outcome. The chapters include coverage of analytical techniques, pharmacokinetics, therapeutic indices, artificial intelligence and recent advances in toxicological studies. The book fills a gap in published literature and provides reliable information on; Analytical techniques in TDM and clinical toxicology TDM and pharmacokinetic studies TDM of drugs with narrow therapeutic indices Artificial intelligence in TDM and clinical toxicology Future directions and challenges

This book summarizes the recent advances for the understanding of circadian clock system in the regulation of drug metabolism and pharmacokinetics. Basic knowledge in the field of circadian clock and pharmacokinetics are systemically introduced to make it easier for readers to understand the entire book's contents. The rhythmic expression of DMEs (drug-metabolizing enzymes) and transporters are summarized, and the underlying mechanisms thereof (i.e., regulation by circadian oscillators) are discussed. Typically, evidence for the DME- and transporter-mediated chronopharmacokinetics, chronotoxicity and chronoefficacy are highlighted in this book.

Atherosclerosis is a degenerative process affecting blood vessels, which determines narrowing of the lumen, plaque growth, and hardening of the walls. It is a risk factor for cardiovascular diseases. The focus of this book is on the management of the atherosclerotic disease. The coverage of this book spans from histological presentation of the various stages of atherosclerotic lesions to the earliest studies in atherosclerosis therapy, from advanced clinical diagnosis to monitoring, follow-up, and home-care of the atherosclerotic patient. The book shows well-established diagnostic techniques covering several medical imaging modalities such as Ultrasounds, IVUS, MRI, Computer Tomography, along with new trends in early and advanced atherosclerosis diagnosis (innovative drugs and tissue characterization procedures). Surgical standards will be presented along with innovative experimental trials for the treatment of the atherosclerotic patient. The book will also cover emerging techniques based on molecular imaging and vibro-acoustics.

Translating research into practice involves creating interventions that are relevant to improving the lives of a target population. Community engaged research has emerged as an evidence-based approach to better address the complex issues that affect the health of marginalized populations. Written by leading community-engaged researchers across disciplines, each chapter covers a different topic with comprehensive guides for start-to-finish planning and execution. The book provides a training curriculum that supports a common vision among stakeholders as well as a survey of methods based on core MPH curriculum. Practical appendices and homework samples can be found online. Public Health Research Methods for Partnerships and Practice will appeal to researchers and practitioners in community or government sectors interested in conducting community-engaged work.

A significant improvement in the safety of modern vaccines has been the development of subunit vaccines, as these are composed of very well-defined and highly pure components, often recombinant proteins. However, since protein-based antigens in general are weakly immunogenic by themselves, co-administration of adjuvants is required to induce potent and persistent specific immune responses. In recent years, there has been substantial progress in the discovery of new efficient adjuvants for subunit vaccines that are often classified into delivery systems and immunopotentiating compounds that constitute pathogen-associated molecular patterns, such as the toll-like receptor ligands. The combination of delivery systems and immunopotentiators has appeared to represent extraordinarily good adjuvants due to concomitant enhanced antigen delivery and potent stimulation of innate immunity. Many of these adjuvants are of a particulate nature and mimic the structure and/or composition of microbes in a reductionist fashion. Examples are liposomes, polymeric nanoparticles, emulsions and virus-like particles. However, there are a substantial number of pharmaceutical challenges associated with the subunit vaccine development process due to the complex nature of the antigen-adjuvant combinations. These challenges will be presented and discussed in this book. The objective of the book is to compile the concepts essential for the understanding of the pharmaceutical science and technology associated with the delivery of subunit vaccines. The books goal is to provide a comprehensive overview of the scientific and regulatory challenges facing scientists who research and develop subunit vaccines. The scope of the book is wide. It is written in a manner that will enlighten newcomers to the field (e.g., PhD students or experienced scientist switching fields) yet provide an in-depth knowledge that would benefit a skilled worker in the field. "

This monograph, written by well renowned breast cancer expect, Dr. Jose Russo, provides new insight on the pathobiology of breast cancer from the most current advances in the field, translational research, initiation and progression of the disease, the mechanism of invasion and metastasis and the concept of stem cells in treatment and drug resistance. The role of personalized medicine and genomic testing are also explored, which will provide a window to the future progress of cancer care.

This book introduces readers to the methods, types of data, and scale of analysis used in the context of health. The challenges of working with big data are explored throughout the book, while the benefits are also emphasized through the discoveries made possible by linking large datasets. Methods include thorough case studies from statistics, as well as the newest facets of data analytics: data visualization, modeling and simulation, and machine learning. The diversity of datasets is illustrated through chapters on networked data, image processing, and text, in addition to typical structured numerical datasets. While the methods, types of data, and scale have been individually covered elsewhere, by bringing them all together under one "umbrella" the book highlights synergies, while also helping scholars fluidly switch between tools as needed. New challenges and emerging frontiers are also discussed, helping scholars grasp how methods will need to change in response to the latest challenges in health.

In addition to its metabolic and endocrinologic effects, obesity and adipose tissue have now been shown to be associated with low grade inflammation resulting in cellular and humoral inflammatory factors of which the latter may act by endocrine, paracrine and autocrine mechanisms. These inflammatory mediators have increasingly been suggested as contributing to the obesity link to carcinogenesis and cancer promotion.

This volume of Energy Balance and Cancer will focus on recent developments and cutting edge research pointing to inflammation and inflammatory factors as key mediators of this linkage. The volume first provides information on inflammation as an important link between obesity and insulin resistance, which is in itself linked to promotion of cancer through hyperinsulinemia. The volume then covers some of the most important mechanisms by which obesity leads to inflammation, including the novel inflammasome concept, alterations in chromatin structure, circulating inflammatory factors, unique cellular interactions between adipocytes and macrophages and the direct link of dietary fat to inflammation and cancer.

Overall, this volume will provide important insight to help understand how inflammation may help modulate the linkage between obesity and cancer and serve as a platform for developing future research in this area.

This detailed volume presents timely and authoritative content offering a comprehensive overview of the current state of the art in fungal diagnostics. Moreover, it addresses on-going developments expected to provide a basis for targeted treatment strategies resulting in improved outcome of invasive mycoses. The knowledge of host-related predisposing factors and stratified treatment options facilitating timely onset of adequate antifungal therapy are critical for successful clinical management and outcome of invasive fungal disease (IFD), requiring not only rapid diagnosis of a fungal infection and identification of the causative species, but also assessment of pathogen/host factors related to pathogenicity, susceptibility, and response to treatment. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Human Fungal Pathogen Identification: Methods and Protocols serves as an ideal reference for researchers investigating the ever-growing worldwide healthcare problems involving fungal infections.

Adopting a proactive approach and focusing on emerging radiation-generating technologies, "Health Physics in the 21st Century" meets the growing need for a presentation of the relevant radiological characteristics and hazards. As such, this monograph discusses those technologies that will affect the health physics and radiation protection profession over the decades to come.

After an introductory overview, the second part of this book looks at fission and fusion energy, followed by a section devoted to accelerators, while the final main section deals with radiation on manned space missions. Throughout, the author summarizes the relevant technology and scientific basis, while providing over 200 problems plus solutions to illustrate and amplify the text.

Twelve appendices add further background material to support and enrich the topics addressed in the text, making this invaluable reading for students and lecturers in physics, biophysicists, clinical, nuclear and radiation physicists, as well as physicists in industry.

Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.

Qualitative researchers have traditionally been cautious about claiming that their work was scientific. The "right-on" schools have exaggerated this caution into an outright rejection of science as a model for their work. Science is, for them, outmoded; "an archaic form of consciousness surviving for a while yet in a degraded form" ("Tyler 1986:200"). Scientists' assertions that they are in pursuit of truth simply camouflage their own lust for power. There is no essential difference between truth and propaganda. The authors acknowledge that the boundary between science and propaganda has often been breached and some distrust of scientific claims may be healthy. They also question the claim that science creates disinterested and objective knowledge of an observer-independent world without concluding that science is impossible. The skeptics' reservations about qualitative research are based on the deep-rooted assumption among natural scientists, and some social scientists, that there is a world "out there," prior to, and independent of, their observations. This world can be known objectively in the sense that all observers will, if identically placed, see it in exactly the same way. If a suitable language were available, they would also all produce identical descriptions. From these observations they can work out the laws governing the world's operations. The authors try to resolve these contrary claims by asserting that science is a "procedural" commitment. It consists of openness to refutation, a conscientious and systematic search for contradictory evidence, and a readiness to subject one's preconceptions to critical examination. The devotion to truth as a regulative ideal is an essential difference between science and propaganda. This work is a unique and innovative defense of scientific method. "Elizabeth Murphy" is reader in sociology and social policy at the University of Nottingham, UK. "Robert Dingwall" is professor and director of the Institute for the Study of Genetics, Biorisks, and Society at the University of Nottingham, UK.

This book focuses on the envelope of Gram-positive bacteria including its composition, the latest discoveries in the mechanisms behind its assembly, and its role in pathogenesis. Furthermore, new applications in biotechnology and vaccine development involving these bacteria are discussed in detail. This concise volume consists of eleven chapters by prominent experts in the field, which review the latest findings and current state of knowledge on a range of diverse yet interlinked aspects. This book is written for all researchers, clinicians and technicians engaged in basic or applied science projects on Gram-positive bacteria.

This volume explores the application of Quality by Design (QbD) to biopharmaceutical drug product development. Twenty-eight comprehensive chapters cover dosage forms, liquid and lyophilized drug products. The introductory chapters of this book define key elements of QbD and examine how these elements are integrated into drug product development. These chapters also discuss lessons learned from the FDA Office of Biotechnology Products pilot program. Following chapters demonstrate how QbD is used for formulation development ranging from screening of formulations to developability assessment to development of lyophilized and liquid formats. The next few chapters study the use of small-scale and surrogate models as well as QbD application to drug product processes such as drug substance freezing and thawing, mixing, sterile filtration, filling, lyophilization, inspection and shipping and handling. Later chapters describe more specialized applications of QbD in the drug product realm. This includes the use of QbD in primary containers, devices and combination product development. The volume also explores QbD applied to vaccine development, automation, mathematical modeling and monitoring, and controlling processes and defining control strategies. It concludes with a discussion on the application of QbD to drug product technology transfer as well as overall regulatory considerations and lifecycle management. Quality by Design for Biopharmaceutical Drug Product Development is an authoritative resource for scientists and researchers interested in expanding their knowledge on QbD principles and uses in creating better drugs.

Cardiovascular immunology is a newly emerging research area, investigating the crosstalk between the cardiovascular and the immune system. This crosstalk is evident through (1) crucial immunological capacities and functions of cardiovascular cell types, including cardiomyocytes, fibroblasts, endothelial cells, pericytes and cardiac resident macrophages, (2) the impact of aberrant immune function on the development of cardiovascular disease such as atherosclerosis, direct and indirect immune-mediated heart disease and vasculitis, and (3) the crucial role of the immune system in cardiac repair and regeneration. The Immunology of Cardiovascular Homeostasis and Pathology covers all these aspects of cardiovascular immunology, starting with homeostatic immunological functions of traditional cardiovascular cell types, and moving then to the role of the immune system in cardiovascular pathology and to recent research into targeting the immune system to boost cardiac healing and regeneration.

Achieving good clinical outcomes with implanted biomaterials depends upon achieving optimal function, both mechanical and biological, which in turn depends upon integrating advances realized in biological science, material science, and tissue engineering. As these advances push back the frontiers of biomaterial medicine , the control and patterning of bio-implant interface reactions will have a tremendous impact on future design and prospects of implant treatments.

Bio-Implant Interface: Improving Biomaterials and Tissue Reactions brings together a remarkable panel of scientists to present the state of the art in our understanding of interactions at the interface between biomaterials and living tissue. Much of the focus is on the importance of the implant surface's topography and chemistry to its interaction with the biological environment. Biomineralization along with the biological content of the interface and its role in directing cellular response along desired pathways also receive particular attention.

The pursuit of new and better designs for improved biocompatibility and patient response to implants continues to challenge clinicians and scientists alike. This book offers a unique opportunity to bring yourself up to date on recent advances in the field and new strategies for controlling the bio-implant interface.

F. Macfarlane Burnet I have been an interested onlooker for many years at research on the biology of trace elements, particularly in its bearing on the pas toral and agricultural importance of copper, zinc, cobalt, and mo lybdenum deficiencies in the soil of various parts of Australia. More recently I have developed a rather more specific interest in the role of zinc, particularly in relation to the dominance of zinc metalloenzymes in the processes of DNA replication and repair, and its possible significance for human pathology. One area of special significance is the striking effect of zinc deficiency in the mother in producing congenital abnormalities in the fetus. The fact that several chapters in the present work are concerned with this and other aspects of zinc deficiency is, I fancy, the editors jus tification for inviting me to write this foreword. In reading several of the chpaters before publication, my main impression was of the great potential importance of the topic of trace metal biology in both its negative and positive aspects-the effects of deficiency of essential elements and the toxicity of such pollutants of the modern world as lead or mercury mainly as or ganic compounds."

This book highlights the latest advances in the application of artificial intelligence to healthcare and medicine. It gathers selected papers presented at the 2019 Health Intelligence workshop, which was jointly held with the Association for the Advancement of Artificial Intelligence (AAAI) annual conference, and presents an overview of the central issues, challenges, and potential opportunities in the field, along with new research results. By addressing a wide range of practical applications, the book makes the emerging topics of digital health and precision medicine accessible to a broad readership. Further, it offers an essential source of information for scientists, researchers, students, industry professionals, national and international public health agencies, and NGOs interested in the theory and practice of digital and precision medicine and health, with an emphasis on risk factors in connection with disease prevention, diagnosis, and intervention.

A wide range of research methods for the study of vascular development, from basic laboratory protocols to advanced technologies used in clinical practice, are covered in this work. A range of methodologies such as molecular imaging platforms and signalling analysis, along with tumour models are collated here. Four sections explore in vitro techniques, in vivo and ex vivo manipulations, imaging and histological analysis and other novel techniques in vascular biology. Readers will discover basic methodologies used for analysis of endothelial cell growth in vitro, including co-culture models of vessel formation. Authors also explore isolation and purification of cells and methods for analysis of data and visualization of localized vasculature with modern imaging platforms. Both animal models and human disease are covered in this work. Each chapter contains helpful sections on trouble shooting, additional notes and links, supporting the reader to carry out protocols. This book will appeal to students, researchers and medical professionals working in all vascular-linked fields such as cardio- and cerebrovascular, cancer and dementia.

"No doctor, however great his capacity or original his ideas, has the right to choose martyrs for science or for the general good." Human Guinea Pigs: Experimentation on Man.Whistle-blowers tend not to be very popular. Maurice Pappworth's whistle was in the form of Human Guinea Pigs, the controversial book published in 1967 which examined unethical medical experimentation on humans and identified the researchers and institutions responsible. The ground-breaking text took the medical establishment by storm and provoked questions in Parliament. Brilliant, Jewish, already an outsider, Pappworth was recognised as the best medical teacher in the country. But convinced that the reason for these experiments being carried out was purely to advance the careers of ambitious practitioners, Pappworth had to speak up. In the wake of his expose, stricter codes of practice for human experimentation were put into place and the establishment of the research ethics committees was formed, which remains in place today. Maurice Pappworth's daughter, the late Joanna Seldon, re-assesses the importance of Human Guinea Pigs in her book Whistle-blower: The Life of Maurice Pappworth. She considers her father's text a major milestone in the development of current medical research ethics and demands a re-evaluation of the pioneering medical ethicist who compromised his own career in order to ensure the protection of the patient.

In anticipation of the opening of the H. Lee Moffitt Cancer Center and Research lnstitut on the campus of the University of South Florida, an international symposium, "The First Annual H. Lee Moffitt Symposium on Cancer Biology and Therapeutics" was held in Tampa, Florida on January 20-22, 1986. In this first symposium we decided to present a broad-based series of topics dealing with the major issues in the field of cancer. These topics ranged from the biochemistry of the cancer cell to the design of antineoplastic agents, through tumor cell heterogeneity, treatment of ltuman neoplasms to immunological aspects of cancer biology and tr atment. The speakers chosen represented individuals of international acclaim who are very active in the area of cancer research and treatment. The symposium brought together scien tists/physicians from six nations including Austria, Canada, France, Hungary, West Germany, and of course, the United States. The congeniality of the participants promoted the friendly exchange of knowledge which, it is hoped, will greatly hasten the time when successful management of human cancer will become routine. Future symposia in this series will be highly focused and will deal with a single facet of this vast field of cancer research and treatment. Joseph G. Cory, Editor Andor Szentivanyi, Editor University of South Florida, 1986 V ACKNOWLEDGMENTS This volume presents the Proceedings of the H. Lee Moffitt International Syn osium on Cancer Biology and Therapeutics which was held in Tampa, Florida on January 20, 21, and 22, 1986."