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

Microbial infection is increasingly seen as a problem as we begin to run out of antibiotics. Understanding how microbes cause disease is essential. In recent years it has begun to emerge that bacteria, fungi, protozoa and viruses can use their cell stress proteins to cause infection. This volume brings together the world's leading experts in the study of the microbial and human cell stress proteins that are involved in enabling microorganisms to infect humans and cause serious disease.

Coherent treatment of a variety of approaches to multiple comparisons Broad coverage of topics, with contributions by internationally leading experts Detailed treatment of applications in medicine and life sciences Suitable for researchers, lecturers / students, and practitioners

This book is devoted to the problems of oxidation chemical reactions and addresses bimodal reaction sequences. Chemical reactions of oxidation, occurring under certain conditions and in multicomponent systems are complex processes. The process of the oxidation essentially changes in the presence and contact of the solid substances with reactants. The role of solid substances and the appearance of this phenomenon in oxidation reaction are discussed. The reader will understand the "driving forces" of this phenomenon and apply it in practice. Written for chemists, physicists, biologists and engineers working in the domain of oxidation reactions. Key Selling Features: Covers the historical background, modern state of the art, and perspectives in investigations of the coupling between heterogeneous and homogeneous reactions Discusses the feasible pathways of the coupling of heterogeneous and homogeneous reactions in oxidation in man-made and natural chemical systems Addresses the abundance, peculiarities and mechanisms of the bimodal reaction sequences in oxidation with dioxygen in recent decades Discusses the existence of the bimodal reaction sequences in chemical systems investigations in atmospheric chemistry and heterogeneous photocatalysis Presented in a simple concise style, accessible for both specialists and non-specialists

A highly practical guide to public health intervention development. This book has been developed to assist anyone involved with effective health promotion project design. It cuts through the complex theories and technical frameworks to provide a 6 step formula for creating effective and sustainable interventions. Key features Adopts a pragmatic approach that addresses barriers and challenges to project delivery Utilises the Six Steps in Quality Intervention Development framework - a unique model designed specifically to improve intervention planning Combines the theory and concepts behind intervention development with practical methods of delivery on the ground Includes detailed case studies that provide examples of how the six steps can be used for successful intervention design As the health needs of an increasingly globalised world continue to evolve and shift, effective planning and intervention work will only become more important. Written by leading researchers and experts who draw on a wealth of experience in the field, this book will be essential reading for any student, practitioner or policy maker requiring an understanding of practical intervention design.

Drug Discovery with Privileged Building Blocks traces back PharmaBlock's founding philosophy of designing privileged building blocks. High-quality building blocks are crucial not only to biological activities of different molecules but also to ADMET properties, which eventually will impact the success rate of drug discovery projects. A thorough study of how building blocks perform in drug molecules and a regular analysis of new building block structures in the latest researches have proven to be a fruitful strategy to generate novel building blocks. Using this strategy, PharmaBlock has supplied the drug industry with a great number of building blocks, which are increasingly being adopted by drug hunters, and these are identified in this book. Each chapter may be read and studied without learning the previous chapters. This book will be a good starting point for novice medicinal chemists, and veteran medicinal chemists will find it useful as well. Key Feature The book covers privileged building blocks appearing most frequently on patents for novel drugs. The latest relevant tactics are explained in the context of drug design and medicinal chemistry. Key synthesis, especially large-scale synthesis, is described. The most recent literature references are cited.

Drug Discovery with Privileged Building Blocks traces back PharmaBlock's founding philosophy of designing privileged building blocks. High-quality building blocks are crucial not only to biological activities of different molecules but also to ADMET properties, which eventually will impact the success rate of drug discovery projects. A thorough study of how building blocks perform in drug molecules and a regular analysis of new building block structures in the latest researches have proven to be a fruitful strategy to generate novel building blocks. Using this strategy, PharmaBlock has supplied the drug industry with a great number of building blocks, which are increasingly being adopted by drug hunters, and these are identified in this book. Each chapter may be read and studied without learning the previous chapters. This book will be a good starting point for novice medicinal chemists, and veteran medicinal chemists will find it useful as well. Key Feature The book covers privileged building blocks appearing most frequently on patents for novel drugs. The latest relevant tactics are explained in the context of drug design and medicinal chemistry. Key synthesis, especially large-scale synthesis, is described. The most recent literature references are cited.

The conceptual process of drug discovery is one that is often the result of an identified need in a defined disease area. This need represents a mandate from the marketing department of a phar- maceutical company or a breakthrough at the research level that has agreed applicability in response to a valid therapeutic demand. Although the intelligent design and development of new thera- peutic entities, as evidenced by Sir James Black's H -receptor an- 2 tagonist cimetidine (Tagamet), is intellectually satisfying, many novel drugs arise from serendipity, from the chance observation of the research scientist or the clinician, that a compound has unex- pected actions of use for the treatment of human disease states. Drugs that have been identified by this route include the antipsy- chotic chlorpromazine and the putative anxiolytic buspirone. The events surrounding the process of drug discovery and de- velopment are the theme of the present volume, which attempts to present, in a logical and lucid manner, the complexity of a process that is often naively assumed to represent nothing more than the identification of a new compound and its rapid introduction into humans, free of such complications as efficacy, selectivity, safety, bioavailability, toxicity, and need.

Genetically-engineered mouse models for cancer research have become invaluable tools for studying cancer biology and evaluating novel therapeutic approaches. This volume focuses on state-of-the-art methods for generating, analyzing and validating such models for studying aspects of human cancer biology. Additionally, these models are emerging as important pre-clinical systems in which to test cancer prevention and therapeutic strategies in order to select compounds for testing in clinical trials.

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

This book provides a compilation of the most up-to-date literature on the topic of immediate early genes (IEGs). It reviews and details experiments and theories that challenge the reader to expand their view on how IEG research is currently being used to advance our understanding of static and active brain circuits. In addition, the book explores roles of IEGs in clinical neuropathology.

This book provides a user-friendly introduction to the qualitative methods most commonly used in the mental health and psychotherapy arena. * Chapters are written by leading researchers and the editors are experienced qualitative researchers, clinical trainers, and mental health practitioners * Provides chapter-by-chapter guidance on conducting a qualitative study from across a range of approaches * Offers guidance on how to review and appraise existing qualitative literature, how to choose the most appropriate method, and how to consider ethical issues * Demonstrates how specific methods have been applied to questions in mental health research * Uses examples drawn from recent research, including research with service users, in mental health practice and in psychotherapy

Aggregates of the TAR DNA binding protein 43 (TDP-43), are hallmark features of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD), with overlapping clinical, genetic and pathological features. TDP-43 and Neurodegeneration: From Bench to Bedside summarizes new findings in TDP-43 pathobiology and proteinopathies. The book summarizes TDP-43's structure, function, biology, misfolding, aggregation, pathogenesis and therapeutics. It includes autophagy-mediated therapy, role of stress granule, novel genetic, cell culture-based models, systems biology for precision medicine, development of stem cells and mechanism-based therapies that can target ALS and other related neurodegenerative diseases. This book is written for neuroscientists, neurologists, clinicians, advanced graduate students, drug discovery researchers, as well as cellular and molecular biologists involved in ALS, motor neuron disease (MND) and other neurodegenerative disorders.

Methodologies for Biosimilar Product Development covers the practical and challenging issues that are commonly encountered during the development, review, and approval of a proposed biosimilar product. These practical and challenging issues include, but are not limited to the mix-up use of interval hypotheses testing (i.e., the use of TOST) and confidence interval approach, a risk/benefit assessment for non-inferiority/similarity margin, PK/PD bridging studies with multiple references, the detection of possible reference product change over time, design and analysis of biosimilar switching studies, the assessment of sensitivity index for assessment of extrapolation across indications without collecting data from those indications not under study, and the feasibility and validation of non-medical switch post-approval. Key Features: Reviews withdrawn draft guidance on analytical similarity assessment. Evaluates various methods for analytical similarity evaluation based on FDA's current guidelines. Provides a general approach for the use of n-of-1 trial design for assessment of interchangeability. Discusses the feasibility and validity of the non-medical switch studies. Provides innovative thinking for detection of possible reference product change over time. This book embraces innovative thinking of design and analysis for biosimilar studies, which are required for review and approval of biosimilar regulatory submissions.

Phylogenetic presentation of medicinal plants and a chemotaxonomical rationale of antiviral, antibacterial, and antifungal action. Discusses chemical structure-activity relationship, pharmacokinetics, and oral bioavailability of antimicrobial principles Introduces the molecular mechanism of natural products on viruses, bacteria, and fungi. Contains a selection of hand-made botanical plates and useful bibliographic references A useful research tool for postgraduates, academics, and the pharmaceutical, herbal, or nutrition industries.

Phylogenetic presentation of medicinal plants and a chemotaxonomical rationale of antiviral, antibacterial, and antifungal action. Discusses chemical structure-activity relationship, pharmacokinetics, and oral bioavailability of antimicrobial principles Introduces the molecular mechanism of natural products on viruses, bacteria, and fungi. Contains a selection of hand-made botanical plates and useful bibliographic references A useful research tool for postgraduates, academics, and the pharmaceutical, herbal, or nutrition industries.

The overall themes of this book are recent advances in mechanisms of pain and the application of those in clinics. Specific attention is paid to developing countries where practice of pain management seriously lags behind current scientific understanding. Both the local traditions for curing pain and the substances used are presented in this book.

In these uncertain times, how much can you trust health news? Is the research behind breaking headlines reliable? This book is an indispensable resource for students and general readers, helping them evaluate and think critically about health information. "People Who Drink Coffee Live Longer." "Students Learn Better When Listening to Classical Music." "Scientists Discover the Gene That Causes Obesity." We are constantly bombarded with reports of "groundbreaking" health findings that use attention-grabbing headlines and seem to be backed by credible science. Yet many of these studies and the news articles that discuss them fall prey to a variety of problems that can produce misleading and inaccurate results. Some of these may be easy to notice-like a research study on the benefits of red meat funded by the beef industry, or a study with a sample size of only 10 people-but others are much harder to spot. Skewed Studies: Exploring the Limits and Flaws of Health and Psychology Research examines the most pervasive problems plaguing health research and reporting today, using clear, accessible language and employing real-world examples to illustrate key concepts. Beyond simply outlining issues, it provides readers with the knowledge and skills to evaluate research studies and news reports for themselves, improving their health literacy and critical thinking skills. Brings together and thoroughly explores the many ways in which health research and reporting can be flawed and problematic Improves readers' critical thinking skills and gives them practical tools to better evaluate the health information they come across Explains scientific and statistical concepts in clear, easy-to-understand language Includes a curated and annotated directory of resources for readers seeking additional information

In healthcare, the realisation of an optimistic prognosis against pessimistic ones depends on current innovations in diagnostic and cost-effective treatment approaches being widely adopted in clinical practice. Utilisation of advanced early and predictive diagnostics, targeted prevention and personalised medical approaches could enable the elderly subpopulation to reach the 100-year age limit in good physical and mental health, as actively contributing members of society. This task requires intelligent political regulations and creation of new guidelines to advance current healthcare systems. In this book, we will collect contributions from several geopolitical regions of Europe, Asia and USA that provide expert opinion on healthcare organisation and outlook as well as economical aspects of personalised medicine.

Medicinal Chemistry: A Look at How Drugs Are Discovered is written for those who are interested in learning how drugs are discovered. Compared to other books on the market, this text takes a different approach by presenting the subject on chemical reaction mechanism terms, which ideally makes the subject matter more interesting and easier to comprehend. The authors describe the drug discovery process, from advancing an initial lead to the approval process, and include drug discovery sources. Additional features: Explains medicinal chemistry on chemical mechanism terms, allowing for a more interesting and easier to comprehend text Includes valuable insights toward the various pathways taken at pharmaceutical industries in drug discoveries Improved by including questions raised and suggestions made from students in the authors' medicinal chemistry classes This book will benefit both upper level undergraduates and graduates studying in the fields of medicinal chemistry and drug discovery, as well as scientists working in the pharmaceutical industry.

Design and Analysis of Cross-Over Trials is concerned with a specific kind of comparative trial known as the cross-over trial, in which subjects receive different sequences of treatments. Such trials are widely used in clinical and medical research, and in other diverse areas such as veterinary science, psychology, sports science, and agriculture. The first edition of this book was the first to be wholly devoted to the subject. The second edition was revised to mirror growth and development in areas where the design remained in widespread use and new areas where it had grown in importance. This new Third Edition: Contains seven new chapters written in the form of short case studies that address re-estimating sample size when testing for average bioequivalence, fitting a nonlinear dose response function, estimating a dose to take forward from phase two to phase three, establishing proof of concept, and recalculating the sample size using conditional power Employs the R package Crossover, specially created to accompany the book and provide a graphical user interface for locating designs in a large catalog and for searching for new designs Includes updates regarding the use of period baselines and the analysis of data from very small trials Reflects the availability of new procedures in SAS, particularly proc glimmix Presents the SAS procedure proc mcmc as an alternative to WinBUGS for Bayesian analysis Complete with real data and downloadable SAS code, Design and Analysis of Cross-Over Trials, Third Edition provides a practical understanding of the latest methods along with the necessary tools for implementation.

Intellectual Property and Health Technologies

Balancing Innovation and the Public's Health

Joanna T. Brougher, Esq., MPH

At first glance, ownership of intellectual property seems straightforward: the control over an invention or idea. But with the recent explosion of new scientific discoveries poised to transform public health and healthcare systems, costly and lengthy patent disputes threaten both to undermine the attempts to develop new medical technologies and to keep potentially life-saving treatments from patients who need them.

"Intellectual Property and Health Technologies" grounds readers in patent law and explores how scientific research and enterprise are evolving in response. Geared specifically to the medical disciplines, it differentiates among forms of legal protection for inventors such as copyrights and patents, explains their limits, and argues for balance between competing forces of exclusivity and availability. Chapters delve into the major legal controversies concerning medical and biotechnologies in terms of pricing, markets, and especially the tension between innovation and access, including:

The patent-eligibility of genesThe patent-eligibility of medical process patentsThe rights and roles of universities and inventorsThe balancing of access, innovation, and profit in drug developmentThe tension between biologics, small-molecule drugs, and their generic counterpartsInternational patent law and access to medicine in the developing world

As these issues continue to shape and define the debate, "Intellectual Property and Health Technologies" enables professionals and graduate students in public health, health policy, healthcare administration, and medicine to understand patent law and how it affects the development of medical technology and the delivery of medicine. "

This easy-to-read reference book provides a practical approach for dealing with the legal and regulatory compliance issues involved in human research. Covering a broad range of topics, such as consent, confidentiality, subject recruitment and selection, the role of the investigator and Institutional Review Board, it offers timely and useful strategies for achieving regulatory compliance while reducing liability. In addition, insurance, quality management, accreditation, and risk management are topics examined in the book. The practical insights found in this volume are not found in other books on the subject. Clinical Trials and Human Research is a practical tool to help anyone involved in clinical research.

Dynamic Treatment Regimes: Statistical Methods for Precision Medicine provides a comprehensive introduction to statistical methodology for the evaluation and discovery of dynamic treatment regimes from data. Researchers and graduate students in statistics, data science, and related quantitative disciplines with a background in probability and statistical inference and popular statistical modeling techniques will be prepared for further study of this rapidly evolving field. A dynamic treatment regime is a set of sequential decision rules, each corresponding to a key decision point in a disease or disorder process, where each rule takes as input patient information and returns the treatment option he or she should receive. Thus, a treatment regime formalizes how a clinician synthesizes patient information and selects treatments in practice. Treatment regimes are of obvious relevance to precision medicine, which involves tailoring treatment selection to patient characteristics in an evidence-based way. Of critical importance to precision medicine is estimation of an optimal treatment regime, one that, if used to select treatments for the patient population, would lead to the most beneficial outcome on average. Key methods for estimation of an optimal treatment regime from data are motivated and described in detail. A dedicated companion website presents full accounts of application of the methods using a comprehensive R package developed by the authors. The authors' website www.dtr-book.com includes updates, corrections, new papers, and links to useful websites.