Strategy and Statistics in Clinical Trials deals with the research processes and the role of statistics in these processes. The book offers real-life case studies and provides a practical, how to guide to biomedical R&D. It describes the statistical building blocks and concepts of clinical trials and promotes effective cooperation between statisticians and important other parties. The discussion is organized around 15 chapters. After providing an overview of clinical development and statistics, the book explores questions when planning clinical trials, along with the attributes of medical products. It then explains how to set research objectives and goes on to consider statistical thinking, estimation, testing procedures, and statistical significance, explanation and prediction. The rest of the book focuses on exploratory and confirmatory clinical trials; hypothesis testing and multiplicity; elements of clinical trial design; choosing trial endpoints; and determination of sample size. This book is for all individuals engaged in clinical research who are interested in a better understanding of statistics, including professional clinical researchers, professors, physicians, and researchers in laboratory. It will also be of interest to corporate and government laboratories, clinical research nurses, members of the allied health professions, and post-doctoral and graduate students.

Pursuing a career in biomedical research can be daunting, considering the stiffer competition and uncertain career prospects in academia. This book summarizes career advice gathered during in-depth interviews with 106 biomedical scientists who lead their own laboratories. The participating principal investigators are from 44 research institutions in 11 countries. This book is unique in that it provides a glimpse into the mindset of principal investigators. Here, the reader will learn about common thought patterns and values, as well as the range of opinions and ways of thinking to be found among a large group of active principal investigators - without having to read more than a hundred individual autobiographies. The book will benefit all PhD students who want to learn more about their supervisor's mindset in order to successfully complete their projects. It can help freshly graduated PhDs planning to pursue an academic career, and MDs contemplating a career in research, to decide whether they truly want to embark on this path. Lastly, it can offer young principal investigators a source of inspiration on how to succeed and achieve their goals.

Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast cancer patients. This comprehensive volume brings together the current knowledge from different relevant areas, including molecular mechanisms and translational aspects of drug resistance in AIs. Topics covered include research, experimental , and clinical data specifically focused on AI resistance in breast cancer. The volume will include three sections. The first section covers general knowledge about aromatase inhibitors, including regulation of aromatase genes, and structure and function of aromatase protein. The second section provides the detailed mechanisms of resistance to AIs, while the third section explores prediction of resistance and potential strategies to overcome resistance. Breast cancer is the most common female cancer and AIs significantly improve treatments outcomes compatibly to previously used endocrine treatments. However 10-15% of post-operative patients develop a relapse during adjuvant treatment with AIs; about 25-50% of the patients do not respond to AIs in neo-adjuvant or metastatic setting, and the majority of metastatic patients who initially respond develop resistance within 3 years. There is an important need to understand these mechanisms of resistance in order to develop methods of preventing or overcoming the resistance to AIs, which will ensure a more successful outcome in treating breast cancer.

Medical research has been central to biomedicine in Africa for over a century, and Africa, along with other tropical areas, has been crucial to the development of medical science. At present, study populations in Africa participate in an increasing number of medical research projects and clinical trials, run by both public institutions and private companies. Global debates about the politics and ethics of this research are growing and local concerns are prompting calls for social studies of the "trial communities" produced by this scientific work. Drawing on rich, ethnographic and historiographic material, this volume represents the emergent field of anthropological inquiry that links Africanist ethnography to recent concerns with science, the state, and the culture of late capitalism in Africa.

In recent years there have been tremendous advances in the fields of chemistry, physics and biology which have a direct impact on advances in biomaterials science. Many areas of healthcare depend upon the development of novel biomaterials. This book contains contribution from scientists who have made numerous innovative and exciting advances in the field of biomedical materials. The latest advances in the field are covered including studies of cell interactions with biomaterials. The assessment of the potential applications for the development of new biomaterials, tissue engineering and future medical devices are discussed. It will also provide an opportunity to discuss the latest developments in the field and the vision for the future. The book clearly illustrates how basic and applied research are being combined to produce novel biomaterials.

Medical research involving human subjects has contributed to considerable advancements in our knowledge, and to medical benefits. At the same time the development of new technologies as well as further globalisation of medical research raises questions that require the attention of researchers from a range of disciplines. This book gathers the contributions of researchers from nine different countries, who analyse recent developments in medical research from ethical, historical, legal and socio-cultural perspectives. In addition to reflections on innovations in science such as genetic databases and the concept of "targeted therapy" the book also includes analyses regarding the ethico-legal regulation of new technologies such as human tissue banking or the handling of genetic information potentially relevant for participants in medical research. Country and culture-specific aspects that are relevant to human medical research from a global perspective also play a part. The value of multi- and interdisciplinary analysis that includes the perspectives of scholars from normative and empirical disciplines is a shared premise of each contribution.

Cancer is a multifaceted disease and overwhelmingly increasing experimental evidence has helped us to develop a deeper understanding of the role of signal transduction cascades in cancer development and progression. Tissue microarrays and next generation sequencing technologies have assisted us to gather missing pieces of jigsaw puzzle and we now know that deregulation of spatio-temporally controlled signaling cascades play fundamental role in metastasis and resistance against wide ranging therapeutics. This book offers a balanced overview of the rapidly emerging cutting edge research in molecular oncology and good source of knowledge for established oncologists, basic and medical students and pharmaceutical industry associated R&D departments.

Limiting genome replication to once per cell cycle is vital for maintaining genome stability. Although polyploidization is of physiologically importance for several specialized cell types, inappropriate polyploidization is believed to promote aneuploidy and transformation. A growing body of evidence indicates that the surveillance mechanisms that prevent polyploidization are frequently perturbed in cancers. Progress in the past several years has unraveled some of the underlying principles that maintain genome stability. This book brings together leaders of the field to overview subjects relating to polyploidization and cancer.

Volume 54 in the internationally acclaimed "Advances in Clinical Chemistry" contains chapters submitted from leading experts from academia and clinical laboratory science. Authors are from a diverse field of clinical chemistry disciplines and diagnostics, ranging from basic biochemical exploration to cutting-edge microarray technology.

Leading experts from academia and clinical laboratory science
Volume emphasizes novel laboratory advances with application to clinical laboratory diagnostics and practical basic science studies

Animal experiments have contributed much to our understanding of mechanisms of disease and are important for determining new therapies. This volume reviews the latest research and developments in this field.

* Discusses new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

Network Science is the emerging field concerned with the study of large, realistic networks. This interdisciplinary endeavor, focusing on the patterns of interactions that arise between individual components of natural and engineered systems, has been applied to data sets from activities as diverse as high-throughput biological experiments, online trading information, smart-meter utility supplies, and pervasive telecommunications and surveillance technologies. This unique text/reference provides a fascinating insight into the state of the art in network science, highlighting the commonality across very different areas of application and the ways in which each area can be advanced by injecting ideas and techniques from another. The book includes contributions from an international selection of experts, providing viewpoints from a broad range of disciplines. It emphasizes networks that arise in nature-such as food webs, protein interactions, gene expression, and neural connections-and in technology-such as finance, airline transport, urban development and global trade. Topics and Features: begins with a clear overview chapter to introduce this interdisciplinary field; discusses the classic network science of fixed connectivity structures, including empirical studies, mathematical models and computational algorithms; examines time-dependent processes that take place over networks, covering topics such as synchronisation, and message passing algorithms; investigates time-evolving networks, such as the World Wide Web and shifts in topological properties (connectivity, spectrum, percolation); explores applications of complex networks in the physical and engineering sciences, looking ahead to new developments in the field. Researchers and professionals from disciplines as varied as computer science, mathematics, engineering, physics, chemistry, biology, ecology, neuroscience, epidemiology, and the social sciences will all benefit from this topical and broad overview of current activities and grand challenges in the unfolding field of network science.

This book presents the fundamental physics of optical interferometry as applied to biophysical, biological and medical research. Interference is at the core of many types of optical detection and is a powerful probe of cellular and tissue structure in interfererence microscopy and in optical coherence tomography. It is also the root cause of speckle and other imaging artefacts that limit range and resolution. For biosensor applications, the inherent sensitivity of interferometry enables ultrasensitive detection of molecules in biological samples for medical diagnostics. In this book, emphasis is placed on the physics of light scattering, beginning with the molecular origins of refraction as light propagates through matter, and then treating the stochastic nature of random fields that ultimately dominate optical imaging in cells and tissue. The physics of partial coherence plays a central role in the text, with a focus on coherence detection techniques that allow information to be selectively detected out of incoherent and heterogeneous backgrounds. Optical Interferometry for Biology and Medicine is divided into four sections. The first covers fundamental principles, and the next three move up successive scales, beginning with molecular interferometry (biosensors), moving to cellular interferometry (microscopy), and ending with tissue interferometry (biomedical). An outstanding feature of the book is the clear presentation of the physics, with easy derivations of the appropriate equations, while emphasizing "rules of thumb" that can be applied by experimental researchers to give semi-quantitative predictions.

Systems-level neuronal mechanisms that coordinate the temporally, anatomically, and functionally distributed neuronal activity into coherent cognitive operations in the human brain have remained poorly understood. In humans, neuronal oscillations and synchronization can be recorded non-invasively with electro- and magnetoencephalography (EEG and MEG) that have excellent temporal resolution and an adequate spatial resolution when combined with source-reconstruction methods. In this book, leading authors in the field describe how recent methodological advances have paved the way to several major breakthroughs in the observations of large-scale synchrony from human non-invasive MEG data. This volume also presents the caveats influencing analyses of synchronization. These include the non-homogeneous sensitivity of MEG to superficial cortical sources, and, most importantly, the multitude of consequences of linear mixing. Linear mixing is an immense confounder in the sensor-level analyses of synchronization, but is also present at the source level. Approaches that can be used to avoid or compensate for these issues are then discussed. Thereafter, several authors take up a number of the functional roles that large-scale synchronization has in cognition. The authors assess how the spatio-temporal and -spectral organization and strength of both local and large-scale synchronized networks are associated with conscious sensory perception, visual working memory functions, and attention. These chapters summarize several lines of research showing how the strength of local and inter-areal oscillations in both cortical and subcortical brain structures is correlated with cognitive functions. Together these data suggest that synchronized neuronal oscillations may be a systems-level neuronal mechanism underlying the coordination of distributed processing in human cognition. In line with this argument, other authors go on to describe how oscillations and synchronization are altered in clinical populations, complementing the data presented on healthy subjects. Importantly, this book includes chapters from authors using many different approaches to the analyses of neuronal oscillations, ranging from local oscillatory activities to the usage of graph theoretical tools in the analyses of synchronization. In this way the present volume provides a comprehensive view on the analyses and functional significance of neuronal oscillations in humans. This book is aimed at doctoral and post-doctoral students as well as research scientists in the fields of cognitive neuroscience, psychology, medicine, and neurosciences.

Reflecting the development of powerful new tools and high-throughput methods to analyze adenoviral particles and their interactions with host cells, the third edition of Adenovirus Methods and Protocols calls upon experts in the field to convey advances in molecular biology, genomics and proteomics, imaging, and bioinformatics. Beginning with cryo-electron microscopy, atomic force microscopy, and mass spectrometry for a high resolution image and characterization of the virion, this detailed book then continues with capsid modifications and viral-like particles as promising alternatives to classical adenovirus vectors, and the study of adenovirus in host interactions in vitro at the cellular level as well as in vivo in animal models. Finally, the volume concludes with an extensive update of the most efficient protocols to generate, amplify, and/or purify, at small and large scale, standard human Ad5 as well as non-human, chimeric, and helper-dependent adenovirus vectors. Written in the greatly 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. Comprehensive and cutting-edge, Adenovirus Methods and Protocols, Third Edition serves as an ideal guide for scientists continuing to research this highly valuable viral tool.

From the preface: "Neural Metabolism In Vivo aims to provide a comprehensive overview of neurobiology by presenting the basic principles of up-to-date and cutting-edge technology, as well as their application in assessing the functional, morphological and metabolic aspects of the brain. Investigation of neural activity of the living brain via neurovascular coupling using multimodal imaging techniques extended our understanding of fundamental neurophysiological mechanisms, regulation of cerebral blood flow in connection to neural activity and the interplay between neurons, astrocytes and blood vessels. Constant delivery of glucose and oxygen for energy metabolism is vital for brain function, and the physiological basis of neural activity can be assessed through measurements of cerebral blood flow and consumption of glucose and oxygen.... This book presents the complex physiological and neurochemical processes of neural metabolism and function in response to various physiological conditions and pharmacological stimulations. Neurochemical detection technologies and quantitative aspects of monitoring cerebral energy substrates and other metabolites in the living brain are described under the "Cerebral metabolism of antioxidants, osmolytes and others in vivo" section. Altogether, the advent of new in vivo tools has transformed neuroscience and neurobiology research, and demands interdisciplinary approaches as each technology could only approximate a very small fraction of the true complexity of the underlying biological processes. However, translational values of the emerging in vivo methods to the application of preclinical to clinical studies cannot be emphasized enough. Thus, it is our hope that advances in our understanding of biochemical, molecular, functional and physiological processes of the brain could eventually help people with neurological problems, which are still dominated by the unknowns." -- In-Young Choi and Rolf Gruetter

International biobank collaborations allow for studies with large number of subjects where generalizability of findings across populations can be investigated, which means establishing quality criteria concerning the nature of the sample, conditions of sample storage, and the adequacy of available information is of vital importance. Methods in Biobanking brings together contributions from experts in the field in order to aid in the establishment of this much needed consistency. The volume discusses how to use existing collections of biological material to answer significant questions concerning the cause of disease without violating the personal integrity of participating sample donors, the ethical issues surrounding biobanks, guidelines for the use of coding systems and the use of biocomputing and registry linkages in research projects, as well as many other key subjects. As a volume in the highly successful Methods in Molecular Biology (TM) series, this collection provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and cutting-edge, Methods in Biobanking seeks to provide scientists with the tools necessary to take advantage of the tremendous current resources of the world's biobanks and strengthen those resources for the future.

Angiogenesis is the growth of new blood vessels and is a key process which occurs during pathological disease progression. Excessive and damaging angiogenesis occurs in diseases such as cancer, diabetic retinopathies, age-related macular degeneration and atherosclerosis. In other diseases such as stroke and myocardial infarction, insufficient or improper angiogenesis results in tissue loss and ultimately higher morbidity and mortality. In this book we will begin by providing the reader with an overview of the process of angiogenesis including normal embryological development of blood vessels. The following chapters will each focus on a key angiogenic disease incorporating current scientific knowledge concerning the causes of activation of the "angiogenic switch," pathological consequences, current treatment options and future perspectives. Where appropriate, results from pre-clinical trials, novel imaging modalities and nanotechnological approaches will be incorporated into these sections. Finally, since it is now believed that the process of angiogenesis operated via different signalling mechanisms in different vascular beds, we will discuss our current understanding of this phenomenon. The target audience for this book would include researchers in all the basic sciences; post-graduate students at Universities and Institutes; pharmaceutical industries; clinicians working in vascular biology or tissue imaging; pathologists; neurologists; tumour biologists; ophthalmologists and cardiologists.

Cell-cell adhesion is fundamental for the development and homeostasis of animal tissues and organs. Adherens junctions (AJs) are the best understood cell-cell adhesion complexes. In this volume, internationally recognized experts review AJ biology over a wide range of organization; from atoms to molecules, to protein complexes, molecular networks, cells, tissues, and overall animal development. AJs have also been an integral part of animal evolution, and play central roles in cancer development, pathogen infection and other diseases. This book addresses major questions encompassing AJ biology. - How did AJs evolve? - How do cadherins and catenins interact to assemble AJs and mediate adhesion? - How do AJs interface with other cellular machinery to couple adhesion with the whole cell? - How do AJs affect cell behaviour and multicellular development? - How can abnormal AJ activity lead to disease? Valuable for both newcomers and experts in the field, this book offers a comprehensive resource for the research laboratory and a teaching tool for advanced undergraduate and graduate courses in cell and developmental biology.

In the past several years, there has been an explosion in the ability of biologists, molecular biologists and biochemists to collect vast amounts of data on their systems. This volume presents sophisticated methods for estimating the thermodynamic parameters of specific protein-protein, protein-DNA and small molecule interactions. The use of thermodynamics in biological research is used as an energy book-keeping system. While the structure and function of a molecule is important, it is equally important to know what drives the energy force. These methods look to answer: What are the sources of energy that drive the function? Which of the pathways are of biological significance?

As the base of macromolecular structures continues to expand through powerful techniques of molecular biology, such as X-ray crystal data and spectroscopy methods, the importance of tested and reliable methods for answering these questions will continue to expand as well.

* Elucidates the relationships between structure and energetics and their applications to molecular design, aiding researchers in the design of medically important molecules * Provides a "must-have" methods volume that keeps MIE buyers and online subscribers up-to-date with the latest research * Offers step-by-step lab instructions, including necessary equipment, from a global research community "

The combination of faster, more advanced computers and more quantitatively oriented biomedical researchers has recently yielded new and more precise methods for the analysis of biomedical data. These better analyses have enhanced the conclusions that can be drawn from biomedical data, and they have changed the way that experiments are designed and performed. This volume, along with the 2 previous "Computer Methods" volumes for the "Methods in Enzymology" serial, aims to inform biomedical researchers about recent applications of modern data analysis and simulation methods as applied to biomedical research.

* Presents step-by-step computer methods and discusses the techniques in detail to enable their implementation in solving a wide range of problems * Informs biomedical researchers of the modern data analysis methods that have developed alongside computer hardware *Presents methods at the "nuts and bolts" level to identify and resolve a problem and analyze what the results mean

Arterial chemoreceptors are unique structures which continuously monitor changes in arterial blood oxygen, carbon dioxide, glucose, and acid. Alterations in these gases are almost instantaneously sensed by arterial chemoreceptors and relayed into a physiological response which restores blood homeostasis. Arterial Chemoreception contains updated material regarding the physiology of the primary arterial chemoreceptor; the carotid body. Moreover, this book also explores tantalizing evidence regarding the contribution of the aortic bodies, chromaffin cells, lung neuroepithelial bodies, and brainstem areas involved in monitoring changes in blood gases. Furthermore this collection includes data showing the critical importance of these chemoreceptors in the pathophysiology of human disease and possible therapeutic treatments. This book is a required text for any researcher in the field of arterial chemoreception for years to come. It is also a critical text for physicians searching for bench-to-bedside treatments for heart failure, sleep apnea, and pulmonary hypertension.

The book is based on lectures presented on the International Summer School on Biophysics held in Croatia in September 2009. The advantage of the School is that it provides advanced training in very broad scope of areas related to biophysics contrary to other similar schools or workshops that are centered mainly on one topic or technique. In this volume, tenth in the row, the papers in the field of biophysics are presented. The topics are biological phenomena from single protein to macromolecular aggregations structure by using variant physical methods (NMR, EPR, FTIR, Mass Spectrometry, etc.). The interrelationship of supramolecular structures and their functions is enlightened by applications of principals of these physical methods in the biophysical and molecular biology context.

This concise monograph series focuses on the implementation of various engineering principles in the conception, design, development, analysis and operation of biomedical, biotechnological and nanotechnology systems and applications. Authors are encouraged to submit their work in the following core topics, but authors should contact the commissioning editor before submitting a proposal: BIoMeDIcAL DeVIceS & MATeRIALS Trauma Analysis Vibration and Acoustics in Biomedical Applications Innovations in Processing, Characterization and Applications of Bioengineered Materials Viscoelasticity of Biological Tissues and Ultrasound Applications Dynamics, and Control in Biomechanical Systems Clinical Applications of Bioengineering Transport Phenomena In Biomedical Applications Computational Modeling and Device Design Safety and Risk Analysis of Biomedical Engineering Modeling and Processing of Bioinspired Materials and Biomaterials NANoMeDIcAL DeVIceS & MATeRIALS Bio Nano Materials Nano Medical Sciences Materials for Drug & Gene Delivery Nanotechnology for Central Nervous System Nanomaterials & Living Systems Interactions Biosensing, Diagnostics & Imaging Cancer Nanotechnology Micro & Nano Fluidics Environmental Health & Safety Soft Nanotechnology & Colloids

In this book, leading international experts analyze state-of-the-art advances in gene transfer vectors for applications in inherited disorders and also examine the toxicity profiles of these methods. The authors discuss the strengths and weaknesses of available vectors in the clinical setting, and specifically focus on the challenges and possible solutions that researchers are testing in order to improve the safety of gene therapy for genetic diseases. This comprehensive and authoritative overview of vector development is a necessary text for researchers, toxicologists, pharmacologists, molecular biologists, physicians, and students in these fields.